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1.
Pediatr Hematol Oncol ; : 1-5, 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30346863

RESUMO

INTRODUCTION: Severe congenital neutropenia (SCN) includes a group of genetic disorders which cause to arrest of neutrophil maturation. SCN can be associated with heterogenous group of genetic defects in ELANE, GFI1, HAX1, G6PC3, JAGN1, VPS45 or activating mutations in the Wiskott-Aldrich syndrome (WAS) gene. AIM: Here we report a patient who has a HAX1 mutation presented with cyclic manner. CASE REPORT: A 6 year old female patients was admitted with recurrent apthous stomatitis. We followed the patient as cyclic neutropenia according to complete blood count results 2 times for 6 weeks. After persistant neutropenia developed during a severe varicella infection, we analysed HAX1 mutation, the result was interesting and incompatible with reported cyclic neutropenia patients. CONCLUSION: We suggest that HAX1 deficiency should be thought in patients who have normal neutrophil counts in the between of infections.

2.
Artigo em Inglês | MEDLINE | ID: mdl-29906526

RESUMO

BACKGROUND: V(D)J recombination ensures the diversity of the adaptive immune system. Although its complete defect causes severe combined immunodeficiency (ie, T-B- severe combined immunodeficiency), its suboptimal activity is associated with a broad spectrum of immune manifestations, such as late-onset combined immunodeficiency and autoimmunity. The earliest molecular diagnosis of these patients is required to adopt the best therapy strategy, particularly when it involves a myeloablative conditioning regimen for hematopoietic stem cell transplantation. OBJECTIVE: We aimed at developing biomarkers based on analysis of the T-cell receptor (TCR) α repertoire to assist in the diagnosis of patients with primary immunodeficiencies with V(D)J recombination and DNA repair deficiencies. METHODS: We used flow cytometric (fluorescence-activated cell sorting) analysis to quantify TCR-Vα7.2-expressing T lymphocytes in peripheral blood and developed PROMIDISα, a multiplex RT-PCR/next-generation sequencing assay, to evaluate a subset of the TCRα repertoire in T lymphocytes. RESULTS: The combined fluorescence-activated cell sorting and PROMIDISα analyses revealed specific signatures in patients with V(D)J recombination-defective primary immunodeficiencies or ataxia telangiectasia/Nijmegen breakage syndromes. CONCLUSION: Analysis of the TCRα repertoire is particularly appropriate in a prospective way to identify patients with partial immune defects caused by suboptimal V(D)J recombination activity, a DNA repair defect, or both. It also constitutes a valuable tool for the retrospective in vivo functional validation of variants identified through exome or panel sequencing. Its broader implementation might be of interest to assist early diagnosis of patients presenting with hypomorphic DNA repair defects inclined to experience acute toxicity during prehematopoietic stem cell transplantation conditioning.

3.
J Clin Immunol ; 38(3): 273-277, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29564582

RESUMO

PURPOSE: Adenosine deaminase 2 (ADA2) have been reported to cause vasculitic diseases and immunodeficiency recently. Patients present with stroke episodes and rashes mimicking polyarteritis nodosa (PAN). We report a patient who has been followed up with severe neutropenia and found an unexpectedly revealed novel mutation in CECR1 affecting ADA2. METHODS: We reviewed medical records and clinical history of the patient. No mutations in other known neutropenia genes such as ELA, G6PC3, HAX1, AP3B1, LAMTOR2, VPS13B, VPS45, GFI1, JAGN1, or WAS could be detected. Sanger sequencing was used to confirm the genetic variants in the patient and relatives. RESULTS: Genetic analysis by exome sequencing revealed a novel mutation in the gene CECR1 (c.G962A; p.G321E) which segregated perfectly in the relatives. CONCLUSION: This is the first DADA2 patient presenting with severe neutropenia. We suggest that in patients with unexplained cytopenias combined with immunodeficiency, fevers of unknown origin and high inflammation markers, DADA2 should be considered.

5.
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
6.
Case Rep Pediatr ; 2014: 614238, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24511403

RESUMO

Artemis, DNA ligase IV, DNA protein kinase catalytic subunit, and Cernunnos/XLF genes in nonhomologous end joining pathways of DNA repair mechanisms have been identified as responsible for radiosensitive SCID. Here, we present a 3-year-old girl patient with severe growth retardation, bird-like face, recurrent perianal abscess, pancytopenia, and polydactyly. Firstly, she was thought as Fanconi anemia and spontaneous DNA breaks were seen on chromosomal analysis. After that DEB test was found to be normal and Fanconi anemia was excluded. Because of that she had low IgG and IgA levels, normal IgM level, and absence of B cells in peripheral blood; she was considered as primary immunodeficiency, Nijmegen breakage syndrome. A mutation in NBS1 gene was not found; then Cernunnos/XLF deficiency was investigated due to clinical similarities with previously reported cases. Homozygous mutation in Cernunnos/XLF gene (NHEJ1) was identified. She is now on regular IVIG prophylaxis and has no new infection. Fully matched donor screening is in progress for bone marrow transplantation which is curative treatment of the disease. In conclusion, the patients with microcephaly, bird-like face, and severe growth retardation should be evaluated for hypogammaglobulinemia and primary immunodeficiency diseases.

7.
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
8.
Exp Clin Transplant ; 9(5): 349-52, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21967264

RESUMO

X-linked Hyper IgM is characterized by an absence of the CD40 ligand on activated T lymphocytes resulting in defects of both cellular and humoral immunity. Patients usually present with recurrent bacterial and opportunistic infections. Chronic liver disease is seen in about 75% of patients as a complication. Here, we report a 3.5-year-old boy with X-linked Hyper IgM referred to our clinic for bone marrow transplant. He was transplanted from an HLA-identical sibling donor using a new conditioning agent, treosulphan, together with cyclophosphamide. Since 6 months of age, he has had recurrent respiratory infections, and his XHIGM was diagnosed when he was 1.5 years old. The diagnosis was confirmed by sequence analysis of the CD40L gene. On physical examination, growth failure, bilateral fine crackles in both lungs, and hepatosplenomegaly were detected. The results of his liver function tests were abnormal, and a liver biopsy showed grade III fibrosis and compensated cirrhosis. After conditioning with treosulphan (12 g/m(2)/d x 3 d) and cyclophosphamide (50 mg/kg/d x 4 d), bone marrow from his HLA-identical sister was infused. CD40L expression on activated lymphocytes of the patient was 84% on day +21. His posttransplant period was uneventful. He is now at posttransplant 2 years, with full donor chimerism, and mild, chronic, graft-versus-host disease on his tongue. In conclusion, treosulphan is a new agent for conditioning regimen with less toxicity in patients with severe liver disease.


Assuntos
Transplante de Medula Óssea , Bussulfano/análogos & derivados , Ligante de CD40/deficiência , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/cirurgia , Cirrose Hepática/cirurgia , Agonistas Mieloablativos/uso terapêutico , Condicionamento Pré-Transplante/métodos , Biópsia , Transplante de Medula Óssea/efeitos adversos , Bussulfano/efeitos adversos , Bussulfano/uso terapêutico , Pré-Escolar , Ciclofosfamida/uso terapêutico , Teste de Histocompatibilidade , Humanos , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/imunologia , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/patologia , Cirrose Hepática/imunologia , Cirrose Hepática/patologia , Masculino , Agonistas Mieloablativos/efeitos adversos , Índice de Gravidade de Doença , Fatores de Tempo , Condicionamento Pré-Transplante/efeitos adversos , Resultado do Tratamento
9.
Pediatr Transplant ; 14(6): E79-82, 2010 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-19344339

RESUMO

HC is a common complication following HSCT. Risk factors include viral infections, cyclophosphamide and busulfan usage, pelvic irradiation, older age at transplantation, allogeneic HSCT and GvHD. The severity of HC ranges from mild hematuria to life-threatening bleeding. Here, we present a seven-and-a-half-yr-old boy with Wiskott-Aldrich syndrome who experienced a late onset Grade III hemorrhagic cystitis following HSCT from his fully matched sibling. A Grade I GvHD localized to skin developed on day +11 and prednisolone therapy was given between the 11th and 22nd d. Myeloid and platelet engraftments were achieved +13 and +16 d, respectively. A gross hematuria began on the 21st post-transplant day. The urine cultures for bacterial or fungal organisms were negative. Urine analysis by PCR revealed a CMV viruria. Following systemic ganciclovir treatment, urinary CMV became negative but hemorrhagic cystitis did not improve. Due to the probability of existing BK virus or adenovirus, two doses of cidofovir were administered intravesically. As he continued to have painful hematuria with large clot formations, two doses of intravesical hyaluronic acid were applied. Macroscopic hematuria resolved within four d after the second dose. Complete remission was achieved on day +77. Finally, intravesical administration of hyaluronic acid seems to be effective and safe and can be a promising treatment in patients suffering from severe and late onset HC.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Cistite/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hematúria/etiologia , Ácido Hialurônico/administração & dosagem , Síndrome de Wiskott-Aldrich/tratamento farmacológico , Administração Intravesical , Antivirais/uso terapêutico , Criança , Cidofovir , Citosina/análogos & derivados , Citosina/uso terapêutico , Humanos , Masculino , Organofosfonatos/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/epidemiologia , Fatores de Tempo
10.
Pediatr Int ; 51(5): 661-5, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19419517

RESUMO

BACKGROUND: Croup, which is seen commonly in childhood, is a disorder that can be recurrent and progress to bronchial asthma. In the present study the prevalence of gastroesophageal reflux (GER) and atopy and the response to therapy were investigated in children with recurrent croup. METHODS: Between October 2003 and June 2004, 57 patients with acute stridor were admitted to the emergency room. The patients who had at least three croup episodes and patients with first croup episode were compared. RESULTS: Thirty-two children had recurrent croup history, GER was found in of 62.5%, and atopy in 17.2%. Atopy was not found in any children with first croup episode. The difference was significant. In addition it was found that atopic dermatitis, previous history of wheezing and established atopy increased the risk of croup recurrence. Alone or combined inhaled corticosteroids and GER therapy were administered, and 77.7% of the patients responded very well. CONCLUSION: GER and atopy should be investigated in patients with recurrent spasmodic croup. Recurrent croup is a non-specific manifestation of atopy. Patients with atopy should be followed closely for developing bronchial asthma.


Assuntos
Crupe/epidemiologia , Refluxo Gastroesofágico/epidemiologia , Hipersensibilidade Imediata/epidemiologia , Pré-Escolar , Comorbidade , Crupe/diagnóstico , Crupe/tratamento farmacológico , Feminino , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/tratamento farmacológico , Humanos , Hipersensibilidade Imediata/diagnóstico , Lactente , Masculino , Recidiva , Fatores de Risco , Resultado do Tratamento
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