Evaluation of plasma anti-GPL-core IgA and IgG for diagnosis of disseminated non-tuberculous mycobacteria infection

Abstract

Detection of IgA antibody against Mycobacterium avium complex (MAC) glycopeptidolipid (GPL) has recently been shown to improve the diagnosis of MAC pulmonary disease but has yet to be tested in disseminated Non-tuberculous mycobacteria (NTM) infection. In this study, we address the diagnostic efficacies of an anti-GPL-core ELISA kit in disseminated lymphadenopathy patients positive for NTM culture and anti-IFN-γ autoantibodies. The study was conducted in a tertiary referral center in northeastern Thailand and patients with NTM, tuberculosis, melioidosis, and control subjects were enrolled. Plasma immunoglobulin A (IgA) and G (IgG) antibodies against GPL-core were detected in the subjects and the specificity and sensitivity of the assay was assessed. Anti-GPL-core IgA and IgG levels were significantly higher in NTM patients than other groups (p < 0.0001). Diagnostic efficacy for NTM patients using anti-GPL-core IgA cut-off value of 0.352 U/ml showed good sensitivity (91.18%) and intermediate specificity (70.15%). Using a cut-off value of 4.140 AU/ml for anti-GPL-core IgG showed the same sensitivity (91.18%) with increased specificity (89.55%) and an 81.58% positive predictive value. Most patients with moderate levels (4.140–7.955 AU/ml) of anti-GPL-core IgG had rapidly growing mycobacteria (RGM) infection. Taken together, the detection of anti-GPL-core antibodies could provide a novel option for the diagnosis and management of disseminated NTM infected patients.

The Diagnosis of Nontuberculous Mycobacterial Pulmonary Disease by Single Bacterial Isolation Plus Anti-GPL-Core IgA Antibody

“…We also showed that the median time required for the second positive sputum culture was 51 days in our cohort, suggesting the time, cost, and effort-saving effect of using single culture isolation plus anti-GPL-core IgA antibody as another diagnostic criterion. Although the specificity of anti-GPL-core IgA antibodies has been reported to be different between countries ( 7 , 10 , 12 – 14 ), it is still high in many countries. Therefore, we propose adding single culture isolation plus anti-GPL-core IgA antibody as “combined microbiological and serological criteria” to the diagnostic guidelines for MAC-PD and MAB-PD.…”

“…This was a single referral center study, and the participants were all Japanese. Although the positive rate of anti-GPL-core IgA antibodies among healthy individuals is very low in Japan, the USA, and Taiwan ( 7 , 12 , 14 ), it was reported to be quite high in Thailand ( 10 ). The high positive rate of anti-GPL-core IgA antibody among healthy individuals might affect the PPV of single culture isolation plus anti-GPL-core IgA antibody.…”

“…MAC, MAB, Mycobacterium chelonae , Mycobacterium fortuitum , and Mycobacterium scrofulaceum contain GPL whereas M. tuberculosis and other NTM species, including Mycobacterium kansasii , do not ( 8 ). Levels of anti-GPL-core IgA antibody are specifically elevated in the sera of patients with MAC and MAB infections ( 7 , 9 , 10 ). Compared to other isotypes of antibody, anti-GPL-core IgA showed the best sensitivity and specificity for the diagnosis of MAC-PD ( 11 ).…”

“…Compared to other isotypes of antibody, anti-GPL-core IgA showed the best sensitivity and specificity for the diagnosis of MAC-PD ( 11 ). Although geographical differences might exist, it is rare for anti-GPL-core IgA to be casually elevated among patients without MAC or MAB infection ( 7 , 10 , 12 – 14 ). In addition, serum anti-GPL-core IgA is high in patients with early-stage MAC-PD ( 15 ).…”

IgA Serological Response for the Diagnosis of Mycobacterium abscessus Infections in Patients with Cystic Fibrosis

“…Among bacterial infections, the IgA response has been investigated in infections caused by Bordetella pertussis ( 3 ), Chlamydia trachomatis , and mycobacteria, and especially Mycobacterium tuberculosis , with about three quarters of all IgA studies concerning this pathogen within the Mycobacterium genus ( 4 – 8 ). Other mycobacterial infections targeted in IgA serological studies, especially in cystic fibrosis (CF) patients, were Mycobacterium avium ( 9 ) or M. abscessus ( 10 , 11 ).…”