Diverse humoral immune responses and changes in IgG antibody levels against mycobacterial lipid antigens in active tuberculosis

• Published in: Microbiology (Society for General Microbiology) Vol. 151; no. 6; pp. 2065 - 2074
• Main Authors: Fujita, Yukiko, Doi, Takeshi, Sato, Koji, Yano, Ikuya
• Format: Journal Article
• Language: English
• Published: Reading Soc General Microbiol 01.06.2005; Society for General Microbiology
• Subjects: Adult; Aged; Antibodies, Bacterial - blood; Antigens, Bacterial - immunology; Biological and medical sciences; Cord Factors - immunology; Enzyme-Linked Immunosorbent Assay; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunoglobulin G - blood; Inpatients; Japan; Kinetics; Lipids - immunology; Male; Middle Aged; Molecular immunology; Mycobacterium - immunology; Mycobacterium avium Complex - immunology; Mycobacterium bovis - immunology; Mycobacterium tuberculosis - immunology; Outpatients; Phosphatidylinositols - immunology; Techniques; Time Factors; Tuberculosis - diagnosis; Tuberculosis - immunology; Japan; Immune response; Mycobacterium bovis; IgG; Lipids; Mycobacterial infection; Infection; Antigen; Tuberculosis; Mycobacterium tuberculosis; Mycobacteriales; Bacteriosis; Mycobacteriaceae; Bacteria; Actinomycetes; ELISA assay; Humoral immunity
• ISSN: 1350-0872; 1465-2080
• DOI: 10.1099/mic.0.27790-0

1 Japan BCG Central Laboratory, 3-1-5 Matsuyama, Kiyose-shi, Tokyo 204-0022, Japan 2 National Sanatorium Kumamotominami Hospital, 2338 Toyofuku Matsubase-machi, Shimomashiki-gun, Kumamoto 869-0593, Japan Correspondence Yukiko Fujita y-fujita{at}bcg.gr.jp Humoral immune responses of active TB patients against six mycobacterial lipid antigens [trehalose 6,6'-dimycolate (TDM) from Mycobacterium bovis BCG (TDM-T) and Mycobacterium avium complex (TDM-M), trehalose 6-monomycolate (TMM) from M. bovis BCG (TMM-T) and M. avium complex (TMM-M), triacyl (PL-2) and tetraacyl (PL-1) phosphatidylinositol dimannosides] were examined by ELISA. IgG antibodies of TB patients with active disease reacted against the six lipid antigens distinctively, but heterogeneously. If tests were combined and an overall positive was scored cumulatively when any one of the six tests was positive, a good discrimination between patient and normal subject was obtained. A positive result in any one of the six tests was obtained in 91·5 % of all 924 hospitalized patients and 93·3 % of 210 patients at their first visit to the outpatient clinic. The IgG antibody response differed considerably from patient to patient, and the response patterns were grouped into several types. IgG antibody levels paralleled the bacterial burden; however, the smear-negative (culture-positive) patient group also showed high positive rates and mean ELISA A values against the six lipid antigens. There were also marked differences in positive rate and mean A values between cavity-positive and -negative groups, the former being higher than the latter. After anti-TB chemotherapy was initiated, IgG antibody levels decreased dramatically, paralleling the decrease in the amount of excretion of bacteria. Since multiple-antigen ELISA using particular lipid antigens was highly sensitive, and IgG antibody levels vary greatly at different stages of the disease, this technique is applicable for early diagnosis of smear-negative (and -positive) active TB and the prognosis for completion of anti-TB chemotherapy. Abbreviations: DOTS, directly observed treatment, short course; MAC, M. avium complex; NAA, nucleic acid amplification; PL-1, tetraacyl phosphatidylinositol dimannoside; PL-2, triacyl phosphatidylinositol dimannoside; TDM-M, TDM-T, trehalose 6,6'-dimycolate from M. bovis and M. avium complex, respectively; TMM-M, TMM-T, trehalose 6-monomycolate from M. bovis and M. avium complex, respectively; TB, tuberculosis; TST, tuberculin skin test