Differential levels of anti-Mycobacterium tuberculosis-specific IgAs in saliva of household contacts with latent tuberculosis infection

Abstract

IntroductionMucosal immunity is strongly elicited in early stages of many respiratory and enteric infections; however, its role in tuberculosis pathogenesis has been scarcely explored. We aimed to investigate Mycobacterium tuberculosis (Mtb) specific IgA levels in saliva in different stages of latent Tuberculosis Infection (TBI).MethodologyA multiplex bead-based Luminex immunoassay was developed to detect specific IgA against 12 highly immunogenic Mtb antigens. A prospective cohort of household contacts (>14 years) of pulmonary TB cases was established in Santiago, Chile. Contacts were classified as Mtb-infected or not depending on serial interferon-γ release assay results. Saliva samples were collected and tested at baseline and at a 12-week follow-up.ResultsMtb-specific IgA was detectable at all visits in all participants (n = 168), including the “non-Mtb infected” (n = 64). Significantly higher median levels of IgA were found in the “Mtb infected” compared to the uninfected for anti-lipoarabinomannan (LAM) (110 vs. 84.8 arbitrary units (AU), p < 0.001), anti-PstS1 (117 vs. 83 AU, p < 0.001), anti-Cell Membrane Fraction (CMF) (140 vs. 103 AU, p < 0.001) and anti-Culture Filtrate Proteins (CFP) (median 125 vs. 96 AU, p < 0.001), respectively. Nonetheless, the discriminatory performance of these specific mucosal IgA for TBI diagnosis was low.ConclusionSaliva holds Mtb-specific IgA against several antigens with increased levels for anti-LAM, anti-PstS1, anti-CMF and anti-CFP found in household contacts with an established TBI. The role of these mucosal antibodies in TB pathogenesis, and their kinetics in different stages of Mtb infection merits further exploring.