IL10 Haplotype Associated with Tuberculin Skin Test Response but Not with Pulmonary TB

Abstract

Evidence from genetic association and twin studies indicates that susceptibility to tuberculosis (TB) is under genetic control. One gene implicated in susceptibility to TB is that encoding interleukin-10 (IL10). In a group of 2010 Ghanaian patients with pulmonary TB and 2346 healthy controls exposed to Mycobacterium tuberculosis, among them 129 individuals lacking a tuberculin skin test (PPD) response, we genotyped four IL10 promoter variants at positions 22849 , 21082 , 2819 , and 2592 and reconstructed the haplotypes. The IL10 low-producer haplotype 22849A/21082A/2819C/2592C, compared to the high-producer haplotype 22849G/21082G/2819C/2592C, occurred less frequent among PPD-negative controls than among cases (OR 2.15, CI 1.3–3.6) and PPD-positive controls (OR 2.09, CI 1.2–3.5). Lower IL-10 plasma levels in homozygous 22849A/21082A/2819C/2592C carriers, compared to homozygous 22849G/21082G/2819C/2592C carriers, were confirmed by a IL-10 ELISA (p = 0.016). Although we did not observe differences between the TB patients and all controls, our results provide evidence that a group of individuals exposed to M. tuberculosis transmission is genetically distinct from healthy PPD positives and TB cases. In these PPD-negative individuals, higher IL-10 production appears to reflect IL-10-dependent suppression of adaptive immune responses and sustained long-term specific anergy.