Isotype-specific Anti-38 and 27 kDa (mpt 51) Response in Pulmonary Tuberculosis with Human Immunodeficiency Virus Coinfection

Abstract

There is a need for rapid diagnostic methods to identify tuberculosis among human immunodeficiency virus-positive cases (HIV-TB). This study evaluated the serodiagnostic potential of the native 38 kDa and recombinant 27 kDa (mpt 51) antigens of Mycobacterium tuberculosis purified in the laboratory, when applied to HIV-TB patients. The antibody response was studied using enzyme-linked immunosorbent assays (ELISA). In the HIV-TB group, anti-38 kDa antibody of the immunoglobulin G (IgG), IgA and IgM isotypes was found in 38%, 43% and 7%, of patients, respectively. Antibodies to the 27 kDa antigen occurred in 50%, 31%, and 1%, for IgG, IgA and IgM, respectively. The sensitivity increased upon combination of the results of IgG and IgA isotypes for each of the antigens, without compromising specificity. When the results were analysed based on the smear positivity, 71-78% and 54-69% were positive among smear-positive and smear-negative HIV-TB cases, respectively. A higher sensitivity (71% and 69%) was obtained using the 27 kDa antigen. The use of both antigens offered a sensitivity of 82% in smear-positive and 69% in smear-negative cases. There was no difference in antibody response among the HIV-TB cases, related to CD4 counts. Thus, the combination of the 38 and 27 kDa (mpt 51) antigens proved to be of diagnostic utility in HIV-TB, irrespective of the severity of immunosuppression, in smear-positive and smear-negative TB.

Performance of Purified Antigens for Serodiagnosis of Pulmonary Tuberculosis: a Meta-Analysis

“…In sputum smear-negative patients, the sensitivity reported was lower (31%; 95% CI, 15 to 52). Specificities were 97% in both subgroups (15,18,59,69,76,77,102).…”

“…A sufficient number of studies evaluating the performance of MPT51 were available to stratify the results by HIV infection status. In sputum smear-positive patients, MPT51 provided equivalent sensitivities in both HIV-negative TB patients (59%; 95% CI, 38 to 76) and HIV-positive TB patients (58%; 95% CI, 30 to 82); the specificities were 94% and 97%, respectively (10,69,85,108).…”

“…However, only 6 (20%) studies involved controls with nontuberculous respiratory disease (23,35,37), while 14 (47%) studies involved either healthy volunteers or asymptomatic HIV-infected individuals without TB (35,37,103,108). In 10 (33%) studies, the control group involved HIV-infected individuals whose clinical status ranged from asymptomatic to symptomatic with opportunistic infections other than TB (69).…”

“…Thirty studies evaluating antigens (all proteins) in HIV-infected TB patients were identified; all studies involved sputum smear-positive patients. Of the total, 23 (77%) studies evaluated assays for the detection of IgG and/or IgA antibodies (23,35,37,69,103,108), four studies evaluated assays for the detection of IgM (69,103). Four studies based on multiple-antigen combinations are described in more detail below (35,37,108).…”

Identification of an HLA-A*0201-Restricted T-Cell Epitope on the MPT51 Protein, a Major Secreted Protein Derived fromMycobacterium tuberculosis, by MPT51 Overlapping Peptide Screening

“…Importantly, MPT51 has been reported to be a potential marker for the diagnosis of TB, especially in AIDS patients. Ramalingam and colleagues (26) reported that early immune responses against 38-and 27-kDa (MPT51) proteins were detected in pulmonary TB patients, accompanied by human immunodeficiency virus coinfection. In addition, we demonstrated that MPT51 DNA vaccination using an attenuated Listeria carrier vaccination system induced protection against M. tuberculosis infection in mice (20).…”