Association of T-cell immunoglobulin and mucin domain-3 gene polymorphism with susceptibility and severity of Mycobacterium avium complex lung disease: a prospective study in Taiwan

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OBJECTIVES: Patients with Mycobacterium avium complex lung disease (MAC-LD) may exhibit immune exhaustion, characterized by elevated T-cell immunoglobulin and mucin domain-3 (TIM3) protein expression on T lymphocytes. Whether single-nucleotide polymorphisms in TIM3 genes are associated with susceptibility to MAC-LD and its clinical presentation remains unknown. METHODS: Patients with MAC-LD and controls were recruited to assess associations between three TIM3 gene single-nucleotide polymorphisms and MAC-LD susceptibility and severity. Disease extent was evaluated using a radiographic score. TIM3-expressing cluster of differentiation (CD)4+ T cells in peripheral blood were quantified by flow cytometry. RESULTS: Higher proportions of TIM3 rs13170556 TC+CC genotype (33% vs 22%, P = 0.042) and females (66% vs 53%, P = 0.037) were found in the MAC-LD group (n = 135) than in controls (n = 139), both independently associated with MAC-LD (odds ratio [OR], 1.752 [95% confidence interval, 1.015-3.025], P = 0.044 and 1.746 [1.068-2.852], P = 0.026). Among the patients, the TIM3 rs13170556 polymorphism was associated with sputum-smear grading >2+ and radiographic scores >5 (OR 2.183 [1.016-4.694], P = 0.046, and 1.960 [1.023-3.755], P = 0.043). The proportion of CD4+ T cells expressing TIM3 was higher in patients with TIM3 rs13170556 TC+CC genotypes than patients with TT genotype (7.1 ± 7.6% vs 4.3 ± 3.4%; P = 0.067) (n = 75). CONCLUSIONS: TIM3 rs13170556 polymorphism is associated with MAC-LD and disease severity, potentially through increased TIM3 protein expression of CD4+ T cells.

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