Human Leukocyte Antigen-G (HLA-G) 14-bp deletion polymorphism is associated with decreased risk of pulmonary fibrosis in Indonesian Javanese patients with multidrug-resistant tuberculosis

Abstract

Background: Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I antigen with immunomodulatory activity that usually inhibits immune responses. The role of the HLA-G polymorphism in multidrug-resistant tuberculosis (MDR-TB) is unknown. Objectives: To analyze clinical data from Indonesian Javanese patients with MDR-TB to find an association between the HLA-G polymorphism and MDR-TB. Methods: Fifty-seven Indonesian Javanese patients with MDR-TB were enrolled and monitored from May 2012 to Jan 2014. Non-TB individuals and non-MDR-TB individuals were recruited as controls. The HLA-G polymorphism status of each patient was determined by polymerase chain reaction. Patient clinical data were analyzed against polymorphism status. The presence of an association was estimated with an odds ratio (OR) and 95% confidence interval (CI) calculated via logistic regression. Results: Nineteen (33.3%), 30 (52.6%), and 8 (14.1%) MDR-TB patient participants carried a homozygous deletion (D/D), heterozygous deletion (I/D), and homozygous insertion (I/I) genotypes, respectively. Among control participants, D/D genotype carriers less frequently had a history of TB infection (OR 0.4, 95% CI 0.179-0.981, P = 0.043). The deletion allele for MDR-TB patients was associated with a decreased likelihood of developing pulmonary fibrosis (adjusted OR 0.1, 95% CI 0.014-0.639, P = 0.016). Conclusions: D/D genotype carriers are less susceptible to TB, and MDR-TB patients with a deletion allele are less likely to develop pulmonary fibrosis. Keywords: HLA-G, Indonesia, MDR-TB, polymorphism, tuberculosis