Molecular analysis of human leukocyte antigen class I and class II allele frequencies and haplotype distribution in Pakistani population.

AIM: Distribution of HLA class I and II alleles and haplotype was studied in Pakistani population and compared with the data reported for Caucasoid, Africans, Orientals and Arab populations. MATERIALS AND METHODS: HLA class I and II polymorphisms in 1000 unrelated Pakistani individuals was studied using sequence-specific primers and polymerase chain reaction and assay. RESULTS: The most frequent class I alleles observed were A*02, B*35 and CW*07, with frequencies of 19.2, 13.7 and 20%, respectively. Fifteen distinct HLA-DRB1 alleles and eight HLA-DQB1 alleles were recognized. The most frequently observed DRB1 alleles which represented more than 60% of the subjects were DRB1 *03, *07, *11 and *15. The rare DRB1 alleles detected in this study were HLADRB1 *08 and *09, having frequencies of 0.9 and 1.7%, respectively. In addition, at DRB1-DQB1 loci there were 179 different haplotypes and 285 unique genotypes and the most common haplotype was DRB1*15-DQB1*06 which represented 17% of the total DRB1-DQB1 haplotypes. In our population, haplotype A*33-B*58-Cw*03 comprised 2.8% of the total class I haplotypes observed. This haplotype was seen only in the oriental populations and has not been reported in the African or European Caucasoid. CONCLUSION: Our study showed a close similarity of HLA class I and II alleles with that of European Caucasoid and Orientals. In Pakistani population, two rare loci and three haplotypes were identified, whereas haplotypes characteristic of Caucasians, Africans and Orientals were also found, suggesting an admixture of different races due to migration to and from this region.

Preliminary study of HLA-ABCDR antigens in CML, ANLL, thalassemia and severe aplastic anemia in Thais.

The objective of this study was to analyse human leukocyte antigen (HLA) and disease association in common blood diseases [chronic myelogenous leukemia (CML), acute nonlymphocytic leukemia (ANLL), thalassemia and severe aplastic anemia] in Thais. The subjects were patients from the Hematological Clinic, Departments of Medicine and Pediatrics, Ramathibodi Hospital who were referred for HLA typing for bone marrow transplantation (BMT) at the Histocompatibility Laboratory from March 1988 to September 1997. A total of 129 patients had complete HLA-ABC typing. The patients included 45 CML, 40 ANLL, 26 thalassemia (Thal) and 18 severe aplastic anemia (SAA). Of these, 88 patients were typed for HLA class II. The HLA class I (ABC) and II (DR, DQ) typings were performed by microlymphocytotoxicity test. It was found that HLA class I was associated with CML, ANLL and Thal, whereas, HLA class II was associated with SAA. HLA-B8 and HLA-B18 were increased in CML with R.R. values of 12.2 and 3.9, respectively, whereas, HLA-B18 was increased in ANLL with R.R. value of 4.5. In addition, HLA-DR2 and DR3 were increased in SAA with R.R. values of 3.8 and 4.8, respectively. For Thal, HLA-A2 and B46 were increased in Thal in Central Thais with R.R. values of 3.3 and 6.1, respectively, whereas, HLA-B13 was increased in Thal in Northern Thais with R.R. value of 8.5. On the other hand, HLA-B7 was absent in CML. HLA-Cw7 was decreased in CML and SAA, whereas, HLA-DR6 was decreased in ANLL and SAA. Furthermore, HLA-Cw6 was also decreased in CML, whereas, HLA-A33 and Bw4 were decreased in SAA. Although the sample size of each disease was small, the increase of HLA-DR2 was observed in SAA in Thais which was similar to other studies in different ethnic groups. These preliminary data may be useful for further study in HLA and blood disease association.

Human leucocytic antigens (HLA) in breast cancer.

HLA frequencies of fifty (50) female breast cancer patients were compared with 200 age matched female controls. A total of 20 HLA-A locus, 35 HLA-B locus and 8 HLA-C locus antigens were studied. The HLA-A2, A11, Aw19 and A30; HLA-B8, B14 and HLA Cw6 were found significantly higher than the controls. The HLA-A11, HLA-Aw19 and HLA-B8 were found protective whereas, HLA-A2, HLA-B14 and HLA-Cw6 were a risk for breast cancer. The prective antigens' probable involvement through immunogenic mechanism in breast cancer is emphasized in this article.

HLA association with sarcoidosis and diffuse interstitial pulmonary fibrosis.

HLA typing was performed on 18 patients suffering from sarcoidosis and 30 patients suffering from diffuse interstitial pulmonary fibrosis. One hundred normal healthy people ethnically matched served as the controls. On statistical analysis, the corrected 'p' value of all the HLA antigens for both the patient groups was non significant. The results therefore suggest that there is no particular HLA antigen associated with sarcoidosis and diffuse interstitial pulmonary fibrosis.

Análise de associação entre cardiopatia chagásica crônica e antígenos HLA de classe I (HLA-A, -B e -C) e de classe II (HLA-DR e -DQ) / Analysis of association between chronic Chagas Cardiomyopathy and antigens HLA of class I (HLA It, - B and - C) and of class II (HLA-DR and - DQ)

Considerando que o sistema HLA contem genes que controlam a resposta imune, bem como genes de susceptibilidade genética a diversas doenças, temos como objetivo a realização de um estudo de associação entre os antígenos HLA e a doença de CHAGAS, forma cardíaca. Foram analisadas as freqüências dos antigenos HLA-A, -B, -C, -DR E -DQ em 47 pacientes com cardiopatia chagásica crônica e 95 indivíduos controles. Essas amostras iniciais são constituídas por caucasóides e negroides. As analises estatísticas mostram um aumento estatisticamente significante da freqüência de HLA-DR2 nos pacientes, quando comparados com os controles. a significativo ns freqüências de dr-2, cujas freqüências nos pacientes e controles são de 48,3por cento e 12,3por cento, respectivamente (pc=0,0058). Os resultados sugerem uma associação positiva do antígeno DR-2 com cardiopatia chagásica crônica. Embora os resultados indiquem uma possível associação com DR-2 também em negroides, os nossos dados não são conclusivos para esse grupo racial, devido ao pequeno tamanho da amostra analisada

Lack of association between paracoccidioidomycosis and HLA histocompatibility antigens

Foi realizado um estudo de associaçäo HLA e doença, onde 40 pacientes com diagnóstico clínico e laboratorial de Paracoccidioidomicose (PCM) e, 80 indivíduos brancos, clinicamente saudáveis, usados como controles, foram tipados para os antígenos HLA-A, -B, -Cw, -DR e - DQ. Os resultados obtidos mostraram uma associaçäo positiva dos antígenos HLA-A1 (P = 0.050), -A3 (P = 0.014), -B8 (P = 0.014), -Cw7 (P = 0.020), - DQw2 (P = 0.014) e DQw3 (P = 0.019) nos pacientes e uma associaçäo negativa dos antígenos HLA-Cw3 (P = 0.032), -DR1 (P = 0.019) e -DQw1 (P = 0.003) no mesmo grupo, comparados aos controles e, sem correçäo pelo número de antígenos testados (50). Os resultados sugerem uma fraca associaçäo destes antígenos HLA com a doença, uma vez que outros fatores podem também estar influenciando na susceptibilidade genética à PCM. Se corrigido o valor de P, segundo Svejgaard e Ryder (HLA and disease, J, Dausset and A. Svejgaard, eds., 1977), nenhuma associaçäo é demonstrada neste estudo