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2.
Artigo em Inglês | MEDLINE | ID: mdl-31238161

RESUMO

BACKGROUND: LPS-responsive beige-like anchor (LRBA) deficiency presents with susceptibility to infections, autoimmunity, and lymphoproliferation. The long-term efficacy of cytotoxic T-lymphocyte-associated antigen 4-immunoglobulin (abatacept) as targeted therapy for its immune dysregulatory features remains to be established. OBJECTIVE: To determine the clinical and immunologic features of LRBA deficiency and long-term efficacy of abatacept treatment in controlling the different disease manifestations. METHODS: Twenty-two LRBA-deficient patients were recruited from different immunology centers and followed prospectively. Eighteen patients on abatacept were evaluated every 3 months for long-term clinical and immunologic responses. LRBA expression, lymphocyte subpopulations, and circulating T follicular helper cells were determined by flow cytometry. RESULTS: The mean age of the patients was 13.4 ± 7.9 years, and the follow-up period was 3.4 ± 2.3 years. Recurrent infections (n = 19 [86.4%]), immune dysregulation (n = 18 [81.8%]), and lymphoproliferation (n = 16 [72.7%]) were common clinical features. The long-term benefits of abatacept in 16 patients were demonstrated by complete control of lymphoproliferation and chronic diarrhea followed by immune dysregulation, most notably autoimmune cytopenias. Weekly or every other week administration of abatacept gave better disease control compared with every 4 weeks. There were no serious side effects related to the abatacept therapy. Circulating T follicular helper cell frequencies were found to be a reliable biomarker of disease activity, which decreased on abatacept therapy in most subjects. However, high circulating T follicular helper cell frequencies persisted in 2 patients who had a more severe disease phenotype that was relatively resistant to abatacept therapy. CONCLUSIONS: Long-term abatacept therapy is effective in most patients with LRBA deficiency.

3.
J Clin Immunol ; 39(3): 316-323, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30924026

RESUMO

Severe combined immunodeficiency (SCID) is the most serious PID, characterized by T cell lymphopenia and lack of antigen-specific T cell and B cell immune responses, inevitably leading to death within the first year of life if hematopoietic stem cell transplantation (HSCT) is not performed. PURPOSE AND METHODS: Since SCID is a common type of PID with an estimated incidence of 1/10.000 in Turkey, a retrospective analysis of HSCT characteristics, survival, immune recovery, and the major clinical features of SCID prior to HSCT is the aim of this multi-transplant center-based analysis. RESULTS: A total of 234 SCID patients transplanted between the years 1994 and 2014 were included in the study. Median age at diagnosis was 5 months, at transplantation, 7 months, B- phenotype and RAGs were the most common defects among others. Immune phenotype did not seem to have an effect on survival rate (p > 0.05), Immunoglobulin (Ig) requirement following HSCT did not differ between B+ and B- phenotypes (p > 0.05). Overall survival rate was 65.7% over a period of 20 years. It increased from 54% (1994-2004) to 69% (p = 0.052) during the last 10 years (2005-2014). Ten-year survival after HSCT has improved over time although the difference was not significant. Infection at the time of transplantation (p = 0.006), mismatched related donor (MMRD) (haploidentical parents), and matched unrelated donor (MUD) donor transplants p < 0.001 were the most important factors, significantly affecting the outcome. CONCLUSIONS: This is the first multicenter study with the largest data obtained from transplanted SCID patients in Turkey. Early diagnosis with newborn screening (NBS) together with emerging referrals, treatment by transplantation centers, and specialized teams are mandatory in countries with high parental consanguinity such as Turkey.

4.
J Pediatr Hematol Oncol ; 40(8): e547-e549, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29620677

RESUMO

Ataxia-telangiectasia (A-T) is a multisystem disease caused by a genetic defect located on the long arm of chromosome 11 (11p22-23). The gene defect results in the loss of A-T-mutated protein, subsequently leading to unrepaired DNA fractures and defects in the signal transduction pathway. As a result, characteristic findings arise, including recurrent sinopulmonary infections, hypersensitivity against ionized radiation with the tendency to develop cancer related to progressive cerebellar ataxia, pathognomonic oculocutaneous telangiectasias, varying degrees of humoral and cellular immunodeficiency, and infertility. This case report presents a 3-year-old male patient with A-T who developed hemophagocytic syndrome. To the best of our knowledge, no such case has been previously reported.

5.
Turk J Haematol ; 34(4): 345-349, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28404538

RESUMO

Hematopoietic stem cell transplantation is a promising curative therapy for many combined primary immunodeficiencies and phagocytic disorders. We retrospectively reviewed pediatric cases of patients diagnosed with primary immunodeficiencies and scheduled for hematopoietic stem cell transplantation. We identified 22 patients (median age, 6 months; age range, 1 month to 10 years) with various diagnoses who received hematopoietic stem cell transplantation. The patient diagnoses included severe combined immunodeficiency (n=11), Chediak-Higashi syndrome (n=2), leukocyte adhesion deficiency (n=2), MHC class 2 deficiency (n=2), chronic granulomatous syndrome (n=2), hemophagocytic lymphohistiocytosis (n=1), Wiskott-Aldrich syndrome (n=1), and Omenn syndrome (n=1). Of the 22 patients, 7 received human leukocyte antigen-matched related hematopoietic stem cell transplantation, 12 received haploidentical hematopoietic stem cell transplantation, and 2 received matched unrelated hematopoietic stem cell transplantation. The results showed that 5 patients had graft failure. Fourteen patients survived, yielding an overall survival rate of 67%. Screening newborn infants for primary immunodeficiency diseases may result in timely administration of hematopoietic stem cell transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes de Imunodeficiência/terapia , Síndrome de Chediak-Higashi/epidemiologia , Síndrome de Chediak-Higashi/terapia , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/epidemiologia , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/terapia , Humanos , Síndromes de Imunodeficiência/epidemiologia , Lactente , Síndrome da Aderência Leucocítica Deficitária/epidemiologia , Síndrome da Aderência Leucocítica Deficitária/terapia , Linfo-Histiocitose Hemofagocítica/epidemiologia , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Imunodeficiência Combinada Severa/epidemiologia , Imunodeficiência Combinada Severa/terapia , Análise de Sobrevida , Turquia/epidemiologia , Síndrome de Wiskott-Aldrich/epidemiologia , Síndrome de Wiskott-Aldrich/terapia
6.
Pediatr Allergy Immunol ; 28(5): 446-451, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28452068

RESUMO

BACKGROUND: Serum vitamin D levels have not been studied in children with seasonal allergic rhinitis (SAR). The aim of this study was to evaluate the vitamin D levels of children with SAR and to compare them to levels in healthy children during pollen season. METHODS: This study was conducted in 100 children with SAR and 100 healthy controls. Clinical and laboratory evaluations and vitamin D analyses of all the participants were performed between the months of April and July. Pollen sensitization was detected in the patient group using a skin prick test. 25(OH)D3 levels were compared between the patient and control groups. Associations among the patient 25(OH)D3 levels and their demographic, clinical, and laboratory characteristics were analyzed. RESULTS: Overall, 72% of the patients were male, the median age was 12.35 years (range: 6-17.8 years), and the median body mass index value was 19.15 (range: 13.6-27.8). There were no differences between the patients and healthy controls in terms of gender, age, or body mass index. The mean levels of 25(OH)D3 (20.78±6) in patients were higher than those of the controls (17.92±4). In the patient group, no associations were found among 25(OH)D3 levels, demographic characteristics, atopy test results, atopy history, severity of rhinitis, and the total four symptoms score (all P>.05). CONCLUSIONS: During pollen season, children with SAR may have higher vitamin D levels than healthy controls. The presence of asthma and/or atopic dermatitis in addition to SAR did not change this result.


Assuntos
Rinite Alérgica Sazonal/sangue , Vitamina D/análogos & derivados , Adolescente , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Rinite Alérgica Sazonal/complicações , Rinite Alérgica Sazonal/diagnóstico , Rinite Alérgica Sazonal/imunologia , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/etiologia
7.
Am J Med Genet A ; 170(12): 3253-3257, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27604394

RESUMO

ICF syndrome is a primary immunodeficiency disease characterized by hypo- or agammaglobulinemia, centromeric instability mainly on chromosomes 1, 9, and 16 and facial anomalies. ICF syndrome presents with frequent respiratory tract infections in infancy. A 20-month-old female patient was referred to our clinic due to frequent lower respiratory tract infections. ICF syndrome was considered because of comorbidity of hypogammaglobulinemia, facial anomalies, and neuromotor growth retardation. Metaphase chromosome analysis revealed centromeric instability on chromosomes 1, 9, and 16 and through Sanger a previously unreported homozygous missense mutation (c.1805T>C; [p.V602A]) was identified in the DNMT3B, confirming ICF1. The patient was found to have a breakdown in renal function 1 year later; the urinary system was examined and bilateral vesicoureteral reflux was found, warranting the need for dialysis in time. This report expands the mutation spectrum of ICF1 and is the first to describe bilateral vesicoureteral reflux accompanying ICF syndrome. © 2016 Wiley Periodicals, Inc.


Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/genética , Mutação , Insuficiência Renal/diagnóstico , Insuficiência Renal/etiologia , Refluxo Vesicoureteral/complicações , Biomarcadores , Instabilidade Cromossômica , Aberrações Cromossômicas , Análise Mutacional de DNA , Facies , Feminino , Estudos de Associação Genética , Humanos , Imunoglobulinas Intravenosas , Síndromes de Imunodeficiência/tratamento farmacológico , Lactente , Linhagem , Fenótipo , Exame Físico , Síndrome , Refluxo Vesicoureteral/diagnóstico
8.
Pediatr Allergy Immunol ; 27(1): 78-82, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26360812

RESUMO

BACKGROUND: The cause and pathophysiology of PFAPA syndrome is unknown. The aim of this study was to determine all MEFV gene variants relevant to familial Mediterranean fever in children with PFAPA syndrome. METHODS: All MEFV gene variants were analyzed in patients with PFAPA syndrome. All patients were evaluated using the Gaslini scoring system. Serum immunoglobulin levels were also determined upon admission. RESULTS: We evaluated 64 patients with PFAPA syndrome. The median age at diagnosis was 37.5 (min-max: 6-96) months, and the percentage of male patients was 55.0%. The Gaslini diagnostic score for periodic fever was high in 81.0% of the patients. An MEFV gene mutation was found in 42 (66.0%) children. Mostly, heterozygous or compound heterozygous variants of the MEFV gene were found. Two patients were homozygous for R202Q. MEFV gene mutations were not detected in 22 (34.0%) patients. No significant differences in clinical or laboratory findings were observed between the two groups (p > 0.05), and there were no significant differences in period and duration of the fever episodes (p > 0.05). The fever of all 47 patients (100.0%) who received prednisolone during the episodes decreased within hours and did not recur. Eighteen of the patients using prednisolone underwent prophylaxis with colchicine, and the fever episodes of 9/18 (50.0%) patients using colchicine decreased within months. CONCLUSIONS: Most patients presenting with PFAPA syndrome have heterozygous MEFV gene mutations. Whether carrying a heterozygous MEFV gene is the primary cause of this syndrome requires further investigation.


Assuntos
Proteínas do Citoesqueleto/genética , Febre Familiar do Mediterrâneo/genética , Linfadenite/genética , Mutação , Faringite/genética , Estomatite Aftosa/genética , Anti-Inflamatórios/uso terapêutico , Biomarcadores/sangue , Criança , Pré-Escolar , Colchicina/uso terapêutico , Análise Mutacional de DNA , Febre Familiar do Mediterrâneo/sangue , Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/tratamento farmacológico , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Glucocorticoides/uso terapêutico , Heterozigoto , Homozigoto , Humanos , Imunoglobulina G/sangue , Lactente , Linfadenite/sangue , Linfadenite/diagnóstico , Linfadenite/tratamento farmacológico , Masculino , Faringite/sangue , Faringite/diagnóstico , Faringite/tratamento farmacológico , Fenótipo , Prednisolona/uso terapêutico , Pirina , Estudos Retrospectivos , Fatores de Risco , Estomatite Aftosa/sangue , Estomatite Aftosa/diagnóstico , Estomatite Aftosa/tratamento farmacológico , Síndrome , Resultado do Tratamento
9.
Immunol Rev ; 264(1): 103-20, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25703555

RESUMO

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey.


Assuntos
Suscetibilidade a Doenças/imunologia , Predisposição Genética para Doença , Hospedeiro Imunocomprometido , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/etiologia , Mycobacterium tuberculosis/imunologia , Tuberculose/etiologia , Fatores Etários , Criança , Genes Dominantes , Genes Recessivos , Humanos , Síndromes de Imunodeficiência/diagnóstico , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
10.
Clin Respir J ; 9(4): 497-500, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24798948

RESUMO

Pulmonary hypoplasia is characterized by decrease in the number and size of pulmonary airways, alveoli and vessels. In autopsy, pulmonary hypoplasia is a major cause of death in neonates and infants. The disease is usually diagnosed in childhood period. Although it mimics lung parenchymal disease and other vascular abnormalities radiologically, it is easily recognized with computed tomography angiography and magnetic resonance angiography examinations. In 50% of patients, concomitant cardiovascular, neuromuscular, gastrointestinal tract, and urogenital anomalies are also available. There are two types of pulmonary hypoplasia: primary and secondary. Primary unilateral pulmonary hypoplasia may be asymptomatic and the tendency for bronchopulmonary infections is often increased in children. In this case report, a 22-month-old male patient characterized by recurrent infections and recurrent wheezes in infantile period, whose episodes of wheezing regressed after the pulmonectomy, was presented.


Assuntos
Anormalidades Múltiplas/fisiopatologia , Anormalidades Múltiplas/cirurgia , Pneumopatias/fisiopatologia , Pneumopatias/cirurgia , Pulmão/anormalidades , Sons Respiratórios/fisiopatologia , Anormalidades Múltiplas/diagnóstico por imagem , Hospitalização/tendências , Humanos , Recém-Nascido , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Pulmão/cirurgia , Pneumopatias/diagnóstico por imagem , Masculino , Pneumonectomia , Sons Respiratórios/etiologia , Resultado do Tratamento , Adulto Jovem
12.
Neurology ; 83(21): 1888-97, 2014 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-25339207

RESUMO

OBJECTIVE: To determine the proportion of children with herpes simplex encephalitis (HSE) displaying TLR3 deficiency, the extent of TLR3 allelic heterogeneity, and the specific clinical features of TLR3 deficiency. METHODS: We determined the sequence of all exons of TLR3 in 110 of the 120 patients with HSE enrolled in our study who do not carry any of the previously described HSE-predisposing mutations of TLR3 pathway genes (TLR3, UNC93B1, TRIF, TRAF3, and TBK1). All the new mutant TLR3 alleles detected were characterized experimentally in-depth to establish the causal relationship between the genotype and phenotype. RESULTS: In addition to the 3 previously reported TLR3-deficient patients from the same cohort, 6 other children or young adults with HSE carry 1 of 5 unique or extremely rare (minor allele frequency <0.001) missense TLR3 alleles. Two alleles (M374T, D592N) heterozygous in 3 patients are not deleterious in vitro. The other 3 are deleterious via different mechanisms: G743D+R811I and L360P heterozygous in 2 patients are loss-of-function due to low levels of expression and lack of cleavage, respectively, and R867Q homozygous in 1 patient is hypomorphic. The 3 patients' fibroblasts display impaired TLR3 responses and enhanced herpes simplex virus 1 susceptibility. Overall, TLR3 deficiency is therefore found in 6 (5%) of the 120 patients studied. There is high allelic heterogeneity, with 3 forms of autosomal dominant partial defect by negative dominance or haploinsufficiency, and 2 forms of autosomal recessive defect with complete or partial deficiency. Finally, 4 (66%) of the 6 TLR3-deficient patients had at least 1 late relapse of HSE, whereas relapse occurred in only 12 (10%) of the total cohort of 120 patients. CONCLUSIONS: Childhood-onset HSE is due to TLR3 deficiency in a traceable fraction of patients, in particular the ones with HSE recurrence. Mutations in TLR3 and TLR3 pathway genes should be searched and experimentally studied in children with HSE, and patients with proven TLR3 deficiency should be followed carefully.


Assuntos
Encefalite por Herpes Simples/diagnóstico , Encefalite por Herpes Simples/genética , Frequência do Gene/genética , Mutação/genética , Receptor 3 Toll-Like/deficiência , Receptor 3 Toll-Like/genética , Adolescente , Células Cultivadas , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Linhagem , Recidiva , Fatores de Risco
13.
Clin Immunol ; 154(2): 105-11, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25064839

RESUMO

Heterozygous mutations in the NLRP12 gene have been found in patients with systemic auto-inflammatory diseases. However, the NLRP12-associated periodic fever syndromes show a wide clinical spectrum, including patients without classical diagnostic symptoms. Here, we report on a 20-year-old female patient diagnosed with common variable immunodeficiency (CVID), who developed intestinal amyloidosis and carried novel compound heterozygous mutations in NLRP12, identified by whole exome and transcriptome sequencing. CVID is a primary immunodeficiency characterized by low serum immunoglobulins, recurrent bacterial infections and development of malignancy, but it also presents with a magnitude of autoimmune features. Because of the unspecific heterogeneous clinical features of the disease, a delay in diagnosis is common. Secondary, inflammatory (AA type) amyloidosis has infrequently been observed in CVID patients. Based on our case observation and a critical review of the literature, we suggest that NLRP12 mutations might account for a small fraction of CVID patients with severe auto-inflammatory complications.


Assuntos
Amiloidose/genética , Imunodeficiência de Variável Comum/genética , Regulação da Expressão Gênica/fisiologia , Enteropatias/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Amiloidose/imunologia , Amiloidose/metabolismo , Imunodeficiência de Variável Comum/imunologia , Imunodeficiência de Variável Comum/metabolismo , Feminino , Humanos , Enteropatias/imunologia , Enteropatias/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Mutação , RNA/genética , RNA/metabolismo , Adulto Jovem
14.
J Allergy Clin Immunol ; 133(4): 1134-41, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24679470

RESUMO

BACKGROUND: Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. OBJECTIVES: We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. METHODS: An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. RESULTS: Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≤1 month) showed an increased prevalence of complications (P = .006) and death caused by BCG-associated complications (P < .0001). The odds of experiencing complications among patients with T-cell numbers of 250/µL or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P = .001) than among those with T-cell numbers of greater than 250/µL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P < .0001). CONCLUSIONS: BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.


Assuntos
Vacina BCG/efeitos adversos , Imunodeficiência Combinada Severa/epidemiologia , Vacina BCG/imunologia , Pré-Escolar , Comorbidade , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Prevalência , Estudos Retrospectivos , Risco , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/terapia , Vacinação/efeitos adversos , Vacinação/legislação & jurisprudência
15.
Acta Orthop Traumatol Turc ; 48(6): 628-34, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25637726

RESUMO

OBJECTIVE: The aim of this study was to investigate Legg-Calvé-Perthes disease (PD) pathogenesis by comparing absolute circulating endothelial progenitor cell (EPC) counts, serum levels of vascular endothelial growth factor-A (VEGF-A) and immunoglobulins between PD patients and controls. METHODS: The study included 28 PD cases (mean age: 8 ± 3.8) and 25 healthy age-matched control subjects. EPC, serum VEGF-A and immunoglobulin levels were measured in peripheral blood samples. Comparisons and correlation analysis were performed. RESULTS: In the PD group, 17 subjects were in the fragmentation stage and 11 in the healing stage. Four patients had bilateral disease and 14 had hypogammaglobulinemia. Median EPC count of the PD group was 80 and was significantly higher than those of the control group (p=0.011). No significant difference was determined in serum VEGF-A levels (p=0.354). EPC count were inversely correlated with serum IgG levels of the PD group (r=0.403, p=0.03). Absolute EPC count was also significantly higher in the fragmentation stage than in the healing stage and were also greater in bilaterally affected than in unilaterally affected patients. Circulating EPC count was correlated to the serum VEGF-A levels in patients with fragmentation stage of PD (r=0.605, p=0.01) and in those with hypogammaglobulinemia (r=0.599, p=0.001). CONCLUSION: High EPC count at the fragmentation stage of PD and relatively higher counts in bilateral disease suggest that EPC may be a valuable marker in the diagnosis and follow-up of PD. Additional studies are needed to explain the strong correlation between EPC and serum VEGF-A level in the fragmentation stage and in the presence of hypogammaglobulinemia.


Assuntos
Agamaglobulinemia/diagnóstico , Células Progenitoras Endoteliais/metabolismo , Doença de Legg-Calve-Perthes/sangue , Doença de Legg-Calve-Perthes/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/sangue , Agamaglobulinemia/epidemiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Progressão da Doença , Feminino , Seguimentos , Humanos , Doença de Legg-Calve-Perthes/terapia , Masculino , Valor Preditivo dos Testes , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Fatores de Tempo
16.
J Allergy Clin Immunol ; 132(5): 1156-1163.e5, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23910690

RESUMO

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder of phagocytes resulting in impaired killing of bacteria and fungi. A mutation in one of the 4 genes encoding the components p22(phox), p47(phox), p67(phox), and p40(phox) of the leukocyte nicotinamide dinucleotide phosphate reduced (NADPH) oxidase leads to autosomal recessive (AR) CGD. A mutation in the CYBB gene encoding gp91(phox) leads to X-linked recessive CGD. OBJECTIVE: The aim of this study is to show the correlation between clinical, functional, and genetic data of patients with CGD from Turkey. METHODS: We report here the results of 89 patients with CGD from 73 Turkish families in a multicenter study. RESULTS: Most of the families (55%) have an AR genotype, and 38% have an X-linked genotype; patients from 5 families with a suspected AR genotype (7%) were not fully characterized. We compared patients with CGD according to the severity of NADPH oxidase deficiency of neutrophils. Patients with A22(0), A67(0) or X91(0) phenotypes with a stimulation index of 1.5 or less have early clinical presentation and younger age at diagnosis (mean, 3.2 years). However, in p47(phox)-deficient cases and in 5 other AR cases with high residual oxidase activity (stimulation index ≥ 3), later and less severe clinical presentation and older age at diagnosis (mean, 7.1 years) were found. Pulmonary involvement was the most common clinical feature, followed by lymphadenitis and abscesses. CONCLUSION: Later and less severe clinical presentation and older age at diagnosis are related to the residual NADPH oxidase activity of neutrophils and not to the mode of inheritance. CGD caused by A22(0) and A67(0) subtypes manifests as severe as the X91(0) subtype.


Assuntos
Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/genética , Causas de Morte , Pré-Escolar , Ativação Enzimática , Feminino , Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/mortalidade , Humanos , Incidência , Infecção/etiologia , Masculino , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Neutrófilos/metabolismo , Análise de Sequência de DNA
17.
J Pediatr Hematol Oncol ; 35(8): e335-7, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23389499

RESUMO

We report a RAG2-deficient patient with severe combined immunodeficiency and hemophagocytic bone marrow aplasia with plasma cells after a nonconditioned transplantation from a fully matched sibling. After engraftment, disseminated BCGosis appeared because of graft versus host disease prophylaxis. On the 55th day, eosinophilia, neutropenia, and thrombocytopenia developed. Aplasia, hemophagocytic histiocytes, and plasma cells were found on his bone marrow with very high level of serum immunoglobulin E. We could not discriminate exactly whether BCGosis or alloimmune response is the cause of hemophagocytic aplasia with plasma cells. Despite the second hematopoietic stem cell transplantation with a reduced intensity conditioning regime, his marrow aplasia did not recover and he died. This case suggests that BCGosis might be associated with hemophagocytic marrow aplasia with plasma cells in an alloimmune reaction.


Assuntos
Vacina BCG/efeitos adversos , Doenças da Medula Óssea/etiologia , Proteínas de Ligação a DNA/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfo-Histiocitose Hemofagocítica/etiologia , Proteínas Nucleares/genética , Imunodeficiência Combinada Severa/cirurgia , Vacina BCG/imunologia , Doenças da Medula Óssea/patologia , Humanos , Lactente , Linfo-Histiocitose Hemofagocítica/patologia , Masculino , Plasmócitos/patologia , Imunodeficiência Combinada Severa/genética , Condicionamento Pré-Transplante , Transplante Homólogo/efeitos adversos
18.
Pediatr Transplant ; 16(5): 451-7, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22594916

RESUMO

SCID is characterized by profound deficiencies of T and B lymphocytes. HSCT is the only curative treatment for children with SCID. The clinical characteristics and outcome of 30 HLA-haploidentical transplantations in 18 patients (15 SCID, two Omenn syndrome, and one MHC Class II deficiency) are reported here. The age of patients at diagnosis ranged from one and half to nine months (median: four months). The median time was one month between the diagnosis and the time of the initial transplantation. Infused CD34+ stem cell dose was ranged between 7 and 94.2 × 10(6) /kg. Nine of 18 patients were found to be positive for CMV antigenemia at diagnosis; therefore, none of them received a conditioning regimen. The most common complication was graft failure (61%), so repeated transplantations (two to four) were performed in seven patients. The mean time of lymphoid engraftment was 17.5 days (median: 16, range: 11-29 days). Ten of 15 SCID (67%) patients survived with a stable complete donor chimerism. However, all three non-SCID patients died. In conclusion, in the absence of a matched family donor, HLA-haploidentical transplantation from parental donors represents a readily available treatment option especially for patients with SCID, offering a high chance of cure.


Assuntos
Antígenos HLA/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Histocompatibilidade , Imunodeficiência Combinada Severa/cirurgia , Seleção do Doador , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Humanos , Lactente , Masculino , Pais , Complicações Pós-Operatórias/epidemiologia , Reoperação/estatística & dados numéricos , Imunodeficiência Combinada Severa/imunologia , Imunodeficiência Combinada Severa/mortalidade , Taxa de Sobrevida , Resultado do Tratamento
19.
Retin Cases Brief Rep ; 6(1): 7-10, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-25390698

RESUMO

PURPOSE: To report a child with sarcoid choroidopathy that has a similar appearance to birdshot chorioretinopathy. METHODS: Observational case report. Review of the clinical examination, laboratory findings, and histopathologic records of a child with sarcoidosis. RESULTS: A 9-year-old girl was examined in a routine consultation demand in our pediatric clinic. Slit-lamp examination revealed granulomatous anterior uveitis, and funduscopic examination of both eyes revealed numerous, oval, irregular, creamy chorioretinal lesions. These were widespread throughout the fundus, except the macula, and had the characteristic funduscopic appearance of birdshot chorioretinopathy. The patient underwent axillary lymph node biopsy that showed noncaseating granulomas consistent with sarcoidosis. CONCLUSION: Sarcoidosis should be considered in a child with chorioretinal lesions resembling birdshot chorioretinopathy.

20.
Indian J Pediatr ; 78(10): 1234-8, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21394591

RESUMO

OBJECTIVE: To evaluate whether the mode of delivery (vaginal versus C-section) influences the levels of CD4+CD25+FOXP3+ Treg cells in cord blood and maternal peripheral blood and also to examine its relationship with plasma cortisol levels. METHODS: Newborns either born vaginally (n = 19) or via elective C- section (n = 20) and their mothers, as well as 20 healthy but not pregnant women, were included in the study. CD4+CD25+FOXP3 (Treg) cells were examined by flow cytometry. Total lymphocyte counts (TLC) and serum cortisol levels were also determined for all the groups. RESULTS: The percentages of CD4+CD25+FOXP3 cells and the serum cortisol levels of infants born vaginally (p < 0.004 and p < 0.0001) and their mothers (p < 0.0001 for both) were found to be significantly higher than those of newborns born by C-section and their mothers. Positive correlations were seen between CD4+CD25+FOXP3+ cells (r = 0.741) and serum cortisol levels (r = 0.468). No relationship was observed between newborns delivered by C-section and their mothers (r = 0.022 for both). CONCLUSIONS: This study suggests that mode of delivery affects cord blood Treg cells. Higher CD4+CD25+FOXP3+ Treg cells of newborns and their mothers in vaginal delivery group and their relationship with serum cortisol levels suggest a stress phenomenon related to vaginal delivery.


Assuntos
Cesárea , Parto Obstétrico , Sangue Fetal/citologia , Linfócitos T Reguladores/citologia , Feminino , Fatores de Transcrição Forkhead/sangue , Humanos , Hidrocortisona/sangue , Recém-Nascido , Gravidez
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