RESUMO
BACKGROUND: X-linked agammaglobulinemia (XLA) is characterized by the absence of immunoglobulin and B cells. Patients suffer from recurrent bacterial infections from early childhood, and require lifelong immunoglobulin replacement therapy. Mutations in BTK (Bruton's Tyrosine Kinase) are associated with this phenotype. Some patients that present XLA do not show typical clinical symptoms, resulting in delayed diagnosis due to the lack of a severe phenotype. This study presents a report of five XLA patients from four different families and attempts to determine a relationship between delayed diagnosis and the occurrence of BTK mutations. METHODS: Samples from patients with antibody deficiency were analyzed to determine BTK expression, immunophenotyping and mutation analysis. Clinical and laboratory data was analyzed and presented for each patient. RESULTS: Most patients presented here showed atypical clinical and laboratory data for XLA, including normal IgM, IgG, or IgA levels. Most patients expressed detectable BTK protein. Sequencing of BTK showed that these patients harbored missense mutations in the pleckstrin homology and Src-homology-2 domains. When it was compared to public databases, BTK sequencing exhibited a new change, along with three other previously reported changes. CONCLUSIONS: Delayed diagnosis and atypical manifestations in XLA might be related to mutation type and BTK expression.
Assuntos
Agamaglobulinemia/diagnóstico , Linfócitos B/imunologia , Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Infecções/diagnóstico , Mutação de Sentido Incorreto/genética , Domínios de Homologia à Plecstrina/genética , Proteínas Tirosina Quinases/genética , Domínios de Homologia de src/genética , Adolescente , Adulto , Tirosina Quinase da Agamaglobulinemia , Criança , Pré-Escolar , Análise Mutacional de DNA , Diagnóstico Tardio , Humanos , Imunoglobulinas/sangue , Imunoglobulinas/deficiência , Imunofenotipagem , Fenótipo , Adulto JovemRESUMO
Objetivo: Descrever um caso de forma granulomatosa da imunodeficiência comum variável (ICV) enfatizando a boa evolução da doença granulomatosa durante o acompanhamento em longo prazo. Descrição do caso: Paciente do gênero feminino, atualmente com 26 anos. Apresentava história de otites e amigdalites desde os seis meses e pneumonias desde os três anos de idade. Aos cinco anos foi levada a serviço especializado: apresentava-se desnutrida e com baço palpável a 9 cm e fígado a 2 cm. A investigação laboratorial iniciada nessa ocasião mostrou deficiência de IgG, IgA, IgM séricas, ausência de isohemaglutininas, linfócitos B, T, CD4+ e CD8+ normais. A biopsia hepática revelou doença granulomatosa. Foi então diagnosticada forma granulomatosa da ICV. A paciente foi submetida ao tratamento da imunodeficiência sendo indicado esteroide para a doença granulomatosa. O acompanhamento mensal da paciente durante 21 anos mostrou boa evolução, com regressão da hepatoesplenomegalia e preservação da função hepática. Discussão: A ICV é uma deficiência primária predominantemente de anticorpos, em que há pneumonias de repetição e cujo tratamento principal é a reposição de gamaglobulina. A forma granulomatosa hepática da ICV é rara, mas deve ter diagnóstico precoce, na tentativa de preservar a função hepática. No presente caso, durante os 21 anos de acompanhamento, houve boa evolução da forma granulomatosa da imunodeficiência com o uso de baixas doses de esteroides.
Objective: To describe a case of granulomatous form of common variable immunodeficiency (CVID) with good progress during a longterm monitoring. Case report: Female patient, now 26. She had a history of ear infections and tonsillitis since she was six months and pneumonia as from the age of three years. At the age of five years she was taken to a specialized service: the patient was malnourished and with 9 cms palpable spleen and 2 cms liver. Laboratory investigation initiated at that time showed deficiency of IgG, IgA, IgM serum, absence of isohemaglutininas, and normal B, T, CD4+ and CD8+ lymphocytes. The liver biopsy revealed granulomatous disease. It was then diagnosed as granulomatous CVID. The patient was submitted to immunodeficiency treatment and steroid was indicated for the granulomatous disease. The patients monthly monitoring during 21 years showed good outcome, with regression of hepatosplenomegaly and preservation of liver function. Discussion: CVID is predominantly a primary deficiency of antibodies, in which there is recurrent pneumonias and the main treatment recommended is the replacement of gammaglobulin. The granulomatous form of CVID is rare, nevertheless it must be diagnosed early so that the liver function can be preserved. In this 21-year-monitoring case there has been a good evolution of the granulomatous form of immunodeficiency with low doses of steroids.
Assuntos
Humanos , Feminino , Anticorpos , Linfócitos B , Imunodeficiência de Variável Comum , Técnicas e Procedimentos Diagnósticos , Granuloma , Imunoglobulinas/deficiência , Relatos de Casos , Métodos , Pacientes , MétodosRESUMO
Kabuki syndrome is a genetic disorder of unknown etiology associated with characteristic features (long palpebral fissures, everted lower lids, and arched eyebrows), mental retardation, congenital malformations and increased susceptibility to infections, cancer and autoimmune diseases. However, few studies concerning the immunological aspects of the disease have been performed, and no clear cause of immunodeficiency has been established. Methods: Basic immunological evaluation of nine Brazilian children and adolescents with Kabuki syndrome was performed. Results: Clinical findings include recurrent respiratory infections (mainly otitis media and pneumonia) in 8 patients and allergic respiratory and/ or cutaneous diseases in 5 children. Laboratory findings include selective IgA deficiency, mildly decreased total IgG levels, decreased IgG2 and lack of an adequate response to delayed skin hypersensitivity testing. All of the patients seroconverted after vaccination with heptavalent conjugate pneumococcal vaccine. In two children, clinical and cytogenetic diagnosis of Turner syndrome was also established, while one of them also presented selective IgA deficiency. Conclusion: Due to these findings, we believe that further research is needed for a better understanding of the underlying causes of immunodeficiency in Kabuki syndrome...
A síndrome de Kabuki é uma condição genética de etiologia desconhecida caracterizada por retardo mental, baixa estatura, malformações congênitas, fáscies característico (fissuras palpebrais longas, eversão das pálpebras inferiores e supercílios arqueados) e uma susceptibilidade aumentada a infecções, doenças autoimunes e neoplasias. No entanto, há poucos estudos disponíveis sobre os aspectos imunológicos desta síndrome e até o momento não se estabeleceu causa para essa imunodeficiência. Método: Foi realizada uma avaliação imunológica básica de nove crianças e adolescentes brasileiros com síndrome de Kabuki. Resultados: Os achados clínicos incluíram infecções respiratórias recorrentes (principalmente otite média e pneumonia) em 8 dos pacientes e atopia (dermatite, rinite ou asma) em 5 crianças. Dentre os achados laboratoriais, pode-se citar deficiência seletiva de IgA, níveis reduzidos de IgG, redução de IgG2 e ausência de resposta aos testes cutâneos de hipersensibilidade tardia. Todos os pacientes soroconverteram após imunização com vacina pneumocócica conjugada heptavalente. Dois dos pacientes tiveram ainda o diagnóstico clínico e citogenético de síndrome de Turner, sendo que um deles também apresentava deficiência seletiva de IgA. Conclusão: Devido a estes achados, acreditamos que mais estudos devem ser realizados para que se tenha uma melhor compreensão das causas de imunodeficiência na síndrome de Kabuki...
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Anticorpos , Hipersensibilidade/imunologia , Síndromes de Imunodeficiência , Fatores Imunológicos , Imunocompetência/genética , Imunoglobulinas/deficiência , Adolescente , CriançaRESUMO
INTRODUCTION: Associations between systemic lupus erythematosus (SLE) and primary immunodeficiencies (PIDs) were analyzed to gain insight into the physiopathology of SLE. Some PIDs have been consistently associated with SLE or lupus-like manifestations: (a) homozygous deficiencies of the early components of the classical complement pathway in the following decreasing order: in C1q, 93% of affected patients developed SLE; in C4, 75%; in C1r/s, 57%; and in C2, up to 25%; (b) female carriers of X-linked chronic granulomatous disease allele; and (c) IgA deficiency, present in around 5% of juvenile SLE. DISCUSSION: In the first two groups, disturbances of cellular waste-disposal have been proposed as the main mechanisms of pathogenesis. On the other hand and very interestingly, there are PIDs systematically associated with several autoimmune manifestations in which SLE has not been described, such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX), and autoimmune lymphoproliferative syndrome (ALPS), suggesting that mechanisms considered as critical players for induction and maintenance of tolerance to autoantigens, such as (1) AIRE-mediated thymic negative selection of lymphocytes, (2) Foxp3+ regulatory T cell-mediated peripheral tolerance, and (3) deletion of auto-reactive lymphocytes by Fas-mediated apoptosis, could not be relevant in SLE physiopathology. The non-description of SLE and neither the most characteristic SLE clinical features among patients with agammaglobulinemia are also interesting observations, which reinforce the essential role of B lymphocytes and antibodies for SLE pathogenesis. CONCLUSION: Therefore, monogenic PIDs represent unique and not fully explored human models for unraveling components of the conundrum represented by the physiopathology of SLE, a prototypical polygenic disease.
Assuntos
Autoimunidade , Síndromes de Imunodeficiência/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Animais , Ligante de CD40/genética , Ligante de CD40/imunologia , Proteínas do Sistema Complemento/deficiência , Proteínas do Sistema Complemento/genética , Suscetibilidade a Doenças , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Humanos , Imunoglobulinas/deficiência , Imunoglobulinas/genética , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/fisiopatologia , Lúpus Eritematoso Sistêmico/etiologia , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/fisiopatologia , Camundongos , Polimorfismo Genético , Tolerância a Antígenos Próprios , Fatores de Transcrição/genética , Fatores de Transcrição/imunologia , Proteína AIREAssuntos
Autoimunidade , Síndromes de Imunodeficiência/imunologia , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/imunologia , Humanos , Imunidade Inata , Imunoglobulinas/deficiência , Imunoglobulinas/genética , Imunoglobulinas/imunologia , Síndromes de Imunodeficiência/genética , Lactente , Masculino , Polimorfismo Genético , Tolerância a Antígenos Próprios , Fatores de Transcrição/genética , Fatores de Transcrição/imunologia , Proteína AIRERESUMO
La ataxia-telangiectasia (AT) es una enfermedad autosómica recesiva caracterizada por ataxia cerebelosa progresiva, telangiectasias oculocutáneas, infecciones sinopulmonares recurrentes, inmunodeficiencia, e hipersensibilidad a las radiaciones ionizantes, con mayor susceptibilidad al desarrollo de tumores malignos linforreticulares. Presentamos un paciente de sexo masculino de 16 años, con diagnóstico de ataxia-telangiectasia desde los 3 años de vida, con las manifestaciones clínicas y los exámenes complementarios característicos de esta entidad. Se destaca la necesidad del seguimiento de estos pacientes por un grupo interdisciplinario debido al compromiso multisistémico de esta enfermedad.
Assuntos
Humanos , Masculino , Adolescente , Pele/patologia , Hospedeiro Imunocomprometido , Imunoglobulinas/deficiência , Infecções RespiratóriasAssuntos
Anticorpos Monoclonais/farmacologia , Antígenos CD19/efeitos dos fármacos , Imunoglobulinas/deficiência , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adolescente , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais Murinos , Pré-Escolar , Doença Crônica , Feminino , Humanos , Imunoglobulinas/efeitos dos fármacos , Masculino , RituximabRESUMO
OBJECTIVE: To characterize the immunodeficiency in ataxia-telangiectasia (A-T) and to determine whether the immunodeficiency is progressive and associated with increased susceptibility to infections. STUDY DESIGN: Records of 100 consecutive patients with A-T from the Johns Hopkins Ataxia-Telangiectasia Clinical Center (ATCC) were reviewed. RESULTS: Immunoglobulin (Ig) deficiencies are common, affecting IgG4 in 65% of patients, IgA in 63%, IgG2 in 48%, IgE in 23%, and IgG in 18%. Lymphopenia affected 71% of patients, with reduced B-lymphocyte number in 75%, CD4 T lymphocytes in 69%, and CD8 T lymphocytes in 51%. There was no trend for increased frequency or severity of immune abnormalities with age. Recurrent upper and lower respiratory tract infections were frequent: otitis media in 46% of patients, sinusitis in 27%, bronchitis in 19%, and pneumonia in 15%. Sepsis occurred in 5 patients, in 2 patients concurrent with cancer chemotherapy. Warts affected 17% of patients, herpes simplex 8%, molluscum contagiosum 5%, candidal esophagitis 3%, and herpes zoster 2%. Uncomplicated varicella infection occurred in 44% of patients; 2 patients had more than one clinical episode. No patient had Pneumocystis jerovici pneumonia or a complication of live viral vaccine. CONCLUSIONS: In spite of the high prevalence of laboratory immunologic abnormalities, systemic bacterial, severe viral, and opportunistic infections are uncommon in A-T. Cross-sectional analysis suggests that the immune defect is rarely progressive.
Assuntos
Ataxia Telangiectasia/complicações , Ataxia Telangiectasia/imunologia , Imunoglobulinas/deficiência , Infecções Respiratórias/imunologia , Adolescente , Adulto , Fatores Etários , Ataxia Telangiectasia/tratamento farmacológico , Ataxia Telangiectasia/mortalidade , Varicela/complicações , Varicela/imunologia , Criança , Pré-Escolar , Esofagite/complicações , Esofagite/imunologia , Esofagite/microbiologia , Feminino , Herpes Zoster/complicações , Herpes Zoster/imunologia , Humanos , Imunoglobulinas/sangue , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Células Matadoras Naturais/metabolismo , Leucopenia/imunologia , Contagem de Linfócitos , Linfopenia/imunologia , Masculino , Otite Média/complicações , Otite Média/imunologia , Infecções Respiratórias/complicações , Sepse/complicações , Sepse/imunologia , Dermatopatias Virais/complicações , Dermatopatias Virais/imunologiaRESUMO
OBJECTIVE: To determine the serum immunoglobulin concentrations in children with asthma and recurrent rinofaringitis. MATERIAL AND METHODS: We made a descriptive survey in children with persistent moderate asthma and with recurrent infections. Serum IgA, IgG, IgM and IgE concentrations was determined in the laboratory of Immunology and the results were considered according to the age and to the technique used in the laboratory. RESULTS: They were 45 patients (26 males and 19 females) with age average of 5.5 +/- 2.8 years +/- SD. In 12 patients (26%) had deficiency of IgA, in 2 (4%) it was absolute and in 10 (22%) it was partially. They were 4 (9%) with deficiency of IgG and IgM had not deficiency, but in 5 (11%) had elevated concentrations. We find 28 patients (62%) with high serum IgE. CONCLUSIONS: The prevalence of the serum immunodeficiency would be bigger if they were looked for deliberately in groups with risk, like it is demonstrated in this study, where, of the 45 patients they met 18 with some serum immunoglobulin deficiency (40%).