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.

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Clinical evaluation of serodiagnosis of active tuberculosis by multiple-antigen ELISA using lipids from Mycobacterium bovis BCG Tokyo 172

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2005.216 ◽

2005 ◽

Vol 43 (11) ◽

Cited By ~ 10

Author(s):

Yukiko Fujita ◽

Hideo Ogata ◽

Ikuya Yano

Keyword(s):

Immune Responses ◽

Mycobacterium Bovis ◽

Clinical Evaluation ◽

Active Tuberculosis ◽

Mycobacterium Bovis Bcg ◽

Lipid Antigens ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Antigen Elisa ◽

Multiple Antigen

AbstractThe humoral immune responses of 69 active tuberculosis (TB) patients against three major mycobacterial lipid antigens, monoacyl phosphatidylinositol dimannoside (Ac-PIM

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

Microbiology ◽

10.1099/mic.0.27790-0 ◽

2005 ◽

Vol 151 (6) ◽

pp. 2065-2074 ◽

Cited By ~ 24

Author(s):

Yukiko Fujita ◽

Takeshi Doi ◽

Koji Sato ◽

Ikuya Yano

Keyword(s):

Immune Responses ◽

Response Patterns ◽

Igg Antibody ◽

Lipid Antigens ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Antigen Elisa ◽

Positive Rate ◽

Smear Negative ◽

Antibody Levels

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 ΔA values against the six lipid antigens. There were also marked differences in positive rate and mean ΔA 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.

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Recurrence of Disseminated Mycobacterium avium Complex Disease in a Patient with Anti-Gamma Interferon Autoantibodies by Reinfection

Journal of Clinical Microbiology ◽

10.1128/jcm.03339-14 ◽

2015 ◽

Vol 53 (4) ◽

pp. 1436-1438 ◽

Cited By ~ 10

Author(s):

Tomoyasu Nishimura ◽

Yukiko Fujita-Suzuki ◽

Makoto Yonemaru ◽

Kiyofumi Ohkusu ◽

Takuro Sakagami ◽

...

Keyword(s):

Disease Activity ◽

Mycobacterium Avium ◽

Mycobacterium Avium Complex ◽

Complex Disease ◽

Gamma Interferon ◽

Igg Antibody ◽

Content Type ◽

Lipid Antigens ◽

Antibody Titers ◽

Mycobacterium Avium Complex Disease

We report a case of recurrent disseminatedMycobacterium aviumcomplex (DMAC) disease with anti-gamma interferon autoantibodies. To our knowledge, this is the first reported case caused by reinfection with a separate isolate ofM. avium. DMAC disease activity was monitored using serum IgG antibody titers against lipid antigens extracted from a MAC strain.

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Cellular Immune Responses to ESAT-6 Discriminate between Patients with Pulmonary Disease Due to Mycobacterium avium Complex and Those with Pulmonary Disease Due toMycobacterium tuberculosis

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.6.4.606-609.1999 ◽

1999 ◽

Vol 6 (4) ◽

pp. 606-609 ◽

Cited By ~ 55

Author(s):

A. David Lein ◽

C. Fordham von Reyn ◽

Pernille Ravn ◽

C. Robert Horsburgh ◽

Lorraine N. Alexander ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Pulmonary Disease ◽

Mycobacterium Avium ◽

Mononuclear Cells ◽

Negative Control ◽

Healthy Controls ◽

Peripheral Blood Mononuclear ◽

Ifn Γ ◽

Cellular Immune

ABSTRACT ESAT-6 (for 6-kDa early secreted antigenic target) is a secreted antigen found almost exclusively in organisms of theMycobacterium tuberculosis complex. We compared in vitro gamma interferon (IFN-γ) responses by peripheral blood mononuclear cells to this antigen in patients with pulmonary disease due to eitherMycobacterium avium complex (MAC) or Mycobacterium tuberculosis with those in healthy, skin test-negative, control subjects. Significant IFN-γ responses to ESAT-6 were detected in 16 (59%) of 27 M. tuberculosis pulmonary disease patients, 0 (0%) of 8 MAC disease patients, and 0 (0%) of 8 controls. Significant IFN-γ responses to M. tuberculosis purified protein derivative were detected in 23 (85%) of 27 M. tuberculosisdisease patients, 2 (25%) of 8 MAC disease patients, and 5 (63%) of 8 healthy controls. M. avium sensitin was recognized in 24 (89%) of 27 M. tuberculosis disease patients, 4 (50%) of 8 MAC disease patients, and 1 (13%) of 8 controls. IFN-γ responses to ESAT-6 are specific for disease due toM. tuberculosis and are not observed in patients with MAC disease or in healthy controls.

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Faculty Opinions recommendation of Serial CT findings of nodular bronchiectatic Mycobacterium avium complex pulmonary disease with antibiotic treatment.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718124118.793487738 ◽

2013 ◽

Author(s):

David Griffith

Keyword(s):

Pulmonary Disease ◽

Antibiotic Treatment ◽

Mycobacterium Avium ◽

Mycobacterium Avium Complex ◽

Ct Findings ◽

Serial Ct

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Nontuberculous Mycobacterium Infections in Rheumatoid Arthritis Patients: The Serodiagnosis of Pulmonary Disease due to Mycobacterium avium Complex with an Enzyme Immunoassay Kit Detecting Glycopeptidolipid Core Antigen (Capilia MAC Antibody ELISA)®)

Current Rheumatology Reviews ◽

10.2174/1573397111309020007 ◽

2013 ◽

Vol 9 (2) ◽

pp. 119-130 ◽

Cited By ~ 1

Author(s):

Maiko Watanabe ◽

Shogo Banno

Keyword(s):

Rheumatoid Arthritis ◽

Enzyme Immunoassay ◽

Pulmonary Disease ◽

Mycobacterium Avium ◽

Mycobacterium Avium Complex ◽

Nontuberculous Mycobacterium ◽

Core Antigen ◽

Mycobacterium Infections ◽

Antibody Elisa

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First line treatment selection modifies disease course and long-term clinical outcomes in Mycobacterium avium complex pulmonary disease

Scientific Reports ◽

10.1038/s41598-021-81025-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kiyoharu Fukushima ◽

Seigo Kitada ◽

Sho Komukai ◽

Tomoki Kuge ◽

Takanori Matsuki ◽

...

Keyword(s):

Pulmonary Disease ◽

Mycobacterium Avium ◽

Propensity Scores ◽

Cox Regression ◽

Line Treatment ◽

First Line ◽

Standard Regimen ◽

Cox Regression Analysis ◽

First Line Treatment

AbstractThe combination of rifamycin (RFP), ethambutol (EB), and macrolides is currently the standard regimen for treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). However, poor adherence to the standardized regimens recommended by current guidelines have been reported. We undertook a single-centred retrospective cohort study to evaluate the long-term outcomes in 295 patients with MAC-PD following first line treatment with standard (RFP, EB, clarithromycin [CAM]) or alternative (EB and CAM with or without fluoroquinolones (FQs) or RFP, CAM, and FQs) regimens. In this cohort, 80.7% were treated with standard regimens and 19.3% were treated with alternative regimens. After heterogeneity was statistically corrected using propensity scores, outcomes were superior in patients treated with standard regimens. Furthermore, alternative regimens were significantly and independently associated with sputum non-conversion, treatment failure and emergence of CAM resistance. Multivariate cox regression analysis revealed that older age, male, old tuberculosis, diabetes mellitus, higher C-reactive protein, and cavity were positively associated with mortality, while higher body mass index and M. avium infection were negatively associated with mortality. These data suggest that, although different combination regimens are not associated with mortality, first line administration of a standard RFP + EB + macrolide regimen offers the best chance of preventing disease progression in MAC-PD patients.

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