Asma alérgica e não alérgica apresentam diferentes características fenotípicas e genotípicas / Allergic and non-allergic asthma have different phenotypic and genotypic characteristics

Objetivo: A identificação dos fenótipos da asma permite uma melhor compreensão e abordagem desta doença heterogênea. Muitos estudos têm demonstrado associação entre os antígenos leucocitários humanos (HLA) e asma em diversas populações, porém os resultados são inconclusivos e raramente consideram uma doença com diferentes fenótipos. O objetivo deste estudo foi caracterizar os fenótipos alérgico e não alérgico da asma e avaliar possíveis associações com o sistema HLA. Métodos: Um total de 190 pacientes com asma foram prospectivamente acompanhados durante dois anos. Foram divididos em dois grupos, asma alérgica e não alérgica, de acordo com a história clínica e os resultados do teste cutâneo de puntura e da pesquisa da IgE sérica específica. O grupo controle foi composto por 297 doadores falecidos de órgãos sólidos. As características de cada grupo e a tipificação dos HLA classe I e II foram avaliadas e comparadas. Resultados: O estudo mostrou diferentes características entre os fenótipos estudados. Os pacientes com asma não alérgica relataram uma idade mais tardia de início dos sintomas da doença e maior frequência de história sugestiva de intolerância aos anti-inflamatórios não esteroidais. O grupo asma alérgica apresentaram IgE sérica total elevada, presença de dermatite atópica e rinoconjuntivite mais frequente e, inesperadamente, maior gravidade da doença. Novas associações entre os genótipos HLA e os fenótipos alérgico e não alérgico da asma foram identificados. Os genótipos HLA-B*42, HLA-C*17, HLA-DPA1*03 e HLA-DPB1*105 foram associados com a asma alérgica, e o HLA-B*48 com o fenótipo não alérgico. A presença do haplótipo HLA-DPA1*03 DQA*05 foi associado com asma alérgica, e a presença do HLA-DPA1*03 e ausência do HLA-DQA*05 com a asma não alérgica. Conclusões: A asma alérgica e não alérgica apresentaram diferentes características fenotípicas e genotípicas. Novas associações entre os fenótipos e o sistema HLA classe I e II foram identificadas.

Objective: The identification of asthma phenotypes allows a better understanding and management of this heterogeneous disease. Studies have reported associations between human leukocyte antigens (HLA) and asthma in different populations, but results have been inconclusive and rarely take into consideration the distinct disease phenotypes. The objectives of this study were to characterize allergic and non-allergic asthma phenotypes and to evaluate possible associations with the HLA system. Methods: A total of 190 patients with asthma were prospectively followed during two years. They were divided into two groups, allergic and non-allergic asthma, according to clinical history and the results of skin prick testing and serum-specific IgE measurement. The control group comprised 297 deceased donors of solid organs. The characteristics of each group and HLA class I and II genotypes were assessed and compared. Results: The study revealed different characteristics between the phenotypes studied. Nonallergic patients were older at the onset of asthma symptoms and had a higher rate of history of intolerance to non-steroidal antiinflammatory drugs. Allergic patients showed higher total serum IgE levels, reported atopic dermatitis and rhinoconjunctivitis more frequently, and, unexpectedly, showed greater disease severity. New associations between HLA genotypes and the allergic/non-allergic asthma phenotypes were identified. HLA-B*42, HLA-C*17, HLADPA1* 03, and HLA-DPB1*105 genotypes were associated with allergic asthma, and HLA-B*48, with the non-allergic phenotype. The presence of haplotype HLA-DPA1*03 DQA*05 was associated with allergic asthma, and the presence of HLA-DPA1*03 and absence of HLA-DQA*05, with non-allergic asthma. Conclusion: Allergic and non-allergic asthma have distinct phenotypic and genotypic characteristics. New associations between asthma phenotypes and HLA class I and II were identified.

Acute disseminated encephalomyelitis: clinical features, HLA DRB1*1501, HLA DRB1*1503, HLA DQA1*0102, HLA DQB1*0602, and HLA DPA1*0301 allelic association study / Encefalomielite aguda disseminada: características clínicas e estudo de associação com os alelos HLA DRB1*1501, HLA DRB1*1503, HLA DQA1*0102, HLA DQB1*0602 e DPA1*0301

We evaluated the frequency, demographic, clinical, disability evolution and genetic association of HLA DRB1*1501, DRB1*1503, DQA1*0102, DQB1*0602 and DPA1*0301 alleles in patients diagnosed as acute disseminated encephalomyelitis (ADEM) among a population of CNS demyelinating diseases. Fifteen patients (8.4 percent) of our series were diagnosed as ADEM. The mean age onset was 35.23 years (range 12 to 77), 53.3 percent were male and follow-up range was 8.5 to 16 years. Two cases (13.3 percent) had a preceding infection before neurological symptoms, one presented a parainfectious demyelinating, and one case had been submitted to hepatitis B vaccination four weeks before the clinical onset. The EDSS range was 3.0 to 9.5. Eight patients (53.3 percent) presented MRI with multiple large lesions. CSF was normal in 73.3 percent. The severe disability observed at EDSS onset improved in 86.66 percent patients. The genetic susceptibility for ADEM was significantly associated with the HLA DQB1*0602, DRB1*1501 and DRB1*1503 alleles (<0.05) in monophasic ADEM.

Avaliamos as frequencia, características demográficas, clínicas e de associação genética dos alelos HLA DRB1*1501, DRB1*1503, DQA1*0102, DQB1*0602 e DPA1*0301 em pacientes com diagnóstico de encefalomielite aguda disseminada (ADEM) em população com doença desmielinizante do SNC. Quinze (8,4 por cento) pacientes de nossa série foram diagnosticados como ADEM. A média de idade foi 35,23 anos (variando entre 12 e 77), 53,3 por cento eram homens e o tempo de acompanhamento variou entre 8,5 e 16 anos. Dois casos (13,3 por cento) apresentaram infecção prévia, um apresentou processo desmielinizante para infeccioso e outro havia se submetido a vacinação para hepatite B quatro semanas antes. O EDSS variou entre 3,0 e 9,5. Oito pacientes (53,3 por cento) apresentaram grandes lesões na RM. O LCR foi normal em 73,3 por cento. A incapacidade grave quantificada pelo EDSS foi seguida de melhora importante em 86,6 por cento dos pacientes. A susceptibilidade genética na ADEM foi significativamente associada com os alelos HLA DQB1*0602, DRB1*1501 e DRB1*1503 (p<0,05) nos pacientes com quadro monofásico.

HLA y diabetes mellitus insulino-dependiente / HLA and insulin-dependent diabetes mellitus

The propensity of an individual to develop type I (insulin dependent) diabetes mellitus is directly related to specipic HLA clase II proteins, specially those from DR and DQ regions. Genetic susceptibility to insulin dependent diabetes arises from a preestablished conformation of alpha and ß chains of DQ and ß chain of DR. Since the classic demonstration by McDevitt and colleagues that DQ ß chain aspartate at position 57 was protective against the development of the disease, many populations have been surveyed to study the association between the incidence Type I diabetes and determined frequencies of DR and DQ haplotypes. The assocation between these markers and susceptibility to Type I diabetes is well established in caucasians at the present time. However, little information is available for Latin American populations, that share a mixture of european, african and native genes. Our group is studying genetic markers of three Latin American populations (Argentina, Perú and Chile) and their possible association to the different incidence of Type I diabetes mellitus in each country

Immunopathology of american cutaneous leishmaniasis. Modulation of MHC class II gene products by Keratinocytes before and after glucantime therapy

Epidermal changes from 32 cutaneous and 3 mucosal American leishmaniasis (ACL) active lesions were studied for HLA-DR, -DP expression, Lanerhans cells and lymphocyte infiltration. In addition to a DR and DQ positivity at the surface of the cells of the inflammatory infiltrate, a strong reaction for DR antigens was detected on keratinocytes. Hyperplasia of Langerhans cells was present in al cutaneous lesions and epidermis was infiltrated by T lymphocytes. When healed lesions of 14 of these subjects were re-biopsied 1 to 12 months after the end of pentavalent antimonial therapy, MHC class antigens could no longer be seen on keratinocytes. Our data represrn evidence for hhe reversibility of the abnormal HLA-DR expression by keratinocytes in ACL after Glucantime therapy or spontaneous scar formation, demonstrating that this expresion is restricted to the period of active lesions. The present findings can be regarded as an indirect evidence that keratinocytes may be involved in the immunopathology of ACL

DNA analysis of histocompatibility antigens: identification of new DQw specificities and of DPw patterns

The HLA-D region of the major histocompatibility complex has several subregions, the most important of which are DR, DQ and DP. The genes coding for the beta chains of these proteins present most of the polymorphisms which result in the large variety of class II antigens observed. We have studied the restriction fragment length polymorphism (RFLP) of the DQ beta and DP beta genes in order to establish accurate typing patterns. The data show that DQ typing based on RFLP permits the identification of the recently described DQw1 splits (new antigenic specificities), DQw5 and DQw6. The TA 10-monoclonal antibody-positive split of DQw3, designated DQw7, is associated with specific DNA fragments after digestion with four different enzymes: Taq I, Hind III, Pvu II and Bg1 II. Furthermore, the recently reported specificity DQw4 (formerly typed as a blank) is associated with a specific 2.4-kb fragment when the DNA is digested with EcoRV. DP typing proved to be more difficult even though six enzymes were used, and only broad groups could be identified