Serodiagnosis of tuberculosis: comparison of immunoglobulin A (IgA) response to sulfolipid I with IgG and IgM responses to 2,3-diacyltrehalose, 2,3,6-triacyltrehalose, and cord factor antigens

Abstract

Nonpeptidic antigens from the Mycobacterium tuberculosis cell wall are the focus of extensive studies to determine their potential role as protective antigens or serological markers of tuberculous disease. Regarding this latter role and using an enzyme-linked immunosorbent assay, we have made a comparative study of the immunoglobulin G (IgG), IgM, and IgA antibody responses to four trehalose-containing glycolipids purified from M. tuberculosis: diacyltrehaloses, triacyltrehaloses, cord factor, and sulfolipid I (SL-I). Sera from 92 tuberculosis patients (taken before starting antituberculosis treatment) and a wide group of control individuals (84 sera from healthy donors, including purified protein derivative-negative, -positive, healed, and vaccinated individuals, and 52 sera from nontuberculous pneumonia patients), all from Spain, were studied. The results indicated a significantly elevated IgG and IgA antibody response in tuberculosis patients, compared with controls, with all the antigens used. SL-I was the best antigen studied, showing test sensitivities and specificities for IgG of 81 and 77.6%, respectively, and of 66 and 87.5% for IgA. Using this antigen and combining IgA and IgG antibody detection, high test specificity was achieved (93.7%) with a sensitivity of 67.5%. Currently, it is widely accepted that it is not possible to achieve sensitivities above 80% in tuberculosis serodiagnosis when using one antigen alone. Thus, we conclude that SL-I, in combination with other antigenic molecules, could be a useful antigen for tuberculosis serodiagnosis.

FIG. 1.

Results of the ELISA for glycolipids in sera from adult subjects. Individual absorbance values for each test are shown. Each dot indicates an individual serum sample. The dotted line indicates cutoff values above which a test is positive (mean + 3 SD of the healthy population values). Pulm TB, pulmonary TB; Extra TB, extrapulmonary TB; PPD−, healthy PPD negative; PPD+, healthy PPD positive; Vaccin, healthy vaccinated; Healed, healthy healed; Mycob, other mycobacterial diseases; and Other resp dis, other respiratory diseases.

FIG. 1.

Results of the ELISA for glycolipids in sera from adult subjects. Individual absorbance values for each test are shown. Each dot indicates an individual serum sample. The dotted line indicates cutoff values above which a test is positive (mean + 3 SD of the healthy population values). Pulm TB, pulmonary TB; Extra TB, extrapulmonary TB; PPD−, healthy PPD negative; PPD+, healthy PPD positive; Vaccin, healthy vaccinated; Healed, healthy healed; Mycob, other mycobacterial diseases; and Other resp dis, other respiratory diseases.