Dewton M Vasconcelos | Universidade de São Paulo (original) (raw)

Papers by Dewton M Vasconcelos

Scientific Investigation in Dentistry, Jan 29, 2015

Viruses

Currently, there are no evidence-based treatment options for long COVID-19, and it is known that ... more Currently, there are no evidence-based treatment options for long COVID-19, and it is known that SARS-CoV-2 can persist in part of the infected patients, especially those with immunosuppression. Since there is a robust secretion of SARS-CoV-2-specific highly-neutralizing IgA antibodies in breast milk, and because this immunoglobulin plays an essential role against respiratory virus infection in mucosa cells, being, in addition, more potent in neutralizing SARS-CoV-2 than IgG, here we report the clinical course of an NFκB-deficient patient chronically infected with the SARS-CoV-2 Gamma variant, who, after a non-full effective treatment with plasma infusion, received breast milk from a vaccinated mother by oral route as treatment for COVID-19. After such treatment, the symptoms improved, and the patient was systematically tested negative for SARS-CoV-2. Thus, we hypothesize that IgA and IgG secreted antibodies present in breast milk could be useful to treat persistent SARS-CoV-2 infec...

Clinics, 2006

PURPOSE: To study and compare the appearance of hairs from patients with Chédiak-Higashi and Gris... more PURPOSE: To study and compare the appearance of hairs from patients with Chédiak-Higashi and Griscelli-Prunieras syndromes under light and polarized light microscopy. METHOD: Hairs from 2 Chédiak-Higashi and 2 Griscelli-Prunieras patients were obtained and examined under normal and polarized light microscopy. RESULTS: Under light microscopy, hairs from Chédiak-Higashi patients presented evenly distributed, regular melanin granules, larger than those seen in normal hairs. Under polarized light microscopy, shafts exhibited a bright and polychromatic refringence appearance. In contrast, hair from Griscelli-Prunieras patients, under light microscopy, exhibited bigger and irregular melanin granules, distributed mainly near the medulla. Under polarized light microscopy, shafts appeared monotonously white. CONCLUSION: Light microscopic examination of hair shafts of patients with Chédiak-Higashi or Griscelli-Prunieras syndrome reveals subtle differences that are useful in identifying both disorders, but not in distinguishing between them. We provide evidence that polarized light microscopy of hair shafts, an approach that has not been previously described, aids in differentiating between these syndromes. We propose hair study by polarized light microscopy as a helpful complementary diagnostic method for differential diagnosis between CHS and GPS, especially when the more sophisticated molecular studies are not available.

Scandinavian Journal of Immunology, 2008

We identified a 4-year-old Brazilian boy from a family of Japanese descent and history of consang... more We identified a 4-year-old Brazilian boy from a family of Japanese descent and history of consanguinity, who suffered from severe recurrent pneumonia. He carries factor H (FH) deficiency associated with reduced levels of component C9 and low serum levels of C3 and factor B. His mother also presented low levels of these proteins and factor I, while his father and sister had only lower levels of FH. Western blot assays confirmed the complete absence of FH and FHL-1 polypeptides in this patient. Sequencing of the proband's FH cDNA revealed a homozygous G453A substitution, encoding an Arg(127)His change. His mother, father and sister are heterozygous for this substitution. Despite the absence of FH in the plasma, this protein was detected in the patient's fibroblasts, suggesting that Arg(127) may be important for FH secretion. Low concentrations of C9 were detected in the proband serum but no mutations in the patient's C9 gene or promoter have been identified, suggesting that this is a consequence of uncontrolled complement activation and high C9 consumption.

Scandinavian Journal of Immunology, 2009

Type 1, X-linked Hyper-IgM syndrome (HIGM1) is caused by mutations in the gene encoding the CD154... more Type 1, X-linked Hyper-IgM syndrome (HIGM1) is caused by mutations in the gene encoding the CD154 protein, also known as CD40 ligand (CD40LG). CD40L is expressed in activated T cells and interacts with CD40 receptor expressed on B lymphocytes and dendritic cells. Affected patients present cellular and humoral immune defects, with infections by intracellular, opportunistic and extracellular pathogens. In the present study we investigated the molecular defects underlying disease in four patients with HIGM1. We identified four distinct CD40L mutations, two of them which have not been previously described. P1 harboured the novel p.G227X mutation which abolished CD40L expression. P2 had a previously described frame shift deletion in exon 2 (p.I53fsX65) which also prevented protein expression. P3 demonstrated the previously known p.V126D change in exon 4, affecting the TNF homology (TNFH) domain. Finally, P4 evidenced the novel p.F229L mutation also located in the TNFH domain. In silico analysis of F229L predicted the change to be pathological, affecting the many hydrophobic interactions of this residue. Precise molecular diagnosis in HIGM syndrome allows reliable detection of carriers, making genetic counselling and prenatal diagnosis possible.

New England Journal of Medicine, 2011

Background The genetic analysis of human primary immunodeficiencies has defined the contribution ... more Background The genetic analysis of human primary immunodeficiencies has defined the contribution of specific cell populations and molecular pathways in the host defense against infection. Disseminated infection caused by bacille Calmette-Guérin (BCG) vaccines is an early manifestation of primary immunodeficiencies, such as severe combined immunodeficiency. In many affected persons, the cause of disseminated BCG disease is unexplained.

Molecular Immunology, 2007

Molecular Immunology, 2007

Molecular Immunology, 2007

Medical Mycology, 2009

Chronic mucocutaneous candidiasis (CMC) is a rare disease associated with immunodeficiency and ch... more Chronic mucocutaneous candidiasis (CMC) is a rare disease associated with immunodeficiency and characterized by persistent and refractory infections of the skin, appendages and mucous membranes caused by members of the genus Candida. Several different disorders are classified under this common denominator, including chronic and recurrent mucocutaneous infections due to Candida spp., which are sometimes linked to autoimmune endocrinopathies. These fungal infections are usually confined to the mucocutaneous surface, with little propensity for systemic disease or septicemia. We describe a patient with CMC who had an esophageal candidiasis refractory to treatment for decades and who developed an epidermoid esophageal cancer. No risk factors such as familiar susceptibility, smoking, alcohol drinking, or living in an endemic area were verified. This case report suggests the participation of nitrosamine compounds produced by chronic Candida infections as a risk factor for esophageal cancer in a patient with autosomal-dominant chronic mucocutaneous candidiasis.

Journal of the European Academy of Dermatology and Venereology, 2012

Background Hereditary Angio-oedema (HAE) is a serious medical condition caused by a rare autosoma... more Background Hereditary Angio-oedema (HAE) is a serious medical condition caused by a rare autosomal dominant genetic disorder, in which C1 inhibitor (C1-INH) function is reduced. There is no organized information on the HAE patient population in Brazil. Objective The Brazilian Registry was established to disseminate diagnostic access, and to better understand the main features of the disease in our country and its clinical impact. Methods A questionnaire was prepared and sent to specialists. The completed questionnaires were forwarded to the coordinating site and then entered into the Registry. Samples from patients with an unconfirmed diagnosis were tested for C1 inhibitor and C4 levels. Results From 2006 to 2010, 210 patients (133 females; mean age, 30 ±17 years) were included. The median age of onset of symptoms and age at diagnosis were 6.5 and 21 years, respectively; 80.9% of the patients had subcutaneous oedema, 54% gastrointestinal and 35.7% respiratory symptoms (21% had laryngeal oedema). Laparotomy due to the disease was performed in 6.2% of the patients. The majority of patients had Type I HAE of moderate severity. Twenty-seven per cent did not receive treatment; 53% were treated with danazol alone. Conclusion A paucity of patients with Type II HAE and a high frequency of laparotomy were observed, highlighting the need for better diagnosis in Brazil. HAE related educational activities, improved diagnosis and access to available therapy are needed in Brazil.

Clinical Infectious Diseases, 2005

See the article by Zerbe and Holland on pages e38-41) Background. Paracoccidioides brasiliensis i... more See the article by Zerbe and Holland on pages e38-41) Background. Paracoccidioides brasiliensis is a facultative intracellular dimorphic fungus that causes paracoccidioidomycosis (PCM), the most important deep mycosis in Latin America. Only a small percentage of individuals infected by P. brasiliensis develop clinical PCM, possibly in part because of genetically determined interindividual variability of host immunity. However, no primary immunodeficiency has ever been associated with PCM. Methods. We describe the first patient, to our knowledge, with PCM and a well-defined primary immunodeficiency in the b1 subunit of the interleukin (IL)-12/IL-23 receptor, a disorder previously shown to be specifically associated with impaired interferon (IFN)-g production, mycobacteriosis, and salmonellosis. Results. Our patient had a childhood history of bacille Calmette-Guérin disease and nontyphoid salmonellosis and, at the age of 20 years, presented to our clinic with a disseminated (acute) form of PCM. He responded well to antifungal treatment and is now doing well at 24 years of age. Conclusions. This unique observation supports previous studies of PCM suggesting that IL-12, IL-23, and IFN-g play an important role in protective immunity to P. brasiliensis. Tuberculosis and PCM are thus not only related clinically and pathologically, but also by their immunological pathogenesis. Our study further expands the spectrum of clinical manifestations of inherited defects of the IL-12/IL-23-IFN-g axis. Patients with unexplained deep fungal infections, such as PCM, should be tested for defects in the IL-12/IL-23-IFN-g axis.

Clinical Immunology, 2009

study, we evaluate the use of the Biomek series of liquid handlers integrated with a plate centri... more study, we evaluate the use of the Biomek series of liquid handlers integrated with a plate centrifuge to facilitate automated 96 well plate sample preparation for flow cytometry analysis in a high-throughput capacity. Fundamental steps such as transfer of antibody solutions, samples (whole blood and cell lines), permeabilizing and fixative reagents to plates, sample centrifugation, and cell washing were independently characterized for accuracy, reproducibility, cell recovery, and wash efficiency. Overall performance for the automated processes was assessed by comparing results to those of manual procedures of surface and intracellular staining of both stimulated whole blood and cell lines, specifically focusing on CD3, CD4, CD8, IFN-γ, and IL-2. This evaluation showed comparable (R2 N .95) results for manual and automated processes, at a throughput of about 96 wells in less than 3 hours (about 15 minutes of operator interaction).

Clinical Immunology, 2009

Clinical Immunology, 2009

IFN-γ is a pro-inflammatory cytokine, but is also required for induction of tolerance in numerous... more IFN-γ is a pro-inflammatory cytokine, but is also required for induction of tolerance in numerous models. Thus, liver allografts in WT mice achieves long-term survival, but none graft survives N 14 days in IFN-γ b s N-/- .

Clinical Immunology, 2006

We report the incidence of gy lymphocytoses in patients presenting with primary immunodeficiency.... more We report the incidence of gy lymphocytoses in patients presenting with primary immunodeficiency. The study included 13 children (8 male, 5 female, age range 4-180 months). 5 had a genetically defined immunodeficiency (T-B-NK+SCID, Omenn's syndrome, JAK-3 deficiency, XLP and RAG-SCID). The remaining 8 had undefined immunodeficiency. In all cases the TCR gy cells were z 20% of the CD3 positive population, with normal or elevated counts of gy lymphocytes and an ah lymphopenia. Lymphocyte proliferation responses were poor, while immunoglobulin levels and antibody responses were variable. Clonal TCRG and TCRD gene rearrangements were identified using BIOMED-2 primers in 4/5 cases in the group with defined immunodeficiency and in 3/8 cases in the group with undefined immunodeficiency. Individual TCRD primers were used to identify specific full TCRD gene usage. TCRVD1/JD1 was the most common gene rearrangement in contrast to peripheral blood of healthy individuals where TCRVD2/JD1 is the most frequent gene recombination. TCR ah cells were polyclonal in all cases. In 2 cases with clonal TCRGD gene rearrangements expanded Vh9 and 20 families were identified respectively. TCR gy lymphocytoses has been described in response to infections such as tuberculosis, EBV, HIV as well as in the context of malignancies and autoimmune disease. In primary immunodeficiency normal or elevated levels of gy cells may occur independently of abnormalities in the normal maturation process affecting TCR ah cells. The incidence of gy clones may also provide an independent marker of undefined immunodeficiency.

Clinical Immunology, 2006

Clinical Immunology, 2009

demonstrated in idiopathic juvenile arthritis. IL-6 and IL-2 in vitreous could explain the ocular... more demonstrated in idiopathic juvenile arthritis. IL-6 and IL-2 in vitreous could explain the ocular clinical features observed. The genetic analysis showed a new NOD2 mutation. Acknowledgments: CONACyT 71291, Fundacion Conde de Valenciana.

Allergy & Clinical Immunology International - Journal of the World Allergy Organization, 2002

Annals of the New York Academy of Sciences, 2011

Hematopoietic stem cell transplantation (HSCT) is now highly successfully curing a widening range... more Hematopoietic stem cell transplantation (HSCT) is now highly successfully curing a widening range of primary immunodeficiencies (PIDs). Better tissue typing, matching of donors, less toxic chemotherapy, better virus detection and treatment, improved supportive care, and graft-versus-host disease prophylaxis mean up to a 90% cure for severe combined immunodeficiency patients and a 70-80% cure for other PIDs given a matched unrelated donor, and rising to 95% for young patients with specific PIDs, such as Wiskott-Aldrich syndrome. Precise molecular diagnosis, detailed data on prognosis, and careful pre-HSCT assessment of infective lung and liver damage will ensure an informed benefit analysis of HSCT and the best outcome. It is now recognized that the best treatment option for chronic granulomatous disease is HSCT, which can also be curative for CD40 ligand deficiency and complex immune dysregulation disorders.

Scientific Investigation in Dentistry, Jan 29, 2015

Viruses

Currently, there are no evidence-based treatment options for long COVID-19, and it is known that ... more Currently, there are no evidence-based treatment options for long COVID-19, and it is known that SARS-CoV-2 can persist in part of the infected patients, especially those with immunosuppression. Since there is a robust secretion of SARS-CoV-2-specific highly-neutralizing IgA antibodies in breast milk, and because this immunoglobulin plays an essential role against respiratory virus infection in mucosa cells, being, in addition, more potent in neutralizing SARS-CoV-2 than IgG, here we report the clinical course of an NFκB-deficient patient chronically infected with the SARS-CoV-2 Gamma variant, who, after a non-full effective treatment with plasma infusion, received breast milk from a vaccinated mother by oral route as treatment for COVID-19. After such treatment, the symptoms improved, and the patient was systematically tested negative for SARS-CoV-2. Thus, we hypothesize that IgA and IgG secreted antibodies present in breast milk could be useful to treat persistent SARS-CoV-2 infec...

Clinics, 2006

PURPOSE: To study and compare the appearance of hairs from patients with Chédiak-Higashi and Gris... more PURPOSE: To study and compare the appearance of hairs from patients with Chédiak-Higashi and Griscelli-Prunieras syndromes under light and polarized light microscopy. METHOD: Hairs from 2 Chédiak-Higashi and 2 Griscelli-Prunieras patients were obtained and examined under normal and polarized light microscopy. RESULTS: Under light microscopy, hairs from Chédiak-Higashi patients presented evenly distributed, regular melanin granules, larger than those seen in normal hairs. Under polarized light microscopy, shafts exhibited a bright and polychromatic refringence appearance. In contrast, hair from Griscelli-Prunieras patients, under light microscopy, exhibited bigger and irregular melanin granules, distributed mainly near the medulla. Under polarized light microscopy, shafts appeared monotonously white. CONCLUSION: Light microscopic examination of hair shafts of patients with Chédiak-Higashi or Griscelli-Prunieras syndrome reveals subtle differences that are useful in identifying both disorders, but not in distinguishing between them. We provide evidence that polarized light microscopy of hair shafts, an approach that has not been previously described, aids in differentiating between these syndromes. We propose hair study by polarized light microscopy as a helpful complementary diagnostic method for differential diagnosis between CHS and GPS, especially when the more sophisticated molecular studies are not available.

Scandinavian Journal of Immunology, 2008

We identified a 4-year-old Brazilian boy from a family of Japanese descent and history of consang... more We identified a 4-year-old Brazilian boy from a family of Japanese descent and history of consanguinity, who suffered from severe recurrent pneumonia. He carries factor H (FH) deficiency associated with reduced levels of component C9 and low serum levels of C3 and factor B. His mother also presented low levels of these proteins and factor I, while his father and sister had only lower levels of FH. Western blot assays confirmed the complete absence of FH and FHL-1 polypeptides in this patient. Sequencing of the proband's FH cDNA revealed a homozygous G453A substitution, encoding an Arg(127)His change. His mother, father and sister are heterozygous for this substitution. Despite the absence of FH in the plasma, this protein was detected in the patient's fibroblasts, suggesting that Arg(127) may be important for FH secretion. Low concentrations of C9 were detected in the proband serum but no mutations in the patient's C9 gene or promoter have been identified, suggesting that this is a consequence of uncontrolled complement activation and high C9 consumption.

Scandinavian Journal of Immunology, 2009

Type 1, X-linked Hyper-IgM syndrome (HIGM1) is caused by mutations in the gene encoding the CD154... more Type 1, X-linked Hyper-IgM syndrome (HIGM1) is caused by mutations in the gene encoding the CD154 protein, also known as CD40 ligand (CD40LG). CD40L is expressed in activated T cells and interacts with CD40 receptor expressed on B lymphocytes and dendritic cells. Affected patients present cellular and humoral immune defects, with infections by intracellular, opportunistic and extracellular pathogens. In the present study we investigated the molecular defects underlying disease in four patients with HIGM1. We identified four distinct CD40L mutations, two of them which have not been previously described. P1 harboured the novel p.G227X mutation which abolished CD40L expression. P2 had a previously described frame shift deletion in exon 2 (p.I53fsX65) which also prevented protein expression. P3 demonstrated the previously known p.V126D change in exon 4, affecting the TNF homology (TNFH) domain. Finally, P4 evidenced the novel p.F229L mutation also located in the TNFH domain. In silico analysis of F229L predicted the change to be pathological, affecting the many hydrophobic interactions of this residue. Precise molecular diagnosis in HIGM syndrome allows reliable detection of carriers, making genetic counselling and prenatal diagnosis possible.

New England Journal of Medicine, 2011

Background The genetic analysis of human primary immunodeficiencies has defined the contribution ... more Background The genetic analysis of human primary immunodeficiencies has defined the contribution of specific cell populations and molecular pathways in the host defense against infection. Disseminated infection caused by bacille Calmette-Guérin (BCG) vaccines is an early manifestation of primary immunodeficiencies, such as severe combined immunodeficiency. In many affected persons, the cause of disseminated BCG disease is unexplained.

Molecular Immunology, 2007

Molecular Immunology, 2007

Molecular Immunology, 2007

Medical Mycology, 2009

Chronic mucocutaneous candidiasis (CMC) is a rare disease associated with immunodeficiency and ch... more Chronic mucocutaneous candidiasis (CMC) is a rare disease associated with immunodeficiency and characterized by persistent and refractory infections of the skin, appendages and mucous membranes caused by members of the genus Candida. Several different disorders are classified under this common denominator, including chronic and recurrent mucocutaneous infections due to Candida spp., which are sometimes linked to autoimmune endocrinopathies. These fungal infections are usually confined to the mucocutaneous surface, with little propensity for systemic disease or septicemia. We describe a patient with CMC who had an esophageal candidiasis refractory to treatment for decades and who developed an epidermoid esophageal cancer. No risk factors such as familiar susceptibility, smoking, alcohol drinking, or living in an endemic area were verified. This case report suggests the participation of nitrosamine compounds produced by chronic Candida infections as a risk factor for esophageal cancer in a patient with autosomal-dominant chronic mucocutaneous candidiasis.

Journal of the European Academy of Dermatology and Venereology, 2012

Background Hereditary Angio-oedema (HAE) is a serious medical condition caused by a rare autosoma... more Background Hereditary Angio-oedema (HAE) is a serious medical condition caused by a rare autosomal dominant genetic disorder, in which C1 inhibitor (C1-INH) function is reduced. There is no organized information on the HAE patient population in Brazil. Objective The Brazilian Registry was established to disseminate diagnostic access, and to better understand the main features of the disease in our country and its clinical impact. Methods A questionnaire was prepared and sent to specialists. The completed questionnaires were forwarded to the coordinating site and then entered into the Registry. Samples from patients with an unconfirmed diagnosis were tested for C1 inhibitor and C4 levels. Results From 2006 to 2010, 210 patients (133 females; mean age, 30 ±17 years) were included. The median age of onset of symptoms and age at diagnosis were 6.5 and 21 years, respectively; 80.9% of the patients had subcutaneous oedema, 54% gastrointestinal and 35.7% respiratory symptoms (21% had laryngeal oedema). Laparotomy due to the disease was performed in 6.2% of the patients. The majority of patients had Type I HAE of moderate severity. Twenty-seven per cent did not receive treatment; 53% were treated with danazol alone. Conclusion A paucity of patients with Type II HAE and a high frequency of laparotomy were observed, highlighting the need for better diagnosis in Brazil. HAE related educational activities, improved diagnosis and access to available therapy are needed in Brazil.

Clinical Infectious Diseases, 2005

See the article by Zerbe and Holland on pages e38-41) Background. Paracoccidioides brasiliensis i... more See the article by Zerbe and Holland on pages e38-41) Background. Paracoccidioides brasiliensis is a facultative intracellular dimorphic fungus that causes paracoccidioidomycosis (PCM), the most important deep mycosis in Latin America. Only a small percentage of individuals infected by P. brasiliensis develop clinical PCM, possibly in part because of genetically determined interindividual variability of host immunity. However, no primary immunodeficiency has ever been associated with PCM. Methods. We describe the first patient, to our knowledge, with PCM and a well-defined primary immunodeficiency in the b1 subunit of the interleukin (IL)-12/IL-23 receptor, a disorder previously shown to be specifically associated with impaired interferon (IFN)-g production, mycobacteriosis, and salmonellosis. Results. Our patient had a childhood history of bacille Calmette-Guérin disease and nontyphoid salmonellosis and, at the age of 20 years, presented to our clinic with a disseminated (acute) form of PCM. He responded well to antifungal treatment and is now doing well at 24 years of age. Conclusions. This unique observation supports previous studies of PCM suggesting that IL-12, IL-23, and IFN-g play an important role in protective immunity to P. brasiliensis. Tuberculosis and PCM are thus not only related clinically and pathologically, but also by their immunological pathogenesis. Our study further expands the spectrum of clinical manifestations of inherited defects of the IL-12/IL-23-IFN-g axis. Patients with unexplained deep fungal infections, such as PCM, should be tested for defects in the IL-12/IL-23-IFN-g axis.

Clinical Immunology, 2009

study, we evaluate the use of the Biomek series of liquid handlers integrated with a plate centri... more study, we evaluate the use of the Biomek series of liquid handlers integrated with a plate centrifuge to facilitate automated 96 well plate sample preparation for flow cytometry analysis in a high-throughput capacity. Fundamental steps such as transfer of antibody solutions, samples (whole blood and cell lines), permeabilizing and fixative reagents to plates, sample centrifugation, and cell washing were independently characterized for accuracy, reproducibility, cell recovery, and wash efficiency. Overall performance for the automated processes was assessed by comparing results to those of manual procedures of surface and intracellular staining of both stimulated whole blood and cell lines, specifically focusing on CD3, CD4, CD8, IFN-γ, and IL-2. This evaluation showed comparable (R2 N .95) results for manual and automated processes, at a throughput of about 96 wells in less than 3 hours (about 15 minutes of operator interaction).

Clinical Immunology, 2009

Clinical Immunology, 2009

IFN-γ is a pro-inflammatory cytokine, but is also required for induction of tolerance in numerous... more IFN-γ is a pro-inflammatory cytokine, but is also required for induction of tolerance in numerous models. Thus, liver allografts in WT mice achieves long-term survival, but none graft survives N 14 days in IFN-γ b s N-/- .

Clinical Immunology, 2006

We report the incidence of gy lymphocytoses in patients presenting with primary immunodeficiency.... more We report the incidence of gy lymphocytoses in patients presenting with primary immunodeficiency. The study included 13 children (8 male, 5 female, age range 4-180 months). 5 had a genetically defined immunodeficiency (T-B-NK+SCID, Omenn's syndrome, JAK-3 deficiency, XLP and RAG-SCID). The remaining 8 had undefined immunodeficiency. In all cases the TCR gy cells were z 20% of the CD3 positive population, with normal or elevated counts of gy lymphocytes and an ah lymphopenia. Lymphocyte proliferation responses were poor, while immunoglobulin levels and antibody responses were variable. Clonal TCRG and TCRD gene rearrangements were identified using BIOMED-2 primers in 4/5 cases in the group with defined immunodeficiency and in 3/8 cases in the group with undefined immunodeficiency. Individual TCRD primers were used to identify specific full TCRD gene usage. TCRVD1/JD1 was the most common gene rearrangement in contrast to peripheral blood of healthy individuals where TCRVD2/JD1 is the most frequent gene recombination. TCR ah cells were polyclonal in all cases. In 2 cases with clonal TCRGD gene rearrangements expanded Vh9 and 20 families were identified respectively. TCR gy lymphocytoses has been described in response to infections such as tuberculosis, EBV, HIV as well as in the context of malignancies and autoimmune disease. In primary immunodeficiency normal or elevated levels of gy cells may occur independently of abnormalities in the normal maturation process affecting TCR ah cells. The incidence of gy clones may also provide an independent marker of undefined immunodeficiency.

Clinical Immunology, 2006

Clinical Immunology, 2009

demonstrated in idiopathic juvenile arthritis. IL-6 and IL-2 in vitreous could explain the ocular... more demonstrated in idiopathic juvenile arthritis. IL-6 and IL-2 in vitreous could explain the ocular clinical features observed. The genetic analysis showed a new NOD2 mutation. Acknowledgments: CONACyT 71291, Fundacion Conde de Valenciana.

Allergy & Clinical Immunology International - Journal of the World Allergy Organization, 2002

Annals of the New York Academy of Sciences, 2011

Hematopoietic stem cell transplantation (HSCT) is now highly successfully curing a widening range... more Hematopoietic stem cell transplantation (HSCT) is now highly successfully curing a widening range of primary immunodeficiencies (PIDs). Better tissue typing, matching of donors, less toxic chemotherapy, better virus detection and treatment, improved supportive care, and graft-versus-host disease prophylaxis mean up to a 90% cure for severe combined immunodeficiency patients and a 70-80% cure for other PIDs given a matched unrelated donor, and rising to 95% for young patients with specific PIDs, such as Wiskott-Aldrich syndrome. Precise molecular diagnosis, detailed data on prognosis, and careful pre-HSCT assessment of infective lung and liver damage will ensure an informed benefit analysis of HSCT and the best outcome. It is now recognized that the best treatment option for chronic granulomatous disease is HSCT, which can also be curative for CD40 ligand deficiency and complex immune dysregulation disorders.