Differences in serological responses to specific glycopeptidolipid-core and common lipid antigens in patients with pulmonary disease due to Mycobacterium tuberculosis and Mycobacterium avium complex.

Disease due to the Mycobacterium avium complex (MAC) is one of the most important opportunistic pulmonary infections. Since the clinical features of MAC pulmonary disease and tuberculosis (TB) resemble each other, and the former is often difficult to treat with chemotherapy, early differential diagnosis is desirable. The humoral immune responses to both diseases were compared by a unique multiple-antigen ELISA using mycobacterial species-common and species-specific lipid antigens, including glycopeptidolipid (GPL)-core. The results were assessed for two patient groups hospitalized and diagnosed clinically as having TB or MAC pulmonary disease. Diverse IgG antibody responsiveness was demonstrated against five lipid antigens: (1) monoacyl phosphatidylinositol dimannoside (Ac-PIM2), (2) cord factor (trehalose 6,6'-dimycolate) (TDM-T) and (3) trehalose monomycolate from Mycobacterium bovis Bacillus Calmette-Guérin (BCG) (TMM-T), and (4) trehalose monomycolate (TMM-M) and (5) GPL-core from MAC. Anti-GPL-core IgG antibody was critical, and detected only in the primary and the secondary MAC diseases with high positivity, up to 88.4 %. However, IgG antibodies against Ac-PIM2, TDM-T and TMM-T were elevated in both TB and MAC patients. Anti-TMM-M IgG antibody was also elevated in MAC disease preferentially, with a positive rate of 89.9 %, and therefore, it was also useful for the diagnosis of the disease. IgG antibody levels were increased at the early stages of the disease and declined in parallel to the decrease of bacterial burden to near the normal healthy control level, when the anti-mycobacterial chemotherapy was completed successfully. Unexpectedly, about 25 % of hospitalized TB patient sera were anti-GPL-core IgG antibody positive, although the specificity of GPL-core was sufficiently high (95.8 % negative in healthy controls), suggesting that a considerable number of cases of latent co-infection with MAC may exist in TB patients. Taken together, the combination of multiple-antigen ELISA using mycobacterial lipids, including GPL-core and TMM-M, gives good discrimination between healthy controls and sera from patients with TB or MAC disease, although for accurate diagnosis of TB more specific antigen(s) are needed.

[1]  I. Yano,et al.  Rapid serodiagnosis of human mycobacteriosis by ELISA using cord factor (trehalose-6,6'-dimycolate) purified from Mycobacterium tuberculosis as antigen. , 1991, FEMS microbiology immunology.

[2]  P. Venkatesan,et al.  Isolation and Identification of Environmental Mycobacteria in the Mycobacterium bovis BCG Trial Area of South India , 1994, Applied and environmental microbiology.

[3]  Kazuo Kobayashi,et al.  Clinical and Prognostic Importance of Serotyping Mycobacterium avium-Mycobacterium intracellulare Complex Isolates in Human Immunodeficiency Virus-Negative Patients , 2005, Journal of Clinical Microbiology.

[4]  T. Kuroki,et al.  Rapid Serodiagnosis of Mycobacterium avium‐intracellulare Complex Infection by ELISA with Cord Factor (Trehalose 6, 6′‐Dimycolate), and Serotyping Using the Glycopeptidolipid Antigen , 1998, Microbiology and immunology.

[5]  I. Yano,et al.  Clinical Evaluation of Anti-Tuberculous Glycolipid Immunoglobulin G Antibody Assay for Rapid Serodiagnosis of Pulmonary Tuberculosis , 2001, Journal of Clinical Microbiology.

[6]  Trial of BCG vaccines in south India for tuberculosis prevention: first report--Tuberculosis Prevention Trial. , 1979, Bulletin of the World Health Organization.

[7]  E. L. Wright,et al.  Modified lymphocyte response to mitogens induced by the lipopeptide fragment derived from Mycobacterium avium serovar-specific glycopeptidolipids , 1992, Infection and immunity.

[8]  B. Parker,et al.  Epidemiology of Infection by Nontuberculous Mycobacteria , 1987 .

[9]  E. Ueda,et al.  Clinical evaluation of rapid serodiagnosis of pulmonary tuberculosis by ELISA with cord factor (trehalose-6,6'-dimycolate) as antigen purified from Mycobacterium tuberculosis. , 1993, The American review of respiratory disease.

[10]  D. Girling,et al.  Serodiagnosis of tuberculosis using an ELISA with antigen 5 and a hemagglutination assay with glycolipid antigens. Results in patients with newly diagnosed pulmonary tuberculosis ranging in extent of disease from minimal to extensive. , 1990, The American review of respiratory disease.

[11]  C. Palmer,et al.  Effects of infection with atypical mycobacteria on BCG vaccination and tuberculosis. , 1966, The American review of respiratory disease.

[12]  J. Grange,et al.  Diagnosis of active tuberculosis by immunological methods. 1. The effect of tuberculin reactivity and previous BCG vaccination on the antibody levels determined by ELISA. , 1982, Tubercle.

[13]  I. Yano,et al.  New diagnostic approach for ocular tuberculosis by ELISA using the cord factor as antigen , 2001, The British journal of ophthalmology.

[14]  N. Fujiwara,et al.  Anti‐Cord Factor (Trehalose 6,6′‐Dimycolate) IgG Antibody in Tuberculosis Patients Recognizes Mycolic Acid Subclasses , 1999, Microbiology and immunology.

[15]  T. Ottenhoff,et al.  Genetics, cytokines and human infectious disease: lessons from weakly pathogenic mycobacteria and salmonellae , 2002, Nature Genetics.

[16]  Nalin Rastogi,et al.  Exposure of human peripheral blood mononuclear cells to total lipids and serovar-specific glycopeptidolipids from Mycobacterium avium serovars 4 and 8 results in inhibition of TH1-type responses. , 2000, Microbial pathogenesis.

[17]  C. F. von Reyn,et al.  Evidence of previous infection with Mycobacterium avium-Mycobacterium intracellulare complex among healthy subjects: an international study of dominant mycobacterial skin test reactions. , 1993, The Journal of infectious diseases.

[18]  Koji Sato,et al.  Diverse humoral immune responses and changes in IgG antibody levels against mycobacterial lipid antigens in active tuberculosis. , 2005, Microbiology.

[19]  I. Yano,et al.  Rapid identification of serotypes of Mycobacterium avium-M. intracellulare complex by using infected swine sera and reference antigenic glycolipids , 1989, Journal of clinical microbiology.

[20]  I. Yano,et al.  Enzyme immunoassay to detect antituberculous glycolipid antigen (anti‐TBGL antigen) antibodies in serum for diagnosis of tuberculosis , 1997, Journal of clinical laboratory analysis.

[21]  H. Nikaido,et al.  The envelope of mycobacteria. , 1995, Annual review of biochemistry.

[22]  P. Fine,et al.  Environmental mycobacteria in northern Malawi: implications for the epidemiology of tuberculosis and leprosy , 2001, Epidemiology and Infection.

[23]  H. Tomioka,et al.  Identification of various serovar strains of Mycobacterium avium complex by using DNA probes specific for Mycobacterium avium and Mycobacterium intracellulare , 1990, Journal of clinical microbiology.

[24]  A. Mackellar Diagnosis and management of atypical mycobacterial lymphadenitis in children. , 1976, Journal of pediatric surgery.

[25]  R. Wallace,,et al.  Diagnosis and treatment of disease caused by nontuberculous mycobacteria. , 1990, The American review of respiratory disease.

[26]  J. Falkinham,et al.  Epidemiology of infection by nontuberculous mycobacteria , 1996, Clinical microbiology reviews.

[27]  Kazuo Kobayashi,et al.  Use of Glycopeptidolipid Core Antigen for Serodiagnosis of Mycobacterium avium Complex Pulmonary Disease in Immunocompetent Patients , 2005, Clinical Diagnostic Laboratory Immunology.

[28]  I. Yano,et al.  Prospective Clinical Evaluation of the Serologic Tuberculous Glycolipid Test in Combination with the Nucleic Acid Amplification Test , 2003, Journal of Clinical Microbiology.

[29]  Kazuo Kobayashi,et al.  Serodiagnosis of pulmonary disease due to Mycobacterium avium complex with an enzyme immunoassay that uses a mixture of glycopeptidolipid antigens. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[30]  I. Yano,et al.  Detection of anti-cord factor antibodies in intestinal tuberculosis for its differential diagnosis from Crohn's disease and ulcerative colitis , 1995, Digestive diseases and sciences.

[31]  P. Venkatesan,et al.  Immune response & modulation of immune response induced in the guinea-pigs by Mycobacterium avium complex (MAC) & M. fortuitum complex isolates from different sources in the south Indian BCG trial area. , 1996, The Indian journal of medical research.

[32]  J. Lamprecht,et al.  Cervical lymphadenitis due to mycobacteria other than tuberculosis--an emerging problem in children? , 1995, ORL; journal for oto-rhino-laryngology and its related specialties.