Hypogammaglobulinemia: a diagnosis that must not be overlooked

Humoral immunological defects are frequent and important causes of hypogammaglobulinemia, leading to recurrent infections, autoimmunity, allergies, and neoplasias. Usually, its onset occurs in childhood or during the second and third decades of life; however, the diagnosis is made, on average, 6 to 7 years afterwards. As a consequence, antibody defects can lead to sequelae. Here we describe the clinical-laboratory characteristics, treatment, and prognoses of patients with hypogammaglobulinemia. An observational, cross-sectional, and retrospective study of patients attending the recently established outpatient group of Clinical Immunology between 2013 and 2018 was carried out. Patients with IgG levels below 2 standard deviations from the mean values for the age and/or impaired antibody response were included. Eight patients (3 F and 5 M; median age=41 years (16-65), average symptom onset at 25 years (1-59), and time to diagnosis of 10 years were included. The main infections were: sinusitis in 7/8, pneumonia in 6/8, otitis in 2/8, tonsillitis and diarrhea in 2/8, and diarrhea in 2/8 patients. Hypothyroidism was identified in 4/8 (50%) patients. Rhinitis was found in 7/8 (87.5%) and asthma in 3/8 (37.5%) patients. The tomographic findings were consolidations, atelectasis, emphysema, ground glass opacity, budding tree, bronchial thickening, and bronchiectasis. Immunoglobulin reposition was used between 466 and 600 mg/kg monthly (514.3 mg·kg-1·dose-1). Prophylactic antibiotic therapy was included in 7/8 (87.5%) patients. Airway manifestations prevailed in patients with hypogammaglobulinemia. There is a need for educational work to reduce the time of diagnosis and initiation of treatment, avoiding sequelae.

Hereditary angioedema with C1 inhibitor (C1-INH) deficit: the strength of recognition (51 cases)

Hereditary angioedema (HAE) is a rare autosomal dominant disease due to C1 esterase inhibitor deficiency (C1-INH). The disease is characterized by subcutaneous and submucosal edema in the absence of urticaria due to the accumulation of bradykinin. This descriptive study aimed to evaluate the clinical characteristics of patients with a confirmed diagnosis of HAE referred to our Outpatient Clinic between December 2009 and November 2017. Fifty-one patients (38 F, 13 M) with a mean age of 32 years (range: 7-70 y) were included. Family history of HAE was reported in 70% (36/51) of the cases; 33/46 patients became symptomatic by 18 years of age. The median time between onset of symptoms and diagnosis was 13 years (3 mo-50 y). The most frequent triggering factors for attacks were stress (74.4%), trauma (56.4%), and hormonal variations (56%). The main symptoms were subcutaneous edema in 93.5% (43/46) of patients, gastrointestinal symptoms in 84.8% (39/46), and obstruction in the upper airways in 34.8% (16/46). Hospitalization occurred in 65.2%, of whom 13.3% had to be transferred to the Intensive Care Unit. Prophylactic treatment was instituted in 87% (40/46) of patients, and 56.5% (26/46) required additional treatment to control attacks. Owing to our data collection over a period of 8 years, a significant number of patients were identified by this HAE reference center. Despite early recognition and prophylactic treatment, a high percentage of patients were hospitalized. HAE is still diagnosed late, reinforcing the need for more reference centers specialized in diagnosis and educational projects for health professionals.

The use of reverse transcription-PCR for the diagnosis of X-linked chronic granulomatous disease

Chronic granulomatous disease (CGD) is an inherited disorder of the innate immune system characterized by a defective oxidative burst of phagocytes and subsequent impairment of their microbicidal activity. Mutations in one of the NADPH-oxidase components affect gene expression or function of this system, leading to the phenotype of CGD. Defects in gp91-phox lead to X-linked CGD, responsible for approximately 70 percent of CGD cases. Investigation of the highly heterogeneous genotype of CGD patients includes mutation analysis, Northern blot or Western blot assays according to the particular case. The aim of the present study was to use reverse transcription (RT)-PCR for the analysis of molecular defects responsible for X-linked CGD in eight Brazilian patients and to assess its potential for broader application to molecular screening in CGD. Total RNA was prepared from Epstein B virus-transformed B-lymphocytes and reverse transcribed using random hexamers. The resulting cDNA was PCR-amplified by specific and overlapping pairs of primers designed to amplify three regions of the gp91-phox gene: exons 1-5, 3-9, and 7-13. This strategy detected defective gp91-phox expression in seven patients. The RT-PCR results matched clinical history, biochemical data (nitroblue tetrazolium or superoxide release assay) and available mutation analysis in four cases. In three additional cases, RT-PCR results matched clinical history and biochemical data. In another case, RT-PCR was normal despite a clinical history compatible with CGD and defective respiratory burst. We conclude that this new application of RT-PCR analysis - a simple, economical and rapid method - was appropriate for screening molecular defects in 7 of 8 X-linked CGD patients.

Avaliaçäo do sistema complemento em crianças, em diversos estádios da infecçäo pelo HIV: correlaçäo clínico-laboratorial / Evaluation of complement system in children in different phases of HIV infection: clinical and laboratorial correlation

Objetivo: A ativaçäo do complemento foi demonstrada em pacientes adultos infectados pelo HIV, no entanto, poucas informaçöes estäo disponíveis em crianças infectadas no período perinatal. O objetivo do presente estudo foi analisar a funçäo do sistema complemento em crianças infectads pelo HIV. Método: 127 crianças infectads pelo HIV no período neonatal (onze a 134 meses, 62 do sexo masculino: 65 do sexo feminino) foram incluídas e classificadas de acordo com os critérios clínicos e imunológicos do Centro de Controle de Doenças (Atlanta, EUA), de 1994. O diagnóstico da ativaçäo do sistema complemento foi realizado pelos seguintes ensaios: CH50 para via clássica, APH50 para via alternativa (APH50), ELISA para via das lectinas (MBL) e 'rocket' imunoeletroforese para o produto de C3,C3dg/C3d. Resultados: As infecçöes mais freqüentes foram: pneumonia bacteriana, otite, diarréia e infecçöes oportunistas como pneumonia por Pneumocystis carinii e tuberculose (31,5 por cento). A miocardiopatia foi a única apresentaçäo clínica que se relacionou com o estado imunológico (categoria 3). Nenhuma diferença estatisticamente significante nas funçöes da via clássica e alternativa foi observada entre os pacientes das diferentes categorias. Valores médios aumentados de CH50, APH50 e MBL foram verificados em pacientes nos estádios mais avançados da doença. Níveis elevados de C3d na maioria dos pacientes indicam que o complemento encontra-se ativado durante a infecçäo pelo HIV em crianças. CH50, APH50, e MBL estavam abaixo dos limites inferiores em duas, dez e duas crianças, respectivamente.

Deficiência de IgA: avaliaçäo clínico-laboratorial de 60 pacientes do Instituto da Criança / IgA deficiency: clinical and laboratorial evaluation of 60 patients from \"Instituto da Criança\"

Objetivos. Caracterizar os principais dados clínicos que orientem a pesquisa da DIgA e descrever sua evoluçao clínica e complicaçoes durante o seguimento ambulatorial. Material e Métodos. Foram avaliados, retrospectivamente, 60 pacientes portadores de DIgA (níveis séricos de IgA < 5 mg/dL) e submetidos à avaliaçao Clínica e provas laboratoriais específicas. Resultados. As queixas principais foram os processos infecciosos (50 por cento), quadros alérgicos (34 por cento) e doenças auto-imunes (10 por cento). Os processos infecciosos recorrentes acometeram preferencialmente o trato respiratório, sendo asma e rinite as manifestaçoes alérgicas mais frequentes. à avaliaçao laboratorial, além da deficiência de IgA, apenas os níveis de IgG e IgM encontravam-se elevados em 50 por cento dos pacientes. Durante a evoluçao, houve melhora da sintomatologia clínica e alguns pacientes tornaram-se assintomáticos durante a idade escolar e puberdade. Conclusao: A DIgA tem espectro clínico variado devendo ser sempre pesquisada em pacientes com infecçoes de repetiçao, processos alérgicos ou doenças auto-imunes para orientaçao de profilaxia precoce dos processos infecciosos e doenças alérgicas.

An alternative method for in vitro production of HIV-1-specific antibodies

We describe the detection of HIV-1-specific antibody secretion by a 24-h culture of peripheral blood mononuclear cells (PBMC) stimulated with disrupted inactivated whole virus absorved onto commercial ELISA microwell plates. The method showed high sensitivity and specificity and was capable of accurately detecting HIV-1 infection early after birth (9 of the 19 patients were < 3 years old) because maternal antibodies do not iterfere by giving false-postive results. No false-positive results were obtained with PBMC from 24 HIV-1-seronegative asymptomatic individuals and no false-negative results were obteined for 10 seropostive adult patients (16-46 years pf age). This rapid, relatively low cost, simple, highly sensitive and specific assay can be extremely useful for the early diagnosis of pediatric AIDS cases

Primary immunodeficiency diseases: a presentation of 6 cases

The peripheral blood leukocytes of 6 children with clinical data suggestive of primary cellular immunodeficiencies were studied in an attempt the cellular basis of these disorders. The phenotype and function of T and B cells were investigated. According to the clinical and laboratory fetures, the patients were classified as one case of severe combined immunodeficiency (SCID), two of ataxia-telangiectasia (AT), one of Wiskott-Aldrich syndrome (WAAS), one of /edi%george syndrome (DSG), and one of cellular immunodeficiency (CID). The laboratory investigations together with the clinical manifestations permitted a diagnosis of primary immunodeficiency diseases

Aplasia medular prolongada como manifestacao pre-leucemica. / Long-term medullary aplasia as pre-leucemic manifestation

Os autores apresentam um caso de aplasia medular prolongada, em crianca de 7 anos e 8 meses de idade, medicado com androgeno por 9 meses sem melhoria do quadro hematologico, ate que foram constatados 32% de celulas leucemicas ao hemograma o que permitiu, entao, o diagnostico de leucemia mielomonocitica, tendo sido possivel obter remissao completa. Os autores comentam a importancia da identificacao de estados pre-leucemicos