HLA-DR2 subtypes & immune responses in pulmonary tuberculosis.

Uma Sriram; Selvaraj, P.; Kurian, S.M.; Reetha, A.M.; Narayanan, P.R.

Indian Journal of Medical Research; 2001; 113; 117-124 .        

Background & objectives : HLA-DR2 has been shown to be associated with the susceptibility to pulmonary tuberculosis and altered antibody and lymphocyte response in pulmonary tuberculosis. In the present study, the influence of DR2 subtypes on antibody titre and lymphocyte response to Mycobacterium tuberculosis culture filtrate antigens (10 m g/ml) was studied in 22 patients with active pulmonary TB (ATB), 50 inactive (cured) TB (ITB) patients and 36 healthy control subjects.

Methods : HLA-DR2 gene was amplified by polymerase chain reaction (PCR) and dot-blotted. Genotyping of DRB1*1501, *1502, *1503, *1601 and *1602 was carried out using sequence specific oligonucleotide probes (SSOPs) and detected by chemiluminescence method. Antibody titre as well as lymphocyte response to M. tuberculosis antigens were measured by enzyme linked immunosorbent assay (ELISA) and lymphocyte transformation test (LTT) respectively.

Results : The allele frequency of DRB1*1501 was significantly increased in pulmonary tuberculosis patients as compared to controls ( P <0.05). No marked difference in the antibody titre and lymphocyte response to M. tuberculosis antigens was observed between the DRB1 *1501, *1502 and *1503 positive or negative controls, ATB and ITB patients. DRB1 *1501 and *1502 positive as well as negative ATB patients showed a higher antibody titre as compared to controls and ITB patients. ITB patients with *1502 showed a higher lymphocyte response as compared to *1502 positive controls ( P <0.001) and ATB patients ( P <0.05). Similarly, an increased lymphocyte response was observed in *1501 and *1503 negative ITB patients compared to *1501 and *1503 negative controls and ATB patients.

Interpretation & conclusion : The present study revealed that DRB1 *1501 may be associated either alone or with other DR2 alleles, with the susceptibility to pulmonary tuberculosis. None of the DR2 alleles influenced the antibody and lymphocyte response to M. tuberculosis culture filtrate antigens. This suggested that HLA-DR2 gene/gene products as a whole may influence the immune response in pulmonary tuberculosis.

Key words : HLA-DR2 subtypes - immune response - Mycobacterium tuberculosis - pulmonary tuberculosis

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