Influence of HLA-DRB1 alleles on Th1 and Th2 cytokine response to Mycobacterium tuberculosis antigens in pulmonary tuberculosis.

Selvaraj, P.; Rajeswari D.N.; Jawahar, M.S.; Narayanan, P.R.

Tuberculosis (Edinb).2007; 87; 544-550 .

Summary: The influence of human leukocyte antigens (HLA) on the immune response is well established. We investigated the regulatory role of HLA-DRB1 alleles on cytokine response to live M. tuberculosis and its culture filtrate antigen (CFA) in normal healthy subjects (NHS) and pulmonary tuberculosis (PTB) patients. Th1 (IFN- g and IL-12p40), Th2 (IL-4 and IL-5), pro-inflammatory (IL-6 and IL-8) and anti-inflammatory (TGF- b and IL-10) cytokines were measured by ELISA in 72-h-old peripheral blood mononuclear cell culture supernatants from 58 NHS and 48 PTB patients. HLA-DRB1 genotyping was carried out by polymerase chain reaction and dot-blot hybridization with biotinylated sequence-specific oligonucleotide probes and detection by chemiluminescence. In response to live M. tuberculosis and CFA, significantly increased levels of IL-6, IL-8 and TGF- b and decreased IFN- g , IL-12p40 and IL-10 were seen in PTB patients compared to NHS. We observed a significantly increased IFN- g response in HLA-DRB1*03-positive NHS ( p = 0.03) and decreased IFN- g response in HLA-DRB1*15-positive patients ( p = 0.04) than respective allele-negative individuals. An increased level of IL-12p40 in DRB1*10 ( p = 0.02) and IL-10 in DRB1*12- ( p = 0.03) positive NHS and an increased level of IL-6 in DRB1*04- ( p = 0.02) positive patients were observed. The study suggests that HLA-DRB1 alleles differentially modulate the various cytokine responses to M. tuberculosis antigens, which may influence the cellular and humoral immune responses to M. tuberculosis infection in a susceptible host.

Keywords: HLA-DRB1 alleles; Cytokines; Pulmonary tuberculosis

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