It has been estimated that only 10% of persons infected with Mycobacterium tuberculosis will ever develop clinical disease. As for the host genetic factors, there have been some studies on HLA association with tuberculosis susceptibility, however its association with disease severity or drug resistance has been rarely reported. To investigate the association of HLA polymorphism and disease susceptibility to pulmonary tuberculosis, HLA-DRB1 and DQB1 genes were analyzed in 160 Korean patients with pulmonary tuberculosis (PTB) and 200 healthy controls using reverse SSO, PCR-RFLP and PCR-SSCP methods. We also analyzed HLA polymorphisms according to the extent of lung lesion, history of treatment/disease recurrence and drug susceptibility. Compared to controls, PTB patients showed significantly increased frequencies of DRB1*0803 (14.5% vs 25.0%, ORϭ1.97, pϭ0.01) and a closely linked DQB1 allele, DQB1*0601 (15.5% vs 27.5%, ORϭ2.07, pϭ0.005). The phenotype frequency of DRB1*0803 was higher in patient group with more severe (moderately or far-advanced) than minimal lung lesion (29.8% vs 3.4%, pϭ0.003), in re-treated/recurrent than initially treated group (37.7% vs 18.7%, pϭ0.009), and in drug-resistant than drug-susceptible group (30.9% vs 20.0%, pϭ0.14). DQB1*0601 showed similar, but less significant changes in these three categories of comparison. Our results suggest that HLA-DRB1*0803, DQB1*0601 or other closely linked MHC alleles are associated with genetic susceptibility to PTB in Koreans, and individuals carrying these genetic factors are considered to mount a poor immune response to Mycobacterial pathogens resulting in progression to more severe disease, recurrence of disease, and development of drug resistance.
#186PEMPHIGUS VULGARIS IN JEWISH PATIENTS IS ASSOCIATED ALSO WITH HLA-A REGION Pemphigus vulgaris (PV) is the most severe autoimmune blistering disorder of the skin. It has been reported that in Jews the associated haplotypes in PV is HLA-B38, DRB1*0402, DQB1*0302. Significant associations with these and other HLA antigens and/or haplotypes were also observed in non-Jews. This suggests that genes other than the Class II MHC genes are associated with the development of the auto immune response. We used 16 microsatellite probes which span the entire MHC region to screen DNA samples from 38 PV patients and 76 healthy controls. Results showed that some markers were associated with class-II region including a TAP associated marker. However, three probes, D6S265, C_ 5-2-7 and MOGCA which are all mapped to the region of HLA-A were highly associated with PV (pϽ0.001). These results suggest that a gene, or genes in the class-I region are important in the initiation of the auto-immune cascade. Activation/suppression of these genes might act as the trigger mechanism which starts the auto-immune destructive process.
S139Abstracts
