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

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

Indian Journal of Medical Research; 2000; 112; 86-92.          

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 mg/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 homzygotes (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.

Key words : Gene polymorphisms - IL-1RA - lymphocyte response - MBP - Mycobacterium tuberculosis - pulmonary-TB tuberculin reaction - VDR

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