Immunoglobulin Research Papers - Academia.edu (original) (raw)

Modification of antibody effector functions is commonly performed by chimerization or humanization. Cloning of antibody variable regions from hybridomas represents a first step that is frequently hampered by the expression of non-functionally rearranged variable regions in hybridoma cells that originate from MOPC21-derived fusion partners. We now present a simple method to clone functionally rearranged V-genes, based on V-gene-specific multiplex PCR screening. Using this method we document the expression of aberrant V-genes that originate from the original B-cell used for the hybridoma generation, not from the fusion partner, and are-thus-hybridoma specific.

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- Immunology, Biology, Medicine, Gene expression

L'administration par voie intraveineuse d'immunoglobulines polyvalentes (Ig IV) est utilisée, depuis de nombreuses années, dans le traitement substitutif des déficits immunitaires primitifs avec défaut de production d'anticorps. Dans cette étude, nous avons évalué le devenir d'enfants atteints par ces maladies ayant reçu ce type de traitement de façon prolongée. Patients et méthodes.-Il s'agit d'une étude rétrospective évaluant les manifestations cliniques avant puis pendant le traitement par les Ig IV en fonction du taux des IgG résiduelles chez 10 enfants atteints d'agammaglobulinémie, dont 9 garçons et 1 fille. Le taux des Ig sériques a été dosé par néphélémétrie. Les lymphocytes B circulants, les lymphocytes T et les sous-populations lymphocytaires T ont été comptés en utilisant des anticorps monoclonaux. La fonction des lymphocytes T a été évaluée en utilisant des tests de prolifération induits par les mitogènes (phytohémagglutinine) et les antigènes (tuberculine, anatoxine tétanique). À chaque séance de traitement par Ig IV, l'état clinique des patients était évalué, les épisodes infectieux et le traitement antibiotique reçu notés dans le dossier médical et un prélèvement bactériologique effectué au niveau du point d'appel en cas d'infection. Résultats.-Le nombre cumulatif des mois de traitement était de 866 mois avec une durée médiane du traitement de 108 mois. Ce traitement a été systématiquement administré en moyenne 1 fois toutes les 4 semaines. La médiane des doses administrées était de 500 mg/kg par mois (300-900 mg/kg/mois). Durant le traitement par les Ig IV, les taux moyens d'IgG résiduelles par patient variaient de 2,4 à 6,2 g/l (moyenne = 3,9 g/l). Avant l'administration d'Ig IV, les patients avaient eu un total de 99 infections bactériennes à prédominance respiratoire (48,5 %). Quatre patients avaient au moment de l'instauration du traitement une dilatation des bronches. Le nombre global d'infections a été réduit à 25 pendant le traitement par les Ig IV, et le taux d'infection par patient et par année a chuté de façon significative. Un patient a eu une méningoencéphalite à Echovirus 27 durant le traitement. Conclusion.-Des taux moyens d'IgG résiduelles de 3,9 g/l ont permis de réduire la fréquence des infections bactériennes de façon significative. Le traitement des patients par Ig IV, leur mise sous antibiothérapie spécifique et les séances de kinésithérapie respiratoire ont permis une réduction importante des infections respiratoires, et la stabilisation des lésions de dilatation des bronches. En revanche, ce traitement ne protège pas des méningoencéphalites virales.

- by Fethi Mellouli
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- Medicine, Infant, Retrospective Studies, Bacterial infections

The B cell antigen receptor (BCR) comprises the membrane-bound immunoglobulin (mIg) molecule and the Ig-a/Ig-b heterodimer. By comparing the stability of the IgD-BCR and IgM-BCR in dierent detergent lysates, we ®nd that the IgD-BCR is more stable than the IgM-BCR. Analysis of chimeric mIgD molecules suggests that the dm transmembrane region is responsible for the more stable association of mIgD with the Ig-a/Ig-b heterodimer. Further, the dierential glycosylation of Iga molecules, in the two dierent BCR complexes, is determined solely by the ectodomains of the mIg molecules. The implications of these ®ndings for the intracellular transport and the signalling capacity of the BCRs are discussed.

- by Michael Reth
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- Immunology, Stability, Molecular Immunology, Endoplasmic Reticulum

In B lymphocytes, immunoglobulin (Ig)M receptors drive development and construction of naive repertoire, whereas IgG receptors promote formation of the memory B cell compartment. This isotype switching process requires appropriate B cell activation and T cell help. In the absence of T cell help, activated B cells undergo Fas-mediated apoptosis, a peripheral mechanism contributing to the establishment of self-tolerance. Using Ig -deficient MT mouse model, where B cell development is blocked at pro-B stage, here we show an alternative developmental pathway used by isotype-switched B cell precursors. We find that isotype switching occurs normally in B cell precursors and is T independent. Ongoing isotype switching was found in both normal and MT B cell development as reflected by detection of IgG1 germline and postswitch transcripts as well as activation-induced cytidine deaminase expression, resulting in the generation of IgG-expressing cells. These isotype-switched B cells are negatively selected by Fas pathway, as blocking the Fas/FasL interaction rescues the development of isotypeswitched B cells in vivo and in vitro. Similar to memory B cells, isotype-switched B cells have a marginal zone phenotype. We suggest a novel developmental pathway used by isotypeswitched B cell precursors that effectively circumvents peripheral tolerance requirements. This developmental pathway, however, is strictly controlled by Fas/FasL interaction to prevent B cell autoimmunity.

- by J. Seagal
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- Cell Differentiation, Mice, The, Mouse Model

Objectives: As international estimates of the effectiveness of post-exposure prophylaxis of measles vary, we sought to determine the effectiveness of post-exposure prophylaxis with either vaccine or immunoglobulin in susceptible persons with known measles contact. Methods: Data were obtained on all cases of measles notified in NSW between 1 March and 31 May 2006 and their contacts. The effectiveness of prophylaxis was calculated using the cohort method. Results: During March to May 2006, 57 cases of measles were notified and 1760 measles contacts were identified, of which 553 were classified as susceptible. The calculated effectiveness of post-exposure prophylaxis with vaccine or immunoglobulin in preventing measles was 83.3% (95% CI: 27-96%). Conclusion: Post-exposure immunisation remains an effective tool for preventing secondary cases of measles.

- by Vicky Sheppeard and +1
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- Nursing, Government, Health, Public Health

Objective. Blood platelets represent a link between hemostasis, inflammation, and tissue repair. Their role in immune responses and inflammation mainly involves many molecules, among which Toll-like receptor, major histocompatibility complex class I, CD40 and CD154/CD40 ligand (CD40L). As platelets are the major purveyor of soluble CD40L (sCD40L), we sought to determine their involvement in CD40/CD40L-dependent immune responses and to understand the interactions between platelets and peripheral B lymphocytes. Materials and Methods. We examined the capacity of platelets to bind nonstimulated B cells, and phenotypic changes by flow cytometry and confocal scanning laser microscopy. Modulation of cytokines/chemokines and total levels of immunoglobulin (Ig) A, IgG, IgM, and IgG subclasses in supernatants of coculture, platelets, and B lymphocytes was performed by sandwich enzyme-linked immunosorbent assay and differential production of cytokine mRNA as determined by reverse transcriptase polymerase chain reaction. Results. In coculture, platelets and B lymphocytes were mutually activated, as demonstrated by the increased expression of platelet CD62p and B-cell CD86. Platelet/B-cell interactions were accompanied by changes in membrane expression of CD40 and CD40L by both platelets and B lymphocytes. IL12p70 and IL8 gene transcription were significantly reduced, which was attributable to B cells. Conversely, there was a significant, platelet-dependent reduction of sCD40L and RANTES mRNA expression. After a 3-day incubation with platelets, differentiated B cells increased their in vitro production of IgG1, IgG2, and IgG3, but not IgG4, IgA, or IgM. Conclusion. These data emphasize the potentially important role of platelets in the adaptive immune response. Platelets have an immunoregulatory role that might be applied clinically in multitransfused patients (e.g., hematopoietic stem cell transplantation). Ó

- by Fabrice Cognasse and +1
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- Flow Cytometry, Experimental, B Lymphocytes, Immunoglobulins

Immunoglobulin new antigen receptors (IgNARs) are unique single domain antibodies found in the serum of sharks. The individual variable (VNAR) domains bind antigen independently and are candidates for the smallest antibody-based immune recognition units (approximately 13 kDa). Here, we first isolated and sequenced the cDNA of a mature IgNAR antibody from the spotted wobbegong shark (Orectolobus maculatus) and confirmed the independent nature of the VNAR domains by dynamic light scattering. Second, we asked which of the reported antibody fragment dimerisation strategies could be applied to VNAR domains to produce small bivalent proteins with high functional affinity (avidity). In contrast to single chain Fv (scFv) fragments, separate IgNARs could not be linked into a tandem single chain format, with the resulting proteins exhibited only monovalent binding due solely to interaction of the N-terminal domain with antigen. Similarly, incorporation of C-terminal helix-turn-helix (dhlx) motifs, while resulting in efficiently dimerised protein, resulted in only a modest enhancement of affinity, probably due to an insufficiently long hinge region linking the antibody to the dhlx motif. Finally, generation of mutants containing half-cystine residues at the VNAR C-terminus produced dimeric recombinant proteins exhibiting high functional affinity for the target antigens, but at the cost of 50-fold decreased protein expression levels. This study demonstrates the potential for construction of bivalent or bispecific IgNAR-based binding reagents of relatively small size (approximately 26 kDa), equivalent to a monovalent antibody Fv fragment, for formulation into future diagnostic and therapeutic formats.

- by David Simmons
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- Immunology, Sharks, Dynamic Light Scattering, Solubility

Shell-on eggs cooked by immersion in water at low and constant temperatures (∼60-70°C) yield yolks with very particular textures. Structure development in such unique cooking conditions is far from understood. The present study shows that egg yolk, despite its compositional complexity, follows typical gelation kinetics found in many globular proteins and that it can develop structure at temperatures as low as 56°C. It follows that yolk texture is dictated by time/ temperature combinations. Under isothermal, low temperature cooking conditions, the thickening and gelation kinetics of egg yolk follow Arrhenius-type kinetic relationships. The energy of activation of these processes was ∼470 kJ mol −1 , which agrees well with the values reported for the denaturation and gelation of the thermally labile chicken serum albumin and immunoglobulin Y. Results are related to common foodstuffs in order to allow chefs and home cooks to achieve a priori conceived textures in egg yolks.

- by Cesar Vega
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- Gastronomy, Kinetics, Texture, Low Temperature

The Ig-genes of the heavy chains in anti-D-specific hybridomas and Fab/scFv-fragments selected from phage-display libraries are restricted to a group of closely related genes (IGHV3s genes). We analyzed the Ig-gene repertoire in anti-D-specific B cells of two hyperimmunized donors using a completely different method. Single B cells were cultured for 10 days in an EL4.B5 culture system. mRNA from anti-D-producing B cells was reverse transcribed into cDNA. Heavy-and light-chain gene rearrangements were amplified by PCR reactions, sequenced and cloned into a pNUT-vector system, thereby allowing the production of complete IgG and IgM. Eleven anti-D-specific B-cell clones were isolated and analyzed. Eight of these clones (including IgM-producing clones) had IGHV3s genes. We demonstrated that functional anti-D-specific IgM (4 clones) and IgG (2 clones) was produced. Using a new method, we analyzed the IGHV gene repertoire of anti-D-specific B cells of hyperimmunized donors and showed that it is indeed restricted. Moreover, we found a high frequency (1:100 and 1:500) of anti-D-specific B cells in the peripheral B cells of hyperimmunized donors. We suggest that this approach could be applied for the selection of human mAbs from immunized donors and for the analysis of Ig-gene repertoires at the single-B cell level.

- by Arend Mulder
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- Immunology, High Frequency, Phage display, PDL

C-protein is a major component of skeletal and cardiac muscle thick filaments. Mutations in the gene encoding cardiac C-protein [cardiac myosin binding protein-C (cMyBP-C)] are one of the principal causes of hypertrophic cardiomyopathy. cMyBP-C is a string of globular domains including eight immunoglobulin-like and three fibronectin-like domains termed C0-C10. It binds to myosin and titin, and probably to actin, and may have both a structural and a regulatory role in muscle function. To help to understand the pathology of the known mutations, we have solved the structure of the immunoglobulin-like C1 domain of MyBP-C by X-ray crystallography to a resolution of 1.55 Å. Mutations associated with hypertrophic cardiomyopathy are clustered at one end towards the C-terminus, close to the important C1C2 linker, where they alter the structural integrity of this region and its interactions.

AbstractöThere is growing evidence to suggest that growth hormone plays a role in the growth and development of the CNS. Speci¢cally, growth hormone has been implicated in promoting brain growth, myelination, neuronal arborisation, glial di¡erentiation and cognitive function. Here we investigate if growth hormone has a role in the recovery from an unilateral hypoxic^ischaemic brain injury. Using moderate (15 min hypoxia) and severe (60 min hypoxia) models of hypoxic^ischaemia in juvenile rats and standard immunohistochemical techniques, we found intense growth hormone-like immunoreactivity present within regions of cell loss by 3 days (P 6 0.05). Growth hormone-like immunoreactivity was observed on injured neurones, myelinated axons, glial cells within and surrounding infarcted tissue and on the choroid plexus plus ependymal cells within the injured hemisphere. The pattern of immunoreactivity suggests that (a) growth hormone (or a growth hormone-like substance) is transported via the cerebrospinal £uid and (b) that growth hormone (or a growth hormone-like substance) is acting in a neurotrophic manner speci¢cally targeted to injured neurones and glia.

- by Arjan Scheepens
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- Neuroscience, Psychology, Immunohistochemistry, Apoptosis

Objectives Old age is associated with irregularities in many aspects of body immune system function. During
this period, the immune responses decline with increasing age. In other words, with decreasing number of immune
cells, which are responsible for detecting and direct attack to contaminated cells, the immune response
decreases and results in failure of the immune system. As sports activities could affect the immune system and
old age is associated with progressive immune failure, the study of the effects of exercise on the immune system
function in old age becomes important. Therefore, this study aimed to investigate the effects of selected
combined exercises (aerobic and resistance training) on the serum level of cortisol and immunoglobulins in
inactive elderly men.
Methods & Materials In this quasi-experimental study, 24 subjects were selected by convenience sampling
method. Their age and body mass index ranged 60–70 years and 22–25 kg/m2, respectively. Then, they were
randomly assigned into 2 groups (experimental [n=12] and control [n=12]). The experimental group started
the combined training exercise, and the control group continued their inactive usual routines. The combined
training exercise (aerobic-resistance) included running on a treadmill for 20 minutes per session, 3 sessions per
week, for 8 weeks, with an intensity of 60% to 70% HRR. Furthermore, the resistance training comprised 10
circling stationary movements of leg flexion, leg extension, leg press, scott, underarm stretch, chest press, iron
cross with dumbbells, biceps flexion, triceps extension, and rowing motion with rope. This training included an
intensity of 60% to 70% of one maximum repetition with extra load and 10 repetitions in 2 successive times
with 30 seconds rest between each repetition and 2 minutes’ rest between each movement. In this study, the
blood samples were taken 24 hours before the exercise and 24 hours after the last session of the exercise. We
used nephelometer instrument and binding kit site to measure the IgG, IgM, and IgA levels. The cortisol level
was measured by Gamacounter and RIA kit by the immunoradiometric method. To evaluate the consumed
oxygen, we used the protocol on treadmill instrument. In order to compare intra- and inter-group mean variables,
we used analyses of variance for repeated measures. The significant level was set at P<0.05.
Results The results indicated that the combined exercises reduced IgG level (12.75%) in the elderly people
(P=0.04). Although the level of serum IgM was also reduced (15.93%), this decrease was insignificant (P=0.31).
Furthermore, no significant change was seen in the IgA level (P=0.90). The cortisol level was significantly increased
(8.33%) in the experimental group (P=0.001). Based on the results, the mean intergroup changes
in the levels of IgA, IgA, and IgM were not significant (P>0.05). However, a significant difference was seen
between 2 groups with regard to serum cortisol level (P<0.05).
Conclusion Doing physical activities is one of the key factors in changing the function of the immune system.
This issue is associated with the intensity, duration, kind of exercise, body readiness, nutrition, mental status,
and hormonal factors. Based on the results, long and intensive exercises with an increase in the catabolic process
may weaken the immune system of the older people.

- by Salmand: Iranian Journal of Ageing and +1
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- Training, Elderly, Immunoglobulin

Safety and efficacy of imatinib in chronic eosinophilic leukaemia and hypereosinophilic syndrome-a phase-II study. FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 conscutive patients with moderate to severe... more
Safety and efficacy of imatinib in chronic eosinophilic leukaemia and hypereosinophilic syndrome-a phase-II study. FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 conscutive patients with moderate to severe eosinophilia. Blood, 104, 3038-3045.

- by John Shaughnessy
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- British, Multiple Myeloma, Survival Rate, Prognosis

The four human IgG isotypes are highly conserved in amino acid sequence, but show differential ability to activate complement (C'): IgG3 and IgGl are very active. IgG2 is active under certain conditions, and IgG4 is inactive. Although the second constant domain (C,2) is critical for C' activation, the individual amino acids that confer isotype-specific activity have not been identified. We have generated a series of mutants between IgG2 and IgG3, resulting in the exchange of the four N-terminal and six C-terminal polymorphic residues within C"2. Mutants containing the N-terminus of the C,2 of IgG3 were as effective as wildtype IgG3 in Clq binding, Cl activation and terminal complex (MAC) formation, but had reduced ability to effect C/-mediated lysis. IgG2 and mutants containing the N-terminal portion of the CH2 of IgG2 were reduced compared to IgG3 in activating Cl, binding Clq and inducing assembly of the MAC, and were inactive in mediating lysis of target cells. Thus, the amino acid sequence differences in the N-terminus of C,,2 play a critical role in determining the relative abilities of IgG2 and IgG3 to bind Clq and activate the C' cascade although additional residues of C,2 must be involved in mediating optimal target cells lysis. The sequence of the N-terminus of C,2 was less critical in determining C4 and C3 binding. Characterization of domain exchange mutants suggests that intermediate steps may be partly dependent on domains other than C,2. IgGs that do not direct target cell lysis nevertheless activate intermediate steps in the pathway, which may contribute to immune complex-associated disorders. pi;, 1997 Elsevier Science Ltd. All rights reserved.

- by Sherie L. Morrison
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- Immunology, Complement activation, DNS, Molecular Immunology

Turnouts with a plasmacytoid pattern taken from 32 dogs and finn" cats were examined for the presence Jimmunoglobulins, which would allow them to be designated as B-cell Iymphomas. Within a total ot" 19 immunogIobulinpositive turnouts, three types could be distinguished: extramedullary plasmacytoma (15), multiple myeloma (two) and immunocytoma (two). These tumours occurred in 18 of" the dogs, and in one cat (extramedullary plasmacytoma). The characteristics o[" the immunoglobulin-producing tumours were investigated by light and electron-mlcroscopy as well as by immunohistochemical rnethods. Seventeen of the l g tumom's expressed ~.-type light chains and one turnout K-type light chains. Heavy chains were also synthesized by five tuinoul's.

- by Stefan Platz
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- Electron Microscopy, Immunohistochemistry, Comparative, Cats

What are the selective pressures on protein sequences during evolution? Amino acid residues may be highly conserved for functional or structural (stability) reasons. Theoretical studies have proposed that residues involved in the folding nucleus may also be highly conserved. To test this we are using an experimental``fold approach'' to the study of protein folding. This compares the folding and stability of a number of proteins that share the same fold, but have no common amino acid sequence or biological activity. The fold selected for this study is the immunoglobulin-like b-sandwich fold, which is a fold that has no speci®cally conserved function. Four model proteins are used from two distinct superfamilies that share the immunoglobulin-like fold, the ®bronectin type III and immunoglobulin superfamilies. Here, the fold approach and protein engineering are used to question the role of a highly conserved tyrosine in the``tyrosine corner'' motif that is found ubiquitously and exclusively in Greek key proteins. In the four model b-sandwich proteins characterised here, the tyrosine is the only residue that is absolutely conserved at equivalent sites. By mutating this position to phenylalanine, we show that the tyrosine hydroxyl is not required to nucleate folding in the immunoglobulin superfamily, whereas it is involved to some extent in early structure formation in the ®bronectin type III superfamily. The tyrosine corner is important for stability, mutation to phenylalanine costs between 1.5 and 3 kcal mol À1 . We propose that the high level of conservation of the tyrosine is related to the structural restraints of the loop connecting the b-sheets, representing an evolutionary``cul-de-sac''.

- by stefan hamill
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- Molecular Biology, Protein Folding, Molecular Evolution, Evolution

Treatment of mice with hydroxyurea to selectively kill all cycling cells has been used to study population dynamics and life expectancy of “natural” immunoglobulin-secreting cells in the bone marrow and spleen of nonimmunized animals. The results show that 50 to 90% of those cells are eliminated 2 to 3 days after one cycle of hydroxyurea administration, demonstrating their recent origin from cycling precursors. Using a protocol of long-term hydroxyurea treatment which abrogates cell production from the cycling precursors compartments, it was shown that “natural” immunoglobulin-secreting cells have a very short half renewal time, in the range of 15–60 h.

- by António Freitas
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- Immunology, Stem Cells, Aging, Cell Cycle

The large surface area, good vascularization, immense capacity for solute exchange and ultra-thinness of the alveolar epithelium are unique features of the lung that can facilitate systemic delivery via pulmonary administration of peptides and proteins. Physical and biochemical barriers, lack of optimal dosage forms and delivery devices limit the systemic delivery of biotherapeutic agents by inhalation. Current efforts to overcome these difficulties in order to deliver metabolic hormones (insulin, calcitonin, thyroid-stimulating hormone [TSH], follicle-stimulating hormone [FSH] and growth hormones) systemically, to induce systemic responses (immunoglobulins, cyclosporin A [CsA], recombinant-methionyl human granulocyte colony-stimulating factor [r-huG-CSF], pancreatic islet autoantigen) and to modulate other biological processes via the lung are reviewed. Safety aspects of pulmonary peptide and protein administration are also discussed.

- by renaat kinget
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- Growth Hormone, Insulin, Peptides, Drug Delivery Systems

Haemophilus somnus is an important cause of bovine respiratory disease and septicemia with all it's sequelae. The role of immune responses in protection and immunopathogenesis is not well understood. We showed that infection with bovine respiratory syncytial virus (BRSV) 6 days before H. somnus increased clinical scores and levels of IgE antibody to H. somnus over that of infection with H. somnus alone. To determine whether antigenic specificity of IgE responses differed from IgG responses, Western blots were done with sera from the infected calves, at 0 time and at 21 days post infection. Thus each calf was its own control. IgG antibodies recognized primarily a 40 kDa outer membrane protein (OMP) in whole cell H. somnus preparations and a 270 kDa immunoglobulin binding protein (IgBPs) in culture supernatants but generally not the 41 kDa major OMP (MOMP). IgE antibodies recognized primarily the 41 kDa MOMP in whole cell pellet preparations. Results were consistent among calves. With culture supernatants, IgE antibodies recognized both the 270 kDa IgBPs and the MOMP. Since some H. somnus strains from asymptomatic carriers (including strain 129Pt), do not have IgBPs and express a truncated MOMP (33 kDa rather than 41 kDa), reaction of strain 129Pt cells with serum from calves infected with H. somnus or BRSV and H. somnus was studied. IgE did not react with the truncated MOMP even at much lower (1:100) dilutions than in Western blots with virulent strain 2336 (serum dilution of 1:500). Reactions of IgE with the 40 and 78 kDa antigens in strain 129Pt were noted but since the major reactivities with the IgBPs and the MOMP were not detected, this strain may be useful for inducing protective rather than immunopathogenic responses. #

- by Richard Kimball
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- Zoology, Immune response, Western blotting, Immunoglobulin E

The current study aimed to evaluate the influence of domestication process on the stress response and subsequent immune modulation in Eurasian perch juveniles (Perca fluviatilis) submitted to chronic confinement. Briefly, F1 and F4 generations were confined into small-size tanks and sampled 7 and 55 days after stocking. Cortisol and glucose levels as well as lysozyme activity and immunoglobulin level were evaluated in the serum. Spleen Somatic Index and spleen ROS production were also measured. A proteomic analysis was performed on serum sampled on day 7. Finally, both generations were genetically characterized using a microsatellite approach. Globally, results revealed that chronic confinement did not elicit a typical stress response but resulted in a prolonged immune stimulation. Proteomic results suggested that domestication process influenced the immune status of perch submitted to chronic confinement as the F1 confined fish displayed lower abundance of C3 complement component, transferrin and Apolipoprotein E. Microsatellite data showed a strong genetic drift as well as reduced genetic diversity, allelic number and heterozygosity along with domestication process. The present work is the first to report that fish under domestication can develop an immune response, assessed by a combined approach, following recurrent challenges imposed by captive environment despite a reduced genetic variation.

- by Martine Raes and +1
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- Genetics, Zoology, Immune response, Genetic Drift

Natural killer (NK) cells express receptors that are specific for MHC class I molecules. These receptors play a crucial role in regulating the lytic and cytokine expression capabilities of NK cells. In humans, three distinct families of genes have been defined that encode for receptors of HLA class I molecules. The first family identified consists of type I transmembrane molecules belonging to the immunoglobulin (Ig) superfamily and are called killer cell Ig-like receptors (KIR). A second group of receptors belonging to the Ig superfamily, named ILT (for immunoglobulin like transcripts), has more recently been described. ILTs are expressed mainly on B, T and myeloid cells, but some members of this group are also expressed on NK cells. They are also referred to as LIRs (for leukocyte Ig-like receptor) and MIRs (for macrophage Ig-like receptor). The ligands for the KIR and some of the ILT receptors include classical (class Ia) HLA class I molecules, as well as the nonclassical (class Ib) HLA-G molecule. The third family of HLA class I receptors are C-type lectin family members and are composed of heterodimers of CD94 covalently associated with a member of the NKG2 family of molecules. The ligand for most members is the nonclassical class I molecule HLA-E. NKG2D, a member of the NKG2 family, is expressed as a homodimer, along with the adaptor molecule DAP10. The ligands of NKG2D include the human class I like molecules MICA and MICB, and the recently described ULBPs. Each of these three families of receptors has individual members that can recognize identical or similar ligands yet signal for activation or inhibition of cellular functions. This dichotomy correlates with particular structural features present in the transmembrane and intracytoplasmic portions of these molecules.

- by Rafael Solana
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- Genetics, Immunology, Signal Transduction, Protein Structure and Function
- by Laszlo Hosszu and +2
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- Protein Folding, Kinetics, Mice, Hydrogen Bonding

In the early 1970s an increased prevalence of gallstones was reported in adults and children with immunoglobulin deficiency. As the advent of ultrasonography has largely changed the diagnostic approach to gallstones, we have reevaluated the prevalence of cholelithiasis in a group including 37 patients with common variable immunodeficiency and seven patients with other forms of primary immunodeficiency. All patients were receiving intravenous gammaglobulin replacement since 1983 or, in more recent cases, soon after the diagnosis was made, and therefore had relatively few infections. All patients underwent a hepatobiliary ultrasonogram and blood sampling. Data were compared, after age and sex standardization, with those obtained by the GREPCO in a free-living population of 1239 men and 1081 women. Only two women with immunoglobulin deficiency had gallstones. One of these was obese and had had one pregnancy. Both were asymptomatic. None of the patients studied had a history of cholecystectomy or evidence of biliary sludge. Thus, the observed prevalence rates of gallstone disease were 8.7% in women and 0% in males, respectively, against expected values of 9.5% and 3.2%. Immunodeficient patients expressed several putative risk factors for gallstones in the low range (body mass index, total and HDL cholesterol, and blood glucose in both sexes, and triglycerides in men). We conclude that gallstone disease is not more frequent in patients with immunodeficiency syndromes undergoing immunoglobulin therapy than in the general population.

- by Adriano Santis
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- Blood Glucose, Primary Immunodeficiency, Ultrasonography, Blood sampling

In this study, we quantified the adsorption of immunoglobulin G (IgG) protein onto several polyelectrolyte-modified sintered porous polyethylene (PPE) membranes. The polymer surfaces had both cationic and anionic charges obtained via the adsorption of polyethylenimine (PEI) and polyacrylic acid (PAA), respectively, onto plasma-activated PPE. The amount of IgG adsorption was determined by measuring the gamma radiation emitted by [ 125 I]-IgG radio labeled protein. By studying the impact of pH and ionic strength on IgG adsorption, we attempted to characterize the role and nature of the electrostatic interactions involved in the adsorption process to better understand how these interactions were influenced by the charge and structure of immobilized polyelectrolyte complexes at modified membrane surfaces. We were able to show that surface modification of PPE membranes with adsorbed PEI monolayers and PEI-PAA bilayers can greatly improve the IgG binding ability of the membrane under optimized conditions. We also showed that the observed improvement in the IgG binding is derived from electrostatic interactions between IgG and the polyelectrolyte surface. In addition, we found that the greatest IgG adsorption occurred when the IgG and the surface possessed predominantly opposite charges, rather than when the surface possessed the greatest electrostatic charge. Finally, we have found that the molecular weight of the terminating polyelectrolyte has a noticeable effect upon the electrostatic interactions between IgG and the PEI-PAA bilayer-modified PPE surfaces. r

- by Rina Tannenbaum
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- Biomaterials, Protein adsorption, Polyelectrolytes, Polymers
- by Rudolf Grosschedl
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- Immunology, Transcription Factors, Cell Differentiation, Transcription Factor

A comparative approach is potentially useful for understanding the role of mammal innate immunity role in stimulating adaptive immunity as well as the relationship between these two types of immune strategies. Considerable progress has been made in the elucidation of the co-ordinated events involved in plant perception of infection and their mobilisation of defence responses. Although lacking immunoglobulin molecules, circulating cells, and phagocytic processes, plants successfully use pre-formed physical and chemical innate defences, as well as inducible adaptive immune strategies. In the present paper, we review some shared and divergent immune aspects present in both animals and plants. ᮊ

- by Carlos Jared
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- Innate immunity, Signal Transduction, Biological Sciences, Environmental Sciences

Infection by the liver fluke (Opisthorchis viverrini) causes hepatobiliary disease and bile duct cancer (cholangiocarcinoma, CCA) in endemic areas in Southeast Asia. Measurements of humoral immune response particularly parasite-specific antibodies are useful not only for serodiagnosis but they have been implicated as risk factors of CCA. In this study, we used indirect Enzyme Immunosorbent Assay (ELISA) to measure O. viverrini-specific immunoglobulins in serum, urine and saliva and assessed efficacies in diagnosis of opisthorchiasis and evaluated the relationship of antibodies among clinical specimens in a sample population in endemic areas in Khon Kaen, Thailand. By employing the Receiver Operation Characteristics (ROC) analysis, diagnostic efficacy based upon the area under the curve (AUC) revealed that serum, salivary IgG and IgA performed better than urine for diagnosis of opisthorchiasis. Seropositive cases were found in both parasite egg-negative as well as O. viverrini egg-positive groups. The levels of serum IgG correlated with intensity of O. viverrini infection (P b 0.05). Diagnostic sensitivities based on serum and salivary IgG, IgA also positively associated with the intensity of infection. Correlations between serum antibodies and those in saliva were found to be greater in egg-negative than egg-positive individuals for O. viverrini. Our findings indicated a complex interrelation between antibody responses in different clinical specimens triggered by liver fluke infection. More comprehensive examinations are needed to determine the potential utility of salivary antibody detection which, in combination with the conventional fecal examination method, may better assist in the identification of individuals with opisthorchiasis. Furthermore, it may provide a better indicator of the risk of disease, particularly CCA.

- by Eimorn Mairiang
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- Microbiology, Parasitology, Southeast Asia, Medical Microbiology

The total number of spontaneously occurring ("background") IgM-, IgG-, and &A-secreting cells and the frequency of antigen-specific IgM-, IgG-, and IgA-secreting cells were determined in germ-free BALB/c mice fed a chemically defined ultrafiltered diet (GF-CD), in specific pathogen-free BALB/c mice fed an autoclaved natural ingredient diet (SPF-NI), and in conventional BALB/c mice fed nonautoclaved natural ingredients (CV-NI). This was done by means of the ELISA-plaque assay. The results did not show differences among the various groups of mice with regard to the total numbers of &@-secreting cells in the various lymphoid organs. Also the frequencies of IgM-secreting cells specific for DNP27-BSA and the anti-idiotypic monoclonal antibodies Ac38 and Acl46 did not differ significantly among GF-CD, SPF-NI, and CV-NI mice. GF-CD mice, however, did show substantially decreased numbers of IgG-and IgA-secreting cells in their lymphoid organs. Furthermore, there were striking differences in the frequencies of antigen-specific IgG-and IgA-secreting cells between GF-CD mice and the two other groups of mice. These results indicate that exogenous antigenic stimulation has a great effect on both the total numbers and the specificity repertoires of background IgG-and IgA-secreting cells. Such an influence could not be detected with regard to the background IgM-secreting cells. This suggests two distinct compartments of background Ig-secreting cells: a very stable, endogenously regulated compartment consisting mainly of IgM-secreting cells, and another compartment, consisting mainly of IgG-and &A-secreting cells, whose numbers and specificity repertoire appeared to be influenced by exogenous antigenic stimulation. Q 1988 Academic press, IX.

- by Cornelia van Helden-Meeuwsen and +1
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- Immunology, Cellular Immunology, Mice, Bovine Serum Albumin

Surface associated pneumococcal proteins ␣-enolase (Eno), immunoglobulin A1 protease (Iga), streptococcal lipoprotein rotamase A (SlrA), and putative proteinase maturation protein A (PpmA) have potential as candidates for future protein-based anti-pneumococcal vaccines. The immunogenicity of these proteins were studied in a cohort of 329 children during their first two years of life. During the first recorded episode of otitis media, acute and convalescent phase sera were available from 151 children. Concentrations of antibodies against Eno, Iga, SlrA and PpmA were measured by EIA and detected in 99% (300/302), 95% (288/302), 95% (288/302), and 83% (251/302) of the sera, respectively. There were no statistically significant differences between the groups of children with and without a history of pneumococcal contact or with respect to the type of pneumococcal contact. Despite a mean overall decrease in the antibody titers in the convalescent sera following AOM, several children were able to respond with a more than twofold increase in antibody titer in response to AOM. The majority of the children with increased antibody concentrations appeared in the groups, which were colonized with pneumococci at the time of serum collection, but were recorded as having no prior contact with pneumococci. In conclusion, SlrA, PpmA, Eno and Iga are immunogenic proteins that elicit antibody responses early in life. No significant correlation between antibody titers to these proteins and pneumococcal carriage or infection was found. Presumably, this results from the presence of cross-reactive epitopes on commensal bacteria.

- by Peter Adrian
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- Streptococcus pneumoniae, Biological Sciences, Statistical Significance, Infant

Background: Pemphigus is a rare life-threatening intractable autoimmune blistering disease caused by IgG autoantibodies to desmogleins. It has been difficult to conduct a double-blind clinical study for pemphigus partly because, in a... more

- by Fumio Kaneko and +4
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- Dermatology, Clinical Sciences, Time Factors, Immunoglobulins

Serum samples and immunoglobulin fraciions of eight mammalian species were applied to a Sepharose-protein A column. As with the human immunoglobulin subclasses IgGl, lgG2 and IgG4, all examined animal IgG classes and subclasses were bound to a greater or lesser extent lo protein A. However, the binding of IgGl of ruminants was very poor. Polyclonal IgM and IgA of the pig, the dog and the cat may be separated in protein A reactive and protein A non-reaciive fractions. In addition, monoclonal canine IgM and IgA partially reacted with protein A. In combination with methods such as ammonium sulphate precipitation, ion exchange chromatography and gel-filtration, affinity chromatography with protein A is recommended for the rapid purification of certain Ig (sub)classes of a number of mammalian species.

- by A. Noordzij
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- Immunology, Cats, Dogs, Sheep

Immunoglobulins have initially been illustrated as proteins produced by the immune system for binding and neutralizing foreign molecules potentially harmful to the organism. The number of V H , D H , J H , V L and J L genes that encode the variable regions of immunoglobulins and the junctional diversity that occurs at the time of somatic rearrangement determine the extent of the repertoire of antibodies that may be potentially produced by an organism. This potential repertoire includes antibodies the antigen binding site of which may recognize external as well as autologous antigens, or may structurally resemble the active site of enzymes and be endowed with enzymatic activity. Under physiological conditions, B cell clones that produce antibodies naturally endowed with catalytic activity are negatively regulated and subjected to apoptosis. Catalytic antibodies are expressed only following active immunization, or if the physiological regulatory mechanisms that control the expression of catalytic antibody-producing B cell clones are perturbed, e.g. in the context of pregnancy or in the course of autoimmune diseases.

- by Srinivas KAVERI
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- Immunology, Autoimmune Disease, Autoimmune diseases, Immunization

Topical therapies are the mainstay in the treatment of atopic dermatitis, and are effective in the majority of patients with mild and localized disease. In patients with widespread or recalcitrant moderate to severe dermatitis, systemic therapies may be required. The frequently used systemic therapies are immunosuppressants, immune response modifiers, antiinflammatories, antihistamines, and antibiotics. In this article, the indications and scientific support for the use of these medications is reviewed. Table 7 A proposed algorithm for the systemic treatment of paediatric atopic dermatitis Atopic dermatitis Discoid dermatitis First line: cyclosporin Second line: azathioprine Third line: methotrexate Fourth line: mycophenolate mofetil, intravenous immunoglobulin, interferon-g First line: methotrexate Second line: cyclosporin 132 KLA Borchard and D Orchard

Progress in the treatment of inflammatory myopathies is impeded by the lack of suitable animal models. Inflammatory myopathies occur spontaneously in the dog, are a heterogeneous group of disorders, and are more common than in humans. Clinical signs of weakness and muscle atrophy are reliably present, and there are histological and immunohistological similarities to forms of human myositis. In this study, microarray technology followed by quantitative real-time PCR and immunohistochemistry on muscle biopsy sections was used to investigate gene expression in cases of canine inflammatory myopathies. Several genes involved with innate and adaptive immunity were highly upregulated including those that participate in macrophage and dendritic cell activation and migration, and antigen processing and presentation. Other genes including those that participate in B cell growth, development, migration and activation, immunoglobulin genes, genes in pro-inflammatory and anti-inflammatory pathways, and genes involved with tissue remodeling were upregulated. In previous reports utilizing microarray technology in human myositis, there was activation of similar pathways involved in the immune response. This study strengthens the argument that forms of canine myositis may be important animal models of human myositis and suggests useful biomarkers for therapeutic response using the dog in pre-clinical trials. #

- by Svetlana Ghimbovschi
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- Zoology, Immune response, Skeletal muscle biology, Clinical Trial

Abstracts / La Revue de médecine interne 31S (2010) S342-S403 S363 immuno-modulateurs de la famille des IMiDS et le bortézomib dans la survie globale, nous avons conduit une étude rétrospective mono-centrique incluant les patients suivis pour un myélome multiple dans un service de médecine interne depuis dix ans. Patients et méthodes.-Nous avons colligé toutes les localisations extra-médullaires et extra-osseuses survenues chez les patients suivis pour myélome multiple dans le service de médecine interne du CHU d'Amiens de janvier 2000 à septembre 2010. Nous avons étudié les caractéristiques démographiques, biologiques, cytogénétiques, le délai d'apparition par rapport à la date de diagnostic, les traitements reç us lors de la prise en charge du myélome multiple et en particulier de ces formes extra-médullaires et extra-osseuses, la réponse aux traitements et la survie globale. Résultats.-Nous avons inclus 142 patients parmi lesquels seuls six [H/F = 4/2, âge moyen au diagnostic : 60 ans (46-69)] ont présenté des formes extra-médullaires et extra-osseuses avec des localisations diverses : peau et tissus mous (n = 3)

- by JD J D de Korwin
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- Immunoglobulin
- by Jana Kayserova and +2
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- Immunology, Infant, Immunoglobulin E, Biological markers

Background: Ocular cicatricial pemphigoid is a chronic, progressive, autoimmune disease that scars mucous membranes and may lead to blindness. It is of critical importance to be able to make the diagnosis as early as possible to allow... more

- by Anthony Rodriguez
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- Ophthalmology, Conjunctiva, Biopsy, Autoimmune Disease

Malignancies arising from biliary tract epithelia, or cholangiocarcinoma, are rare tumors that have a poor prognosis. The incidence of these tumors is gradually increasing in many countries. Recent advances have been made in identifying some of the risk factors, and the need for appropriate classification is emerging. The diagnosis of cholangiocarcinoma is often difficult and requires multiple complementary studies. The use of molecular approaches may improve the diagnostic utility of biliary cytology. Treatment of these tumors is complex, and there are many different treatment options. Although surgical resection can be curative, many patients with cholangiocarcinoma are diagnosed at an advanced stage when only palliative approaches can be used. Photodynamic therapy is emerging as a useful modality.

- by santosh reddy
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- Epidemiology, Gastroenterology, Palliative Care, Life Style

Aviscumine is an Escherichia coli-derived recombinant type II ribosome-inactivating protein with potent antitumor activity in vitro and in vivo. It is the recombinant counterpart of natural mistletoe lectin-I. The current study was performed to determine the safety profile, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of the intravenous (i.v.) administration of aviscumine in cancer patients. Translational research included the evaluation of pharmacokinetics and monitoring of plasma cytokine and anti-aviscumine antibody induction after administration of the drug. Aviscumine was given twice weekly as a 1 h central i.v. infusion in patients with advanced, refractory progressive, solid malignant tumors who had not been previously exposed to natural mistletoe preparations. They had histologically or cytologically verified disease, were > or =18 years old, had an Eastern Cooperative Oncology Group performance status < or =2 and adequate bone marrow, liver and renal ...

- by S. Marreaud
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- Clinical Trial, Breast Cancer, Treatment Outcome, Drug development

Axonin-I is an axon-associated cell adhesion molecule (AxCAM) of the chicken, which promotes neurite outgrowth by interaction with the AxCAM Ll(G4) of the neuritic membrane. Here we report the cloning and sequence determination of a cDNA encoding axonin-I, Peptides generated by enzymatic cleavage showed similarity to the AxCAM F11. Degenerated polymerase chain reaction (PCR) primers were designed and an axonin-I fragment was amplified from mRNA of embryonic retina. Screening of a cDNA library from embryonic brain resulted in the isolation of a 4.0-kb cDNA insert with an open reading frame of 3108 nucleotides. The deduced polypeptide of 1036 amino acids includes a putative hydrophobic N-terminal signal sequence of 23 or 25 amino acids and a C-terminal hydrophobic sequence of 29 amino acids which is suggestive of sequences serving as signal for the attachment of a glycosyl-phosphatidylinositol (glycosyl-PtdIns) anchor. The putative mature form of axonin-1 comprises six immunoglobulin-like repeats, followed by four fibronectin-type I11 repeats.

- by Esther Stoeckli and +1
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- DNA, Brain, Sequence alignment, Polymerase Chain Reaction

The aim of the research was to evaluate the effects of immunoglobulin G (IgG) colostrum concentration on goat kid immune status when the total amount of IgG fed was constant. Majorera goat kids (n = 56) were randomly assigned to 1 of 4 groups, and kids received 4 g of IgG per kg of body weight of atomized colostrum at 4 different IgG concentrations: 20 (AC-20), 40 (AC-40), 60 (AC-60), and 80 (AC-80) mg/mL. Blood samples were obtained on d 0, 1, 2, 3, 4, and 5 postpartum. Immunoglobulin G, IgA, and IgM plasma concentrations, apparent efficiency of absorption of IgG, plasma chitotriosidase activity, plasma complement activity, and plasma proteinogram were measured. Plasma IgG and IgM concentrations were highest on d 1 in AC-80 animals, and IgA plasma concentration was lower in AC-20 than in AC-80. The apparent efficiency of absorption was higher in AC-80 (24.4%) than in the other treatment groups (by an average of 13.8%). Chitotriosidase plasma activity on d 5 (1,488 nmol/mL per hour) was higher than on d 0 and 1 (average of 1,183 nmol/mL per hour). There were no effects of colostrum IgG concentration on complement activity and plasma protein distribution, but γ-globulin and α-globulin were lower on d 0 than on d 1, 2, 3, 4, and 5. Increasing the immunoglobulin concentration in colostrum using atomized colostrum improves the immunoglobulin absorption at the same amount of immunoglobulin fed.

- by Anastasio Arguello
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- Complement activation, Dairy Science, Animal Production, Blood sampling
- by Zhiyuan Gong
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- Immunology, T cell receptor, Danio rerio, Western blotting

We report eight novel members of the superfamily of human G protein-coupled receptors (GPCRs) found by searches in the human genome databases, termed GPR97, GPR110, GPR111, GPR112, GPR113, GPR114, GPR115 and GPR116. Phylogenetic analysis shows that these are additional members of a family of GPCRs with long N-termini, previously termed EGF-7TM, LNB-7TM, B2 or LN-7TM. Five of the receptors form their own phylogenetic cluster, while three others form a cluster with the previously reported HE6 and GPR56 (TM7XN1). All the receptors have a GPS domain in their N-terminus and long Ser/Thr-rich regions forming mucin-like stalks. GPR113 has a hormone binding domain and one EGF domain. GPR112 has over 20 Ser/Thr repeats and a pentraxin domain. GPR116 has two immunoglobulin-like repeats and a SEA box. We found several human EST sequences for most of the receptors showing di¡erential expression patterns, which may indicate that some of these receptors participate in reproductive functions while others are more likely to have a role in the immune system.

- by Pär Höglund
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- Reproduction, Adhesion, Phylogeny, Phylogenetic analysis

Urbanization generates human-made habitats with novel resources. Such change is not homegeneous, and includes different urban land uses characterized by specific habitat traits. In this study we explored the ecophysiologial response of an urban-exploiter species in three different urban land uses (urban, suburban, industrial). Our results show that corticosterone (obtained through fecal samples) and immunoglobulin (obtained through blood samples) concentrations did not differ significantly among the studied urban land uses. Corticosterone and immunoglobulin concentration showed both high and low values in urban and suburban areas, while industrial areas had low and high levels of corticosterone, and medium-to-low immunoglobulin concentration values. Also, we found a negative relationship between corticosterone and immunoglobulin concentrations in industrial areas. Based on corticosterone and immunoglobulin concentration thresholds established from previous studies, our results suggest that:

- by Jorge Schondube
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- Engineering, Stress, Ecology, Urban Ecology
- by nathalia costa
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- Case Report, Platelet aggregation, Autosomal Recessive, Bleeding Time

FTIR spectroscopic and texture analysis studies were undertaken to elucidate the molecular basis of structure-functionality relationships of porcine plasma proteins in solution and the gel state at varying pH. At room temperature, porcine plasma proteins aggregated as a function of decreasing pH. A parallel decrease in the intensity of amide I 0 bands at 1652 cm À1 in the infrared spectra of the protein solution (assigned to a-helix, predominant in serum albumin) and 1688/1638 cm À1 (assigned to intramolecular antiparallel b-sheet, predominant in immunoglobulins) along with an increase in the band at 1644 cm À1 (assigned to unordered or random structure) was observed to take place with decreasing pH. Bands assigned to intermolecular antiparallel b-sheet structures (1683 and 1617 cm À1 ) were observed in infrared spectra of porcine plasma protein solutions heated to the point of gel formation. Texture and water holding capacity were also very sensitive to pH. The results indicate that the lower the remaining native secondary structure and the faster the heat-induced aggregation (observed by FTIR spectroscopy) with decreasing pH, the weaker and more exudative the gels. r

- by Elena Saguer
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- FTIR spectroscopy, Texture Analysis, Secondary Structure, Room Temperature

Natural Killer (NK) cells may be involved both in allogeneic bone marrow transplantation (BMT) rejection and graft-versus-host disease (GVHD). The physiologic functions of NK cells appear to be regulated by diverse non-inhibitory and inhibitory receptors including the killer cell immunoglobulin-like receptors (KIR). Although human leukocyte antigen (HLA) epitope mismatches are well-known causes of NK alloreactivity, the role of KIR genes in transplantation remains to be further investigated. In this study, we have evaluated whether KIR genotype differences between donors and recipients of HLA identical (related and unrelated) compared with HLA non-identical unrelated BMT, had an impact on transplantation outcome. Our results show that 5 of 15 KIR genes were always identical in donors and recipients and most variations were observed in the number and specificity of noninhibitory KIR genes. Based on the presence or absence of particular KIR genes, 70 different genotypes were obtained from all individuals. According to the donor or recipient KIR genotype, different combination patterns were described. Interestingly, when the recipient KIR genotype was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;included&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; in the donor KIR genotype, 100% (11/11 pairs) of unrelated BMT developed GVHD compared with 60% (18/30) in all other combinations (p = 0.012). In contrast, no GVHD was observed in related BMT when the recipient KIR genotype was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;included&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; in the donor KIR genotype (p = 0.0001). In conclusion, our results reveal a great diversity for KIR genotypes in donors and recipients of BMT and that the risk of GVHD was maximum in unrelated BMT when the recipient KIR genotype was &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;included&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; in the donor KIR genotype.

- by Anne Cesbron and +2
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- Immunology, Treatment Outcome, Adolescent, Child