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.To control tuberculosis (TB), it is still necessary to find a diagnostic method that is both more rapid to carry out and more sensitive than traditional methods (smear and culture) but which is simpler and less expensive than the new molecular diagnostic tests that are based on the amplification of nucleic acids. Serological methods seem to be the ideal choice and, thus, many mycobacterial antigens have been evaluated: cellular extracts, proteins, and glycolipidic molecules from the mycobacterial cell wall (31). In addition to the lipoarabinomannan antigen, the acylated trehalose family has been the most frequently investigated group of glycolipids. They are 2,3-diacyltrehalose (DAT), 2,3,6-triacyltrehalose (TAT), 2,3,6,6Ј-tetraacyltrehalose 2Ј-sulfate (sulfolipid I [SL-I]), and trehalose-6,6Ј-dimycolate (cord factor [CF]). Using the enzyme-linked immunosorbent assay (ELISA) technique, several studies were performed with these antigens, and an extensive variability in immunoglobulin G (IgG) or IgM titers (6,7,11,18,20,(24)(25)(26) was obtained, i.e., test sensitivities were as different as 11 to 88% for the DAT antigen (11, 25) and 51 to 93% for the TAT antigen (11,26). These contradictory results are due to the ELISA protocol used (the different antigen concentrations or the use of detergent in washing buffers) (15, 30), or to the different sera groups analyzed (the number and type of patients and control subjects) (10). Thus, no definite conclusions as to th...

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

“…In sputum (71). Several lipid moieties have been purified and intensely studied for their serological potential for TB diagnosis (44). Four lipid antigens, all acylated trehaloses (107), were evaluated in smear-positive patients and included in the meta-analysis.…”

Increased Synthesis of Anti-Tuberculous Glycolipid Immunoglobulin G (IgG) and IgA with Cavity Formation in Patients with Pulmonary Tuberculosis

“…Julián et al conducted a comparative study of IgG, IgM, and IgA antibody responses to four trehalose-containing glycolipids, including cord factor, purified from Mycobacterium tuberculosis in the sera from 92 TB patients. They concluded that IgG antibody was more sensitive, IgA antibody was more specific, and IgM reactivity was negligible for all the glycolipid antigens used (10). Since TBGL is a glycolipid antigen containing cord factor, anti-TBGL IgA may yield a higher specificity than does anti-TBGL IgG, and the detection of both anti-TBGL IgG and anti-TBGL IgA may improve the diagnostic value.…”

A study of iga antibody response to different mycobacterium tuberculosis antigens in the diagnosis and monitoring of pulmonary tuberculosis

“…As in other studies [10], the ROC curve was used to determine the best specificity values for the tests without a major loss in sensitivity and to identify the most accurate test (Figure 1). Julian et al (2002) showed that adult tuberculosis patients have a specific IgA response to glycolipid antigens. However, they found that tests detecting immunoglobulin A had lower sensitivity (66%) and greater specificity (88%) than IgG.…”

“…A number of factors can influence the reactivity of the test, such as the patient's immunological "status" and the stage and duration of the disease at the moment that the patient was included in the study [16][17][18]. When the ELISA tests using different antigens were carried out with sera from groups III and IV, there was less variation in specificity with the glycolipid antigen (88%-100%).…”