Jerry Winkelstein - Academia.edu (original) (raw)
Papers by Jerry Winkelstein
Journal of Immunology, Jul 1, 1978
Journal of Clinical Investigation, Dec 15, 1998
Chronic granulomatous disease (CGD) is an inherited disorder of phagocyte function in which defec... more Chronic granulomatous disease (CGD) is an inherited disorder of phagocyte function in which defective superoxide production results in deficient microbicidal activity. CGD patients suffer from recurrent, life-threatening infections, and nearly half develop chronic gastrointestinal (GI) complications (colitis, gastric outlet obstruction, or perirectal abscess) and/or autoimmune/rheumatologic disorders (AIDs). To identify genetic modifiers of disease severity, we studied a cohort of 129 CGD patients, in whom seven candidate genes (myeloperoxidase [MPO], mannose binding lectin [MBL], Fc ␥ receptors IIa, IIIa, IIIb, TNF-␣ , and IL-1 receptor antagonist), each containing a physiologically relevant polymorphism predicted to influence the host inflammatory response, were selected for analysis. Genotypes of MPO (P ϭ 0.003) and Fc ␥ RIIIb (P ϭ 0.007) were strongly associated with an increased risk for GI complications, while an Fc ␥ RIIa (P ϭ 0.05) genotype was suggestive for an association. Patients with all three associated genotypes had the highest risk for GI complications (P Ͻ 0.0001). The risk of AIDs was strongly associated with variant alleles of MBL (P ϭ 0.01) and weakly associated with an Fc ␥ RIIa genotype (P ϭ 0.04). Patients with variant forms of both MBL and Fc ␥ RIIa had the highest risk of developing an AID (P ϭ 0.003).
Pediatric Research, Apr 1, 1977
A 44 nonth old Llack female with ornohalitis at 4 davs of aoe.- .
Pediatric Research, Apr 1, 1984
We have given marrow (BM)ablative doses of PAM followed by BM autografting to children with neuro... more We have given marrow (BM)ablative doses of PAM followed by BM autografting to children with neuroblastoma (NBL), Ewing's sarcoma (ES) and osteosarcoma (0s). To examine in vitro effects of this drug, we exposed fresh and cultured NBL (6 ES (41, OS (5) and normal BM (9) cell colonies (CFU) to PAM in concentrations (conc) from 10-I to lo-' molar in a 14 day clonigenic assay. The TI2 of PAM measured by high pressure liquid chromatography was about 45 minutes. All CFU showed linear responses to PAM, correlating with both increasing drug conc and exposure duration (up to 8 hours). Fresh cells were significantly more sensitive than cultured cells. NBL-CFU were most sensitive, followed by OS, BM and ES in decreasing order. Repeat dosing up to 4 doses of PAM further inhibited CFU formation. We conclude: (1) NBL and OS CFU are more sensitive to PAM than normal BM or ES CFU; (2) PAM breakdown products apparently remain cytotoxic to t m o r cells; (3) prolonged or repeated exposure may increase in vivo efficacy of PAM. We are currently correlating in vitro a n d v i v o conc of the parent drug and its metabolites with their cytotoxic effects.
Pediatric Research, Apr 1, 1977
Pediatric Research, Oct 1, 1979
The activation of the terminal complement components, C3-9, plays an important role in the host's... more The activation of the terminal complement components, C3-9, plays an important role in the host's defense against infection. In the present study, the ability of bacteria to activate the third component of complement (C3) in newborn serum was examined. A variety of bacteria were incubated in test sera at 37OC for 30 min and the percent of available C3 that was activated was measured. Using one strain of Esclrerchia coli (#3), 32% (mean) of the available C3 was activated in sera from 18 newborns, as compared to 85% in sera from their mothers and 79% in sera from 13 normal adults (P < 0.005). In contrast, using another strain of E. coli (N70). the percent of C3 activated in newborn sera (83%) was the same as in sera from their mothers (81%) or in sera from normal adults (73%). The defective activation of C3 in newborn sera by E. coli was not related to the presence of the K l antigen. Newborn sera were also challenged with other bacterial species and the activation of C3 was deficient when tested with klebsiellae, but not with staphylococci or streptococci. The defect in newborn sera appeared to be due to a deficiency of a serum factor rather than to the presence of an inhibitor. Speculation The defective activation of C3-9 in newborn sera by some bacteria may be, in part, responsible for the neonate's increased susceptibility to infection.
Journal of Experimental Medicine, Feb 1, 1994
We investigated whether the third component of complement (C3) is involved in the pathophysiology... more We investigated whether the third component of complement (C3) is involved in the pathophysiology of endotox~c shock, and ~f it is involved, whether it plays a protective role or whether it mediates shock and multiple organ failure. In a prospective, controUed investigation, six Brittany spaniels that were homozygous for a genetically determined deficiency of C3 (C3 deficient, <0.003% of normal serum C3 levels) and six heterozygous littermates (controls, =50% of mean normal serum C3 level) were given 2 mg/kg of reconstituted Escherichia coli 026:B6 acetone powder as a source of endotoxin, intravenously. All animals were given similar fluid and prophyhctic antibiotic therapy, and had serial hemodynamic variables obtained. After E. coli endotoxin infusion, C3-deficient animals had higher peak levels of endotoxin and less of a rise m temperature than controls (P <0.05). During the first 4 h after E. coli endotoxin infusion, C3-deficient animals had significantly greater decreases in mean central venous pressure and mean pulmonary artery pressure than controls (P <0.02). During the first 48 h after E. coli endotoxin infusion, C3deficient animals had significantly greater decreases in mean arterial pH, left ventricular ejection fraction, and mean pulmonary capillary wedge pressure, and greater increases in mean arterial lactate, arterial-alveolar O2 gradient, and transaminases (aspartate aminotransferase and alanine ammotransferase) than controls, (aU P <0.05). After E. cob endotoxin infusion, C3-ddiclent ammals compared to controls had significantly less of a decrease in mean C5 levds (P <0.01), but similar (P = NS) increases in circulating tumor necrosis factor levels, bronchoalveolar lavage nentrophils, and protein, and similar (P-NS) decreases in blood lenkocytes and platelets. Two of stx C3deficient ammals and two of six controls died. In summary, after intravenous infusion of E. coli endotoxm, canines with C3 deficiency have decreased endotoxin clearance and worse E. coli endotoxin-induced shock and organ damage. Thus, the third component of the complement system plays a beneficial role m the host defense against E. coli endotoxic shock. ,•pproximately 400,000 patients develop sepsis each year in the United States. Of these, 50% develop septic shock and multiple organ damage, which is associated with a mortality rate of 50-70% (1). In the pathogenesis of sepsis, endotoxin interacts with a number of endogenous mediators such as complement and clotting systems, bradykinin, arachidonic acid, TNF, and a variety of other cytokines (2). Each
Journal of Immunology, 1978
The xation of C3b to pneumococcal cell wall polymers as a result of activation of the alternative... more The xation of C3b to pneumococcal cell wall polymers as a result of activation of the alternative complement pathway.
Archives of Disease in Childhood, Mar 1, 1973
Clinical Infectious Diseases, 2001
Journal of Immunology, Nov 1, 1981
Cell surface sialic acid in uences tumor cell recognition in the mixed lymphocyte reaction.
Pediatric Research, Apr 1, 1974
Platelets are susceptible to immunological destruction, but the nature of the immune lesion has n... more Platelets are susceptible to immunological destruction, but the nature of the immune lesion has not been defined. Biochemistry, physiology, freeze-etching and electron microscopy were used to detect antibody induced injury. Antiserum (AS) was raised in a horse by repeated I.M. injections of glutaraldehyde fixed human platelets. Absorbtion with PPP removed non-specific activity of AS. The AS caused release of serotonin to a dilution of 1:10,000 without producing ultrastructural damage. AS stimulated aggregation in stirred C-PW to a dilution of 1:1000. Aggregates resembled those produced by collagen. Lactic dehydrogenase was not discharged by dilutions greater than 1:10. Dilutions to 1:100 caused platelet
Experimental Biology and Medicine, Jun 1, 1975
In order to investigate the role of C3 in host defense in vivo, normal AKR/J mice, genetically de... more In order to investigate the role of C3 in host defense in vivo, normal AKR/J mice, genetically deficient in C5, were depleted of serum C3 by the injection of purified cobra venom factor (CoVF). Concurrent with their C3 depletion, their serum opsonizing activity decreased to a level less than 20% of normal. When these mice were challenged with an intraperitoneal injection of pneumococci 2 hr after the CoVF treatment, the LD50 was from 30 to 80 times lower than the LD50 in saline-treated control animals. When the CoVF was given only 6 hr after the pneumococcal challenge, the LD50 was the same as in the control mice. If the pneumococci were first preopsonized in vitro and then injected into CoVF-treated animals, the LD50 was the same as that in control animals. These experiments demonstrate that C3 plays a significant role in vivo in the host's defense against infection and that a major part of that role is through its action as an opsonin. Furthermore, these experiments demonstrate that the role of C3 is most significant during the early stages of bacterial invasion.
Pediatrics, Nov 1, 2000
Objectives.To determine the immunogenicity and safety of heptavalent pneumococcal polysaccharide ... more Objectives.To determine the immunogenicity and safety of heptavalent pneumococcal polysaccharide vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) conjugated to CRM197 (7-valent conjugate pneumococcal vaccine [7VPnC]) among infants with sickle cell disease (SCD) and a comparison group of infants without SCD (non-SCD).Design.Two cohorts of infants were enrolled and received open-label doses of 7VPnC vaccine; infants enrolled before 2 months of age received 7VPnC vaccine at 2, 4, and 6 months of age followed by 23-valent pneumococcal polysaccharide vaccine (PS-23) at 24 months of age for those infants with SCD (schedule A), and infants enrolled between 2 and 12 months of age received 7VPnC at 12 months of age followed by PS-23 at 24 months of age for infants with SCD (schedule B). Safety data were collected for 3 days after each dose of vaccine. Antibody concentrations were measured to each of the 7VPnC serotypes by enzyme-linked immunosorbent assay before each vaccine dose and 1 month after the last 7VPnC dose and the PS-23 vaccine dose.Results.Forty-five infants (34 SCD and 11 non-SCD) were vaccinated according to schedule A and 16 infants (13 SCD and 3 non-SCD) according to schedule B. The 7VPnC vaccine was highly immunogenic for all serotypes among infants with and without SCD who received 3 doses of vaccine according to schedule A: depending on serotype, 89% to 100% achieved antibody concentrations above .15 μg/mL and 56% to 100% achieved antibody concentrations above 1.0 μg/mL. Among infants immunized according to schedule B, a single dose of 7VPnC vaccine resulted in antibody concentrations above .15 μg/mL in 53% to 92% by serotype and above 1.0 μg/mL in 31% to 71% by serotype. A single dose of PS-23 resulted in dramatic increases in the antibody concentrations to all serotypes regardless of 1- or 3-dose priming. There was no difference in the reactogenicity of the 7VPnC vaccine between those with and without SCD. There were no serious reactions to the 7VPnC or PS-23 vaccines, even among those with high antibody concentrations before immunization.Conclusions.Infants with SCD respond to 7VPnC vaccine with antibody concentrations that are at least as high as infants without SCD. Infants immunized with 7VPnC vaccine at 2, 4, and 6 months of age developed antibody concentrations in the same range as those achieved among infants without SCD enrolled in a large trial that demonstrated vaccine efficacy against invasive disease. Significant rises were seen in antibody concentrations to all 7VPnC serotypes after the PS-23 booster in children receiving schedule A or B.
Elsevier eBooks, 2014
Agammaglobulinemia holds a special place in the history of the primary immunodeficiency diseases.... more Agammaglobulinemia holds a special place in the history of the primary immunodeficiency diseases. It was Bruton’s original case report of a young boy with X-linked agammaglobulinemia (XLA) in 1952 that stands as the first description of a primary immunodeficiency disease. Since its original description, the molecular genetic basis of XLA, its pathophysiology, a broader description of its clinical presentation and its long-term prognosis have all been elucidated. In addition to XLA, a variety of less common causes of autosomal recessive forms of agammaglobulinemia have been identified, each of which has provided important insight into the molecules important in B-cell function.
Springer eBooks, 1988
H. influenzae, whether capsulated or not, is able to activate both the classical and alternative ... more H. influenzae, whether capsulated or not, is able to activate both the classical and alternative pathways (Anderson et al, 1972; Quinn et al, 1977) resulting in the potential to generate bactericidal and opsonising activities. Most studies have investigated these activities in relationship to type b strains because of the importance of this serotype as a cause of life-threatening invasive infections in childhood. Anderson et al (1972) showed that either purified type b capsular polysaccharide (PRP) or non-capsulated H. influenzae organisms could absorb factors from human serum which were necessary for complement dependent bactericidal activity. Subsequent studies by Steele et al used affinity purified IgG antibodies and agammaglobulinaemic human serum from which factor D and properdin had been selectively inactivated to demonstrate that H. influenzae type b could be killed through classical pathway activities mediated by antibodies to PRP. Similarly, bactericidal activity could also be demonstrated using an IgG fraction from human sera that had been pre-adsorbed with PRP to remove anticapsular antibodies. Taken together, these studies suggested that antibodies to either the PRP capsule or to cell envelope constituents are able to activate the classical pathway and generate bactericidal activity.
American Journal of Ophthalmology, Oct 1, 1977
Archives of Virology, Sep 1, 1986
ABSTRACT An inverse relationship exists between the sialic acid content of a particle and its abi... more ABSTRACT An inverse relationship exists between the sialic acid content of a particle and its ability to activate the alternative complement pathway. The present studies were performed to determine if the neuraminidase (NANase) activities of different mumps virus strains could influence the ability of mumps virus infected cells to activate the alternative pathway. CV-1 cells were infected with three different mumps virus strains (RW, O'Take, and Kilham) and after 24 hours, 10 percent guinea pig serum (GPS) treated with EGTA/MgCl2 or GPS lacking the 4th component of complement (C4DGPS) was added to the cell monolayers. After 30 minutes, the percentage C3 consumed was determined by a functional hemolytic assay. Cells infected with RW (high NANase) consumed significantly more C3 (23.2 per cent) than cells infected with Kilham (5.7 percent, low NANase). Cells infected with O'Take were intermediate in their ability to activate C3. The degree of C3 deposition on the surface of infected cells, detected by fluorescence microscopy, was also greater for cells infected with the RW than the Kilham strain of mumps virus. These studies suggest that the NANase activity of mumps virus can influence the ability of infected cells to activate the alternative pathway and thereby, the ability of complement to participate in host defense against mumps virus infection.
Journal of Immunology, Jul 1, 1978
Journal of Clinical Investigation, Dec 15, 1998
Chronic granulomatous disease (CGD) is an inherited disorder of phagocyte function in which defec... more Chronic granulomatous disease (CGD) is an inherited disorder of phagocyte function in which defective superoxide production results in deficient microbicidal activity. CGD patients suffer from recurrent, life-threatening infections, and nearly half develop chronic gastrointestinal (GI) complications (colitis, gastric outlet obstruction, or perirectal abscess) and/or autoimmune/rheumatologic disorders (AIDs). To identify genetic modifiers of disease severity, we studied a cohort of 129 CGD patients, in whom seven candidate genes (myeloperoxidase [MPO], mannose binding lectin [MBL], Fc ␥ receptors IIa, IIIa, IIIb, TNF-␣ , and IL-1 receptor antagonist), each containing a physiologically relevant polymorphism predicted to influence the host inflammatory response, were selected for analysis. Genotypes of MPO (P ϭ 0.003) and Fc ␥ RIIIb (P ϭ 0.007) were strongly associated with an increased risk for GI complications, while an Fc ␥ RIIa (P ϭ 0.05) genotype was suggestive for an association. Patients with all three associated genotypes had the highest risk for GI complications (P Ͻ 0.0001). The risk of AIDs was strongly associated with variant alleles of MBL (P ϭ 0.01) and weakly associated with an Fc ␥ RIIa genotype (P ϭ 0.04). Patients with variant forms of both MBL and Fc ␥ RIIa had the highest risk of developing an AID (P ϭ 0.003).
Pediatric Research, Apr 1, 1977
A 44 nonth old Llack female with ornohalitis at 4 davs of aoe.- .
Pediatric Research, Apr 1, 1984
We have given marrow (BM)ablative doses of PAM followed by BM autografting to children with neuro... more We have given marrow (BM)ablative doses of PAM followed by BM autografting to children with neuroblastoma (NBL), Ewing's sarcoma (ES) and osteosarcoma (0s). To examine in vitro effects of this drug, we exposed fresh and cultured NBL (6 ES (41, OS (5) and normal BM (9) cell colonies (CFU) to PAM in concentrations (conc) from 10-I to lo-' molar in a 14 day clonigenic assay. The TI2 of PAM measured by high pressure liquid chromatography was about 45 minutes. All CFU showed linear responses to PAM, correlating with both increasing drug conc and exposure duration (up to 8 hours). Fresh cells were significantly more sensitive than cultured cells. NBL-CFU were most sensitive, followed by OS, BM and ES in decreasing order. Repeat dosing up to 4 doses of PAM further inhibited CFU formation. We conclude: (1) NBL and OS CFU are more sensitive to PAM than normal BM or ES CFU; (2) PAM breakdown products apparently remain cytotoxic to t m o r cells; (3) prolonged or repeated exposure may increase in vivo efficacy of PAM. We are currently correlating in vitro a n d v i v o conc of the parent drug and its metabolites with their cytotoxic effects.
Pediatric Research, Apr 1, 1977
Pediatric Research, Oct 1, 1979
The activation of the terminal complement components, C3-9, plays an important role in the host's... more The activation of the terminal complement components, C3-9, plays an important role in the host's defense against infection. In the present study, the ability of bacteria to activate the third component of complement (C3) in newborn serum was examined. A variety of bacteria were incubated in test sera at 37OC for 30 min and the percent of available C3 that was activated was measured. Using one strain of Esclrerchia coli (#3), 32% (mean) of the available C3 was activated in sera from 18 newborns, as compared to 85% in sera from their mothers and 79% in sera from 13 normal adults (P < 0.005). In contrast, using another strain of E. coli (N70). the percent of C3 activated in newborn sera (83%) was the same as in sera from their mothers (81%) or in sera from normal adults (73%). The defective activation of C3 in newborn sera by E. coli was not related to the presence of the K l antigen. Newborn sera were also challenged with other bacterial species and the activation of C3 was deficient when tested with klebsiellae, but not with staphylococci or streptococci. The defect in newborn sera appeared to be due to a deficiency of a serum factor rather than to the presence of an inhibitor. Speculation The defective activation of C3-9 in newborn sera by some bacteria may be, in part, responsible for the neonate's increased susceptibility to infection.
Journal of Experimental Medicine, Feb 1, 1994
We investigated whether the third component of complement (C3) is involved in the pathophysiology... more We investigated whether the third component of complement (C3) is involved in the pathophysiology of endotox~c shock, and ~f it is involved, whether it plays a protective role or whether it mediates shock and multiple organ failure. In a prospective, controUed investigation, six Brittany spaniels that were homozygous for a genetically determined deficiency of C3 (C3 deficient, <0.003% of normal serum C3 levels) and six heterozygous littermates (controls, =50% of mean normal serum C3 level) were given 2 mg/kg of reconstituted Escherichia coli 026:B6 acetone powder as a source of endotoxin, intravenously. All animals were given similar fluid and prophyhctic antibiotic therapy, and had serial hemodynamic variables obtained. After E. coli endotoxin infusion, C3-deficient animals had higher peak levels of endotoxin and less of a rise m temperature than controls (P <0.05). During the first 4 h after E. coli endotoxin infusion, C3-deficient animals had significantly greater decreases in mean central venous pressure and mean pulmonary artery pressure than controls (P <0.02). During the first 48 h after E. coli endotoxin infusion, C3deficient animals had significantly greater decreases in mean arterial pH, left ventricular ejection fraction, and mean pulmonary capillary wedge pressure, and greater increases in mean arterial lactate, arterial-alveolar O2 gradient, and transaminases (aspartate aminotransferase and alanine ammotransferase) than controls, (aU P <0.05). After E. cob endotoxin infusion, C3-ddiclent ammals compared to controls had significantly less of a decrease in mean C5 levds (P <0.01), but similar (P = NS) increases in circulating tumor necrosis factor levels, bronchoalveolar lavage nentrophils, and protein, and similar (P-NS) decreases in blood lenkocytes and platelets. Two of stx C3deficient ammals and two of six controls died. In summary, after intravenous infusion of E. coli endotoxm, canines with C3 deficiency have decreased endotoxin clearance and worse E. coli endotoxin-induced shock and organ damage. Thus, the third component of the complement system plays a beneficial role m the host defense against E. coli endotoxic shock. ,•pproximately 400,000 patients develop sepsis each year in the United States. Of these, 50% develop septic shock and multiple organ damage, which is associated with a mortality rate of 50-70% (1). In the pathogenesis of sepsis, endotoxin interacts with a number of endogenous mediators such as complement and clotting systems, bradykinin, arachidonic acid, TNF, and a variety of other cytokines (2). Each
Journal of Immunology, 1978
The xation of C3b to pneumococcal cell wall polymers as a result of activation of the alternative... more The xation of C3b to pneumococcal cell wall polymers as a result of activation of the alternative complement pathway.
Archives of Disease in Childhood, Mar 1, 1973
Clinical Infectious Diseases, 2001
Journal of Immunology, Nov 1, 1981
Cell surface sialic acid in uences tumor cell recognition in the mixed lymphocyte reaction.
Pediatric Research, Apr 1, 1974
Platelets are susceptible to immunological destruction, but the nature of the immune lesion has n... more Platelets are susceptible to immunological destruction, but the nature of the immune lesion has not been defined. Biochemistry, physiology, freeze-etching and electron microscopy were used to detect antibody induced injury. Antiserum (AS) was raised in a horse by repeated I.M. injections of glutaraldehyde fixed human platelets. Absorbtion with PPP removed non-specific activity of AS. The AS caused release of serotonin to a dilution of 1:10,000 without producing ultrastructural damage. AS stimulated aggregation in stirred C-PW to a dilution of 1:1000. Aggregates resembled those produced by collagen. Lactic dehydrogenase was not discharged by dilutions greater than 1:10. Dilutions to 1:100 caused platelet
Experimental Biology and Medicine, Jun 1, 1975
In order to investigate the role of C3 in host defense in vivo, normal AKR/J mice, genetically de... more In order to investigate the role of C3 in host defense in vivo, normal AKR/J mice, genetically deficient in C5, were depleted of serum C3 by the injection of purified cobra venom factor (CoVF). Concurrent with their C3 depletion, their serum opsonizing activity decreased to a level less than 20% of normal. When these mice were challenged with an intraperitoneal injection of pneumococci 2 hr after the CoVF treatment, the LD50 was from 30 to 80 times lower than the LD50 in saline-treated control animals. When the CoVF was given only 6 hr after the pneumococcal challenge, the LD50 was the same as in the control mice. If the pneumococci were first preopsonized in vitro and then injected into CoVF-treated animals, the LD50 was the same as that in control animals. These experiments demonstrate that C3 plays a significant role in vivo in the host's defense against infection and that a major part of that role is through its action as an opsonin. Furthermore, these experiments demonstrate that the role of C3 is most significant during the early stages of bacterial invasion.
Pediatrics, Nov 1, 2000
Objectives.To determine the immunogenicity and safety of heptavalent pneumococcal polysaccharide ... more Objectives.To determine the immunogenicity and safety of heptavalent pneumococcal polysaccharide vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) conjugated to CRM197 (7-valent conjugate pneumococcal vaccine [7VPnC]) among infants with sickle cell disease (SCD) and a comparison group of infants without SCD (non-SCD).Design.Two cohorts of infants were enrolled and received open-label doses of 7VPnC vaccine; infants enrolled before 2 months of age received 7VPnC vaccine at 2, 4, and 6 months of age followed by 23-valent pneumococcal polysaccharide vaccine (PS-23) at 24 months of age for those infants with SCD (schedule A), and infants enrolled between 2 and 12 months of age received 7VPnC at 12 months of age followed by PS-23 at 24 months of age for infants with SCD (schedule B). Safety data were collected for 3 days after each dose of vaccine. Antibody concentrations were measured to each of the 7VPnC serotypes by enzyme-linked immunosorbent assay before each vaccine dose and 1 month after the last 7VPnC dose and the PS-23 vaccine dose.Results.Forty-five infants (34 SCD and 11 non-SCD) were vaccinated according to schedule A and 16 infants (13 SCD and 3 non-SCD) according to schedule B. The 7VPnC vaccine was highly immunogenic for all serotypes among infants with and without SCD who received 3 doses of vaccine according to schedule A: depending on serotype, 89% to 100% achieved antibody concentrations above .15 μg/mL and 56% to 100% achieved antibody concentrations above 1.0 μg/mL. Among infants immunized according to schedule B, a single dose of 7VPnC vaccine resulted in antibody concentrations above .15 μg/mL in 53% to 92% by serotype and above 1.0 μg/mL in 31% to 71% by serotype. A single dose of PS-23 resulted in dramatic increases in the antibody concentrations to all serotypes regardless of 1- or 3-dose priming. There was no difference in the reactogenicity of the 7VPnC vaccine between those with and without SCD. There were no serious reactions to the 7VPnC or PS-23 vaccines, even among those with high antibody concentrations before immunization.Conclusions.Infants with SCD respond to 7VPnC vaccine with antibody concentrations that are at least as high as infants without SCD. Infants immunized with 7VPnC vaccine at 2, 4, and 6 months of age developed antibody concentrations in the same range as those achieved among infants without SCD enrolled in a large trial that demonstrated vaccine efficacy against invasive disease. Significant rises were seen in antibody concentrations to all 7VPnC serotypes after the PS-23 booster in children receiving schedule A or B.
Elsevier eBooks, 2014
Agammaglobulinemia holds a special place in the history of the primary immunodeficiency diseases.... more Agammaglobulinemia holds a special place in the history of the primary immunodeficiency diseases. It was Bruton’s original case report of a young boy with X-linked agammaglobulinemia (XLA) in 1952 that stands as the first description of a primary immunodeficiency disease. Since its original description, the molecular genetic basis of XLA, its pathophysiology, a broader description of its clinical presentation and its long-term prognosis have all been elucidated. In addition to XLA, a variety of less common causes of autosomal recessive forms of agammaglobulinemia have been identified, each of which has provided important insight into the molecules important in B-cell function.
Springer eBooks, 1988
H. influenzae, whether capsulated or not, is able to activate both the classical and alternative ... more H. influenzae, whether capsulated or not, is able to activate both the classical and alternative pathways (Anderson et al, 1972; Quinn et al, 1977) resulting in the potential to generate bactericidal and opsonising activities. Most studies have investigated these activities in relationship to type b strains because of the importance of this serotype as a cause of life-threatening invasive infections in childhood. Anderson et al (1972) showed that either purified type b capsular polysaccharide (PRP) or non-capsulated H. influenzae organisms could absorb factors from human serum which were necessary for complement dependent bactericidal activity. Subsequent studies by Steele et al used affinity purified IgG antibodies and agammaglobulinaemic human serum from which factor D and properdin had been selectively inactivated to demonstrate that H. influenzae type b could be killed through classical pathway activities mediated by antibodies to PRP. Similarly, bactericidal activity could also be demonstrated using an IgG fraction from human sera that had been pre-adsorbed with PRP to remove anticapsular antibodies. Taken together, these studies suggested that antibodies to either the PRP capsule or to cell envelope constituents are able to activate the classical pathway and generate bactericidal activity.
American Journal of Ophthalmology, Oct 1, 1977
Archives of Virology, Sep 1, 1986
ABSTRACT An inverse relationship exists between the sialic acid content of a particle and its abi... more ABSTRACT An inverse relationship exists between the sialic acid content of a particle and its ability to activate the alternative complement pathway. The present studies were performed to determine if the neuraminidase (NANase) activities of different mumps virus strains could influence the ability of mumps virus infected cells to activate the alternative pathway. CV-1 cells were infected with three different mumps virus strains (RW, O'Take, and Kilham) and after 24 hours, 10 percent guinea pig serum (GPS) treated with EGTA/MgCl2 or GPS lacking the 4th component of complement (C4DGPS) was added to the cell monolayers. After 30 minutes, the percentage C3 consumed was determined by a functional hemolytic assay. Cells infected with RW (high NANase) consumed significantly more C3 (23.2 per cent) than cells infected with Kilham (5.7 percent, low NANase). Cells infected with O'Take were intermediate in their ability to activate C3. The degree of C3 deposition on the surface of infected cells, detected by fluorescence microscopy, was also greater for cells infected with the RW than the Kilham strain of mumps virus. These studies suggest that the NANase activity of mumps virus can influence the ability of infected cells to activate the alternative pathway and thereby, the ability of complement to participate in host defense against mumps virus infection.