HLA-B*5701 frequency in Chilean HIV-infected patients and in general population

It has been demonstrated that HLA-B*5701 screening reduces the risk for hypersensitivity reaction to abacavir in HIV-infected patients. Since B*5701 prevalence varies among different populations, it is important to determine the carrier frequency prior to its use for the screening of HIV-infected patients.The aim of this study was to determine HLA-B*5701 carrier frequency in Chilean general population and HIV-infected patients referred for B*5701 typing. For that purpose 300 blood bank donors and 492 abacavir-naïve HIV-infected patients from Chile were screened for B*5701 by a sequence specific primer PCR.We detected 14/300 (4.7 percent) B*57-positive individuals in the Chilean general population, 11 (3.7 percent) were B*5701 positive, and 3 (1 percent) had another subtype.All were heterozygous,thus a B*5701 allele frequency of 2 percent was determined.Eleven of 492 (2.2 percent) HIV-patients carried a B*5701 allele. The difference between these frequencies is probably due to slow progression of HIV infection in HLA-B*5701 carriers, thus less patients would require antiretroviral therapy and B*5701 typing. Considering the usefulness of B*5701 screening, its prevalence in the Chilean general population,and the availability of a validated method,we conclude that HLA-B*5701 typing in Chilean HIV-infected patients about to initiate abacavir treatment is strongly recommended.

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.

Associação entre HLA e leucemia em uma população brasileira de etnia mista / Association between HLA and leukemia in a mixed Brazilian population

OBJETIVOS: O objetivo deste estudo foi investigar a freqüência de antígenos HLA Classe I e de alelos HLA Classe II em 164 pacientes com vários tipos de leucemias: 35 pacientes com LLA (leucemia linfóide aguda), 50 com LMA (leucemia mielóide aguda) e 78 com LMC (leucemia mielóide crônica). MÉTODOS: A tipagem HLA Classe I foi realizada por microlinfocitotoxicidade e a de Classe II por PCR-SSP (polymerase chain reaction - sequence specific of primers), ambas da One Lambda (Canoga Park, CA, US). RESULTADOS: Em pacientes com LLA, as freqüências das variantes HLA-B45 e HLA-B56 foram maiores (P = 0,02; OR = 3,13; 95 por centoIC = 0,94-10,44; P = 0,03; OR = 3,61; 95 por centoIC = 0,47-27,64, respectivamente), quando comparadas com controles. Nos pacientes com LMA, a freqüência de HLA-B7 (P = 0,01; OR = 2,41; 95 por centoIC = 1,25-4,67) foi maior que em controles. A presença de HLA-B45 (P= 0,01; OR = 3,29; 95 por centoIC = 1,46-7,40) e de HLA-DRB1*04 (P = 0,002; OR = 2,17; 95 por centoIC = 1,36-3,46) e HLA-DRB1*08 (P = 0,004; OR = 2,36; 95 por centoIC = 1,34-4,16) foi associada ao maior risco de desenvolver LMC. CONCLUSÃO: Nossos resultados sugerem que variantes HLA conferem susceptibilidade a algumas formas de leucemia e podem prover novas ferramentas para a investigação da genética e etiologia desta doença.

OBJECTIVE: The main purpose of this study was to investigate the class I HLA antigens and class II HLA allele frequencies in 164 patients with leukemia: 35 patients with ALL (acute lymphoid leukemia), 50 with AML (acute myeloid leukemia) and 78 with CML (chronic myeloid leukemia). METHODS: The genotyping of class I HLA was performed by microlymphocytotoxicity and of class II by PCR-SSP (polymerase chain reaction - sequence specific of primers) (One Lambda, Canoga Park, CA, USA). RESULTS: In patients with LLA, frequencies of HLA-B45 and HLA-B56 were higher (P = 0.02; OR = 3.13; 95 percentIC = 0.94-10.44; P = 0.03; OR = 3.61; 95 percentIC = 0.47-27.64, respectively), than in controls. In patients with AML, the frequency of HLA-B7 (P = 0.01; OR = 2.41; 95 percentIC = 1.25-4.67) was higher than in controls. The presence of HLA-B45 (P= 0.01; OR = 3.29; 95 percentIC = 1.46-7.40), HLA-DRB1*04 (P = 0.002; OR = 2.17; 95 percentIC = 1.36-3.46) and HLA-DRB1*08 (P = 0.004; OR = 2.36; 95 percentIC = 1.34-4.16) was associated to increased risk of CML developing. CONCLUSION: Our results suggest that variants of HLA confer susceptibility to the same forms of leukemia, and could provide new tools for the investigation of genetics and etiology of this disease.

The Comparison Between Behcet's Disease and Spondyloarthritides: Does Behcet's Disease Belong to the Spondyloarthropathy Complex?

This study was to clarify whether Behcet's disease (BD) could be classified into the spondyloarthropathy (SpA) complex. It was undertaken on 58 patients with BD (BD group), 56 patients with SpA (SpA group), and 3 patients who concurrently satisfied the criteria for BD and SpA (BDSpA group). The clinical parameters and known susceptible HLA antigens were compared between BD group and SpA group. In addition, 3 patients in BDSpA group were reviewed. The prevalence of definitive sacroiliitis (SI) in BD group and SpA group was 46.4% and 5.2%, respectively. However, none had a definitive SI in healthy controls. Enthesitis was observed in 3.4% of BD group and in 50% of SpA group. The patterns of eye involvement were different between these two groups. HLA-B27 was negative in all 49 patients of BD group, whereas it was positive in 67.9% of SpA group. The prevalence of HLA-B51 was 51.7% in BD group, and that in SpA group was 21.4%. One patient in BDSpA group was considered to have concurrent BD and ankylosing spondylitis (AS). Another patient was closer to AS, and the third to BD. Conclusively, it seems that BD could not be classified into the SpA complex.

Alterations of HLA class I and II antigen expression in preinvasive, invasive and metastatic cervical cancers

HLA expression is altered in a large variety of human cancers. We performed immunohistochemical staining on tissues from normal, preinvasive, invasive and metastatic cervical cancer tissues using anti-HLA class I or class II antibody. In tissues from normal squamous epithelium, carcinoma in situ (CIS) and microinvasive carcinoma (MIC), the expressions of HLA-B, C heavy chains and class II heavy chain were significantly decreased as disease progressed. When the expression patterns were compared between primary and metastatic squamous cell carcinoma (SCC) lesions, statistically significant down-regulation of HLA class I and class II antigen in metastatic lesions was observed. The rates of HLA-B, C heavy chains and class II heavy chain expressions were all significantly down-regulated compared to the down-regulation rate of class I beta2-microglobulin (beta2m) in invasive squamous lesions, and the expressions of class II heavy chain in metastatic lesions was decreased further than that in primary lesions. Unlike SCC, the degree of HLA class I and class II loss was not evident as disease progressed in early stage of adenocarcinoma. In invasive adenocarcinoma lesions, only the expression of HLA-B, C heavy chains was decreased and no differences were seen in HLA-B, C heavy chain expression patterns between primary and metastatic lesions. These results suggest that alterations of HLA class I and II expressions seem to occur at a particular step in cervical cancer development and depend on tissue types: when the tumor becomes invasive and starts to metastasize.

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.

Distribution of HLA-A and B antigens in northeastern-Thais.

The phenotype and gene frequencies of HLA class I were studied in the Northeastern Thai population. Blood samples were collected from 100 unrelated healthy Northeastern Thais. HLA-A and B antigens were typed by using the standard microlymphocytotoxicity test. Twelve HLA-A and twenty-five HLA-B antigens were found in this population. HLA-A2, A24, A11 and the HLA-B46, B15, B22 antigens are commonly found in this group. Linkage disequilibrium analysis indicated the existence of fifteen haplotypes. The HLA-A2, B46 haplotype was the most common. These results will be useful for further studies in anthropology, organ transplantation and MHC associated disease in Northeastern Thais.

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

Quantitation of HLA antigens on red cells by immunoradiometric assay.

Immunoradiometric assay was employed to quantitate HLA antigens on red cells. Using this technique HLA-B7, HLA-B17 and HLA-A28 were detected on the red cells of all individuals studied irrespective of the serological status of the Bennett-Goodspeed (Bg) antigens. However, HLA antigenic sites for serologically Bg positive red cells were significantly more than that for Bg negative red cells (P less than 0.001). Bga positive red cells possessed maximum number of antigenic sites as compared to Bgb and Bgc positive red cells.

Human leucocyte antigen and insulin dependent diabetes mellitus.

HLA typing was done in 25 cases of insulin dependent diabetes mellitus (IDDM) and compared with 60 healthy controls. There was a significantly increased frequency of HLA B-8, HLA B-12 and HLA DR-3 in IDDMO. The odds ratio (relative risk) of developing IDDM for HLA B-8 was 4.42 (p less than 0.10), for HLA B-12 was 3.56 (p less than 0.10) and for HLA DR3 9.75 (p less than 0.001). There was no correlation of HLA specificity with complications of diabetes.

On the association between HLA-A1 and B5 and clinical forms of schistosomiasis mansoni

The association between both HLA-A1 and B5 antigens and chronic forms of human schistosomiasis was studied in 64 patients and 26 normal controls from a southern Brazilian hospital. No apparent correlation between the chronic forms of the disease and the expression of those antigens was detected. However, the analysis of these date together with those observed on an Egyptian sample suggests that the presence of either of the antigens and the hepatomegalic forms of schistosomiasis is significant, without heterogeneity. Converseley, the association of histocompatibility antigens with splenogegaly is consistent and significant only for HLA-B5, but not HLA-A1

HLA-B5 and B21 antigens in aortoarteritis.

The distribution of class I HLA antigens (HLA-A, B) were determined in 50 patients of Aortoarteritis in an Indian population. This included 29 females and 21 males. The difference in antigen frequency was observed between patients and controls with reference to HLA-A19, B5 and B21 antigens. A decreased frequency of HLA-A19 was observed in the patients as compared to controls (14% vs 33.25%, X2 = 6.81, P less than 0.025). Of the B locus antigens, an increased frequency of HLA B5 was observed in the patients as compared to controls (48% vs 29.5%, X2 = 6.2, P less than 0.025). HLA-B21 was also increased in the patients as compared to the controls (18% vs 6.5%, X2 = 6.67, P less than 0.025). These data suggest the involvement of genetic factor (s) in the aetiopathogenesis of this disease. Further, the observations indicate that HLA-B5 and B21 may be associated with Aortoarteritis.

HLA antigen and ventilatory drive in Thais with chronic obstructive pulmonary disease.

Studies of HLA antigens in 15 Thai patients with chronic obstructive pulmonary disease revealed a significant increase in HLA-Bw 60 frequency in the group with low ventilatory drive to carbondioxide using unstimulated airway pressure. The finding suggests an immunogenetic role of HLA-Bw 60 on the control of ventilation in COPD.

Spectrum of seronegative spondarthritides (SSA) with special reference to HLA profiles.

The present study describes the profile of seronegative spondarthritides (SSA) in young servicemen. SSA was diagnosed in 63 patients from a prospective study on spondyloarthropathy. The SSA group consisted of ankylosing spondylitis (AS, 40 patients), Reiter's syndrome (RS, 6) and SSA undifferentiated (SSA-U, 17). The chief clinical and radiological features of the group were due to sacro-iliitis/spondylitis, peripheral arthritis and enthesopathy. Except for RS, extra-articular features were sparse. Mucosal lesions were not evident. Radiologically, sacro-iliitis varied from 24% in SSA-U to 100% in AS, and was disproportionately less when compared to its clinical extent. Dominant lower limb arthritis (poly and oligo) was seen in AS (40%), SSA-U (88.2%) and RS (100%). HLA A and B were typed in patients and controls. HLA AI had a significant negative association (p less than 0.05) with AS and the SSA group, and its relative risk (R) was consistently low (0.2-0.3). HLA B27 was present in 65.7%, 73%, 67%, 41% and 9% of the SSA group, AS, RS, SSA-U and controls respectively (p less than 0.05). Significant R values of A and B loci antigens in disease groups are presented. When compared with available Indian literature, this study highlights the variability and overlap in the disease. Disease markers currently available have limitations in defining the various subsets of SSA.