HLA-DR2 subtypes & immune responses in pulmonary tuberculosis.

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 micrograms/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.

Influence of non-MHC genes on lymphocyte response to Mycobacterium tuberculosis antigens & tuberculin reactive status in pulmonary tuberculosis.

BACKGROUND & OBJECTIVES: Major histocompatibility complex (MHC) genes are known to influence the immune functions. In the present study, the influence of non-MHC genes such as mannose binding protein (MBP), vitamin D receptor (VDR) and interleukin-1 receptor antagonist (IL-1RA) gene polymorphisms on lymphocyte response to Mycobacterium tuberculosis culture filtrate antigen (10 micrograms/ml) was studied in 44 patients with active pulmonary TB and the family contacts (35) and in 32 normal healthy subjects. The influence of these gene polymorphisms on tuberculin (1TU of PPD of M. tuberculosis) reactivity status in 146 pulmonary TB patients was also studied. METHODS: The MBP and VDR genes were amplified using polymerase chain reaction (PCR) and genotyping was carried out using sequence specific oligonucleotide probes by dot blot and IL-1RA by agarose gel electrophoresis. RESULTS: A significantly decreased lymphocyte response to M. tuberculosis antigen was seen in pulmonary TB patients positive for functional mutant homozygotes of MBP (OO) compared to heterozygote carriers (AO; P < 0.02) and wild homozygotes (AA; P < 0.01). The variant mutant genotype (tt) of VDR gene was associated with an increased lymphocyte response in control subjects compared to active TB patients with tt genotype (P < 0.05). Heterozygote carriers of MBP (AO) were associated with a significantly (P < 0.001) decreased tuberculin reactivity compared to wild homozygotes (AA). The VDR genotype Tt (heterozygote carrier) was associated with an increased tuberculin reactivity in female TB patients as compared to male patients (P < 0.001). INTERPRETATION & CONCLUSIONS: The present study suggested that MBP and VDR genes influence the cell mediated immune response in pulmonary TB patients. Non-MHC genes along with HLA-Class II genes/gene products may be playing an immunoregulatory role in the mechanism of susceptibility/resistance to tuberculosis.

HLA antigen profile in pulmonary tuberculosis patients & their spouses.

HLA-A, -B, -DR and -DQ antigen profile was studied in pulmonary tuberculosis patients (n = 209) and their spouses (family contacts; n = 50) and healthy volunteers (n = 72). An increased frequency of HLA-A-10, B7, B15, DR2 and DQ1 was seen in the pulmonary-TB (PTB) patients when compared to the total control subjects (n = 122). However, a significant increase was seen only with HLA-DR2 (P < 0.001; Pc < 0.01; Relative Risk 2.3) and -DQ1 (P < 0.005; Pc < 0.015; Relative Risk 2.8). Among the spouses and the corresponding patients, a similar increase of HLA-DR2 was seen. A decreased frequency of HLA-A19, B8, B17, B35, DR5 and DR6 were seen in PTB as compared to control groups. The present study suggested that HLA-DR2 and DQ1 genes/gene products may be associated with the susceptibility to tuberculosis either alone or in combination with other HLA or non-HLA genes.