Glycopeptidolipid Core Research Articles

Serum GPL core antibody levels are associated with disease activity and treatment outcomes in Mycobacterium avium complex lung disease following first line antibiotic treatment

BackgroundNo objective serum biomarkers of disease course or treatment outcome of Mycobacterium avium complex lung disease (MAC-LD) presently exist. Serum IgA antibody levels against the glycopeptidolipid (GPL) core have good diagnostic accuracy for MAC-LD. However, their usefulness for monitoring and predicting disease course and outcome of MAC-LD following first-line antibiotic treatment remains unclear. MethodsWe conducted a single-center retrospective cohort study to investigate the utility of serial measurements of GPL core IgA antibodies for monitoring disease course in 133 patients with MAC-LD following first-line antibiotic treatment. ResultsPatients were classified into treatment failure [n = 46 (34.6%)], recurrence [n = 19 (14.3%)], or treatment success [n = 68 (51.1%)] groups according to bacteriological outcomes after chemotherapy. Pretreatment serum anti-GPL core IgA levels in the treatment success group were similar to those in the treatment failure and recurrence groups (P = 0.6431 and P = 0.9045, respectively). In the treatment success group, serum anti-GPL core IgA levels were significantly and continuously reduced after initiating antibiotic treatment. No significant reductions in anti-GPL core IgA levels were observed in either the treatment failure or recurrence groups. Reduced levels of GPL core antibodies following antibiotic treatment correlated well with treatment outcomes (P = 0.0045). ConclusionIn this study, by performing serial measurements, we found that GPL core antibody levels were associated with disease activity and treatment outcomes in patients with MAC-LD. Time course analysis of anti-GPL core IgA levels clearly differentiated between patients who achieved treatment success and those who experienced treatment failure or disease recurrence.

Serological diagnosis of Mycobacterium avium complex lung diseases by enzyme immunoassay of IgA antibodies against MAC-specific glycopeptidolipid core antigen

IntroductionThere is an increasing trend worldwide in the incidence of Mycobacterium avium complex pulmonary diseases (MAC-PD) and the diagnosis is sometimes complicated. Recently, an enzyme immunoassay (EIA) kit that detects serum IgA antibody against MAC-specific glycopeptidolipid (GPL) core antigen had been developed and found to be useful in discriminating MAC-PD from other lung diseases. The antibody was subsequently also found to be elevated in patients suffering Mycobacterium abscessus pulmonary diseases (MAB-PD). This study is to evaluate this EIA kit in the serological diagnosis of MAC-PD in Hong Kong Chinese patients. MethodsThe study was conducted in Grantham Hospital, Hong Kong between July 2017 and July 2018. Assay of the IgA antibody level using the EIA kit was done on blood samples collected from patients suffering from MAC-PD, MAB-PD, pulmonary tuberculosis and other lung diseases. ResultsThere were 100 subjects recruited into the study, among which 11 were excluded. By using the cut-off value 0.7 U/mL provided by the manufacturer, the sensitivity and specificity for diagnosis were 73.7% and 77.6% for MAC-PD; 50% and 77.6% for MAB-PD. By receiver operating characteristic curves analysis, new cut-off for MAC-PD and MAB-PD were calculated as 1.771 U/mL and 0.172 U/m, respectively. The sensitivity and specificity were 68.4% and 86.2% for MAC-PD, whereas 66.7% and 72.4% for MAB-PD. ConclusionsOur study showed that the enzyme immunoassay of IgA antibodies against MAC-specific glycopeptidolipid core antigen could help to distinguishing MAC and M. abscessus pulmonary diseases from pulmonary tuberculosis and other lung diseases among Hong Kong Chinese patients. Further larger scale studies in our local population for the usefulness of this antibody test in the diagnosis and monitoring of MAC and M. abscessus lung diseases might be warranted.

The impact of adjuvant surgical treatment of nontuberculous mycobacterial pulmonary disease on prognosis and outcome

BackgroundLung resection in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) has been reported to be associated with favorable outcomes. However, little is known regarding the risk and prognostic factors for refractory and recurrent cases. We aimed to evaluate the overall impact and benefit of adjuvant lung surgery by comparing NTM-PD patients who underwent adjuvant lung resection with those treated exclusively with antibiotics. We also investigated the efficacy of serum IgA antibody against glycopeptidolipid (GPL) core antigen (GPL core antibody) to monitor disease activity and predict the recurrence of disease after adjuvant lung resection.MethodsWe retrospectively evaluated the clinical characteristics and surgical outcomes of 35 patients surgically treated for NTM-PD. Furthermore, we compared surgically treated patients and control patients treated exclusively with antibiotics who were matched statistically 1:1 using a propensity score calculated from age, sex, body mass index, and radiologic features of disease.ResultsIn the surgically treated patients, the median age was 58 (interquartile range, 47–65) years and 65.7% were female. Twenty-eight patients had Mycobacterium avium complex. Operations comprised four pneumonectomies, two bilobectomies, one bilobectomy plus segmentectomy, 17 lobectomies, two segmentectomies, and nine lobectomies plus segmentectomies. Postoperative complications occurred in seven patients (20%), there were no operative deaths, and 33 (94.3%) patients achieved negative sputum culture conversion. Refractory and recurrent cases were associated with remnant bronchiectasis, contralateral shadows, and positive acid-fast bacilli staining or culture. Of 28 statistically matched pairs, long-term sustained negative culture conversion was observed in 23 (82.2%) surgical group patients and in 14 (50.0%) non-surgical group patients (0.0438). The mortality rate was lower in the surgical group, but did not reach statistical significance (one in the surgical group and four in the non-surgical group, p = 0.3516). GPL core antibody was correlated with disease activity and recurrence.ConclusionsNTM-PD patients who underwent adjuvant lung resection experienced overall favorable outcomes and achieved sputum culture conversion more frequently. Long-term mortality may have been reduced by this procedure, and the level of GPL core antibody was shown to be a good clinical indicator of disease activity after surgery.

Serum immunoglobulin a antibodies to glycopeptidolipid core antigen for Mycobacteroides abscessus complex lung disease.

Mycobacteroides abscessus complex (MABC) exhibits smooth morphotypes, expressing glycopeptidolipid (GPL), and rough morphotypes, expressing diminished GPL, on the MABC cell wall. Few reports have focused on the relationship between anti-GPL-core immunoglobulin A (IgA) antibody and colony morphology in MABC lung disease. This study aimed to test GPL core antigen in patients with MABC lung disease to investigate the relationship between coinfection/contamination in other nontuberculous mycobacteria species and colony morphology variant in MABC isolates. Patients with MABC lung disease and contamination diagnosed between 2012 and 2017 at our hospital were enrolled retrospectively. Of the assessed patients, 43 patients with MABC lung disease and 13 with MABC contamination were included. There was a significant difference in anti-GPL-core IgA antibody levels between them (P = 0.02). Forty-three patients with MABC lung disease were divided into two groups as positive and negative antibodies groups. A significant increase in the positive anti-GPL-core IgA antibody was observed in coexistence with both Mycobacterium avium complex (MAC) (P = 0.02) and the isolate of the smooth variant (P = 0.03) in MABC. Anti-GPL-core IgA antibodies in patients with MABC are greatly influenced by MAC coexistence, and colony morphology variant of the MABC isolate.

Changes in Serum IgA Antibody Levels against the Glycopeptidolipid Core Antigen during Antibiotic Treatment of Mycobacterium avium Complex Lung Disease.

We evaluated serial changes in the levels of serum immunoglobulin A (IgA) antibody to the glycopeptidolipid (GPL) core antigen during antibiotic treatment in 57 patients with Mycobacterium avium complex (MAC) lung disease at baseline (T0) and after 3 months (T3) and 6 months (T6) of treatment. The median patient age was 59 years, and 37 (65%) patients were women. The etiologic organisms included M. avium in 32 (56%) patients and M. intracellulare in 25 (44%) patients. Seven (12%) patients had the fibrocavitary form of the disease on computed tomography. After 12 months of treatment, 42 (74%) patients had a favorable response to treatment, whereas 15 (26%) patients had an unfavorable response to treatment defined as the absence of sputum culture conversion within 12 months of treatment. The initial median serum anti-GPL IgA levels in the 57 patients was 3.50 U/mL, and the antibody levels at T0 (median 3.50 U/mL), T3 (median 2.71 U/mL), and T6 (median 2.61 U/mL) were significantly decreased following treatment (P ＜ 0.001). The results of the multivariate analysis indicated that an initially elevated anti-GPL IgA level (＞ 3.50 U/mL) was associated with an unfavorable response (P = 0.049). Our data suggest that elevated anti-GPL IgA levels may reflect disease activity and may help predict treatment response in patients with MAC lung disease.

Diagnostic performance of measuring antibodies to the glycopeptidolipid core antigen specific to Mycobacterium avium complex in patients with rheumatoid arthritis: results from a cross-sectional observational study.

IntroductionThe aim of this study was to investigate the diagnostic performance of measuring antibodies to the glycopeptidolipid (GPL) core antigen specific to Mycobacterium avium complex (MAC) in patients with rheumatoid arthritis (RA).MethodsWe cross-sectionally investigated anti-GPL antibodies and radiographs of 396 patients with RA. A diagnosis of MAC pulmonary disease (MAC-PD) was made according to the criteria by the American Thoracic Society and the Infectious Diseases Society of America. Serum immunoglobulin A antibodies to MAC-specific GPL core antigen were measured by an enzyme immunoassay. All patients with RA with abnormal shadows on chest x-rays underwent chest computed tomography (CT). Bronchoscopy was performed on patients with negative cultures for MAC by expectorated sputum and positive CT findings compatible with MAC-PD.ResultsTen patients were newly diagnosed with MAC-PD. Eight individuals who already had diagnoses of MAC-PD at the time of enrollment and nineteen who had negative expectorated sputum cultures for MAC and positive CT images compatible with MAC-PD and who refused bronchoscopy were excluded from the following analysis. Anti-GPL antibodies were detected in 12 of 369 patients. Eight of the ten patients with MAC-PD and 4 of 359 patients without MAC-PD tested positive for the anti-GPL antibodies. The specificity and sensitivity were 99 % and 80 %, respectively. Positive and negative predictive values were 67 %, and 97 %, respectively. When we analyzed diagnostic performance of the antibodies in 57 patients with RA who had abnormal shadows on chest x-rays, the positive and negative predictive values were 100 %, and 96 %, respectively. Twelve patients underwent bronchoscopy. Bronchoalveolar lavage fluid (BALF) samples from six patients were positive for MAC, and BALF samples from the remainder were negative. Anti-GPL antibodies were detected in the sera of all six patients with positive results for MAC by BALF sampling, whereas the antibodies were not detected in the sera from the remainder with negative results for MAC by BALF sampling.ConclusionsThe measurement of anti-GPL antibodies is useful as a supplementary diagnostic tool for MAC-PD in patients with RA and may provide a new strategy, in combination with chest x-ray and CT, for differentiating MAC-PD from other pulmonary comorbidities in patients with RA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0787-y) contains supplementary material, which is available to authorized users.

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)®.

Nontuberculous mycobacteria (NTM) are ubiquitous environmental organisms that can cause various diseases, including pulmonary disease (PD). In patients with rheumatoid arthritis (RA), numerous pulmonary manifestations, including bronchiectasis, may develop into Mycobacterium avium-complex (MAC)-PD, which can be lethal in patients who are being treated with a tumor necrosis factor-alpha blocker. However, the bronchiectasis associated with NTM-PD is difficult to distinguish from that associated with RA by radiological imaging alone. In addition, the diagnosis of NTM-PD is often hampered by the ease of NTM contamination. For the serological diagnosis of MAC-PD, the enzyme immunoassay (EIA) kit, Capilia MAC Antibody ELISA®, determines the levels of serum IgA antibody to the glycopeptidolipid core of MAC. Here we describe the efficacy of this EIA kit for diagnosing MAC-PD, and we review the characteristics of NTM and the association between RA patients and NTM infections.

Serodiagnosis of Mycobacterium avium Complex and Mycobacterium abscessus Complex Pulmonary Disease by Use of IgA Antibodies to Glycopeptidolipid Core Antigen

An enzyme immunoassay kit that detects serum IgA antibody reacting to glycopeptidolipid core antigen derived from Mycobacterium avium complex (MAC) was not useful for differentiating MAC pulmonary disease (PD) from Mycobacterium abscessus complex PD (MAB-PD). However, this assay could be useful for differentiating MAC- and MAB-PD from pulmonary tuberculosis. (This study has been registered at ClinicalTrials.gov under registration no. NCT00970801.).

Serological assay by use of glycopeptidolipid core antigen for Mycobacterium avium complex

We evaluated the clinical usefulness of glycopeptidolipid (GPL) core antigen for diagnosing Mycobacterium avium complex (MAC) pulmonary disease (MAC-PD), including patients with clinically suspected MAC-PD. GPL core antibody levels were measured in 57 patients with MAC-PD satisfying the American Thoracic Society (ATS) criteria for pulmonary disease due to non-tuberculous mycobacteria (NTM), and in 18 patients with clinically suspected MAC-PD, 10 with MAC contamination, 18 with pulmonary tuberculosis (TB), 9 with other NTM disease, 18 with other lung diseases, and 20 healthy subjects. The positive response rate was 77% for MAC-PD, 39% for suspected MAC-PD, 10% for MAC contamination, and 0% for pulmonary TB, other NTM diseases, other lung diseases, and healthy subjects. GPL core antibody levels were significantly higher in patients with MAC-PD than in those of the other groups (p < 0.01). The sensitivity and specificity of the GPL core antibody assay for MAC were 77% and 99%, respectively. Among 13 patients with MAC-PD who showed false-negative results, 5 had immunosuppressive underlying diseases. No significant correlations between the antibody level and species of MAC, clinical disease types, and extent of the disease on chest computed tomography were found in patients with MAC-PD. This enzyme immunoassay kit is a useful supportive method for the rapid and convenient diagnosis of MAC-PD using a small dose of serum, and for the differentiation of MAC-PD from other lung diseases. However, underlying diseases need to be considered in the interpretation of negative results.

Serodiagnosis ofMycobacterium aviumcomplex pulmonary disease in the USA

Diagnosis of Mycobacterium avium complex pulmonary disease (MAC-PD) can be difficult. A previous study from Japan reported the usefulness of a serodiagnostic test for MAC-PD. The objective of this study was to evaluate the usefulness of the test in similar patients in the USA. 100 patients with known or suspected MAC-PD and 52 healthy volunteers were enrolled into the study at National Jewish Health, Denver, CO, USA. Serum glycopeptidolipid core immunoglobulin A antibody levels were measured with an enzyme immunoassay (EIA) kit and routine clinical evaluations were performed. The patients were divided into two groups based on clinical evaluation: 87 patients with MAC-PD that met American Thoracic Society criteria, and 13 who did not meet the criteria. The sensitivity and specificity (cut-off point 0.3 U·mL(-1)) of the serodiagnostic test for diagnosing MAC-PD were 70.1% and 93.9%, respectively. Among the 44 patients in the MAC-PD group with two or more positive sputum cultures within the previous 6 months, sensitivity was 81.8%. The EIA kit demonstrated good sensitivity and specificity for the identification of MAC-PD, particularly in patients with two or more positive cultures, and may be useful for rapid MAC-PD diagnosis.

Serodiagnosis of Mycobacterium avium–Complex Pulmonary Disease Using an Enzyme Immunoassay Kit

The diagnosis of Mycobacterium avium-complex pulmonary disease (MAC-PD) and/or its discrimination from pulmonary tuberculosis (TB) is sometimes complicated and time consuming. We investigated in a six-institution multicenter study whether a serologic test based on an enzyme immunoassay (EIA) kit was useful for diagnosing MAC-PD and for distinguishing it from other lung diseases. An EIA kit detecting serum IgA antibody to glycopeptidolipid core antigen specific for MAC was developed. Antibody levels were measured in sera from 70 patients with MAC-PD, 18 with MAC contamination, 37 with pulmonary TB, 45 with other lung diseases, and 76 healthy subjects. Significantly higher serum IgA antibody levels were detected in patients with MAC-PD than in the other groups (P < 0.0001). Setting the cutoff point at 0.7 U/ml resulted in a sensitivity and specificity of the kit for diagnosing MAC-PD of 84.3 and 100%, respectively. Significantly higher antibody levels were also found in patients with nodular-bronchiectatic disease compared with fibrocavitary disease in MAC-PD (P < 0.05). There was a positive correlation between the extent of disease on chest computed tomography scans and the levels of antibody (r = 0.43, P < 0.05) in patients with MAC-PD. The EIA kit is useful for the rapid diagnosis of MAC-PD and for differentiating MAC-PD from pulmonary TB and, if validated by studies in other populations, could find wide application in clinical practice.

Serological test and chest computed tomography findings in patients with Mycobacterium avium complex lung disease

The present authors have previously reported the usefulness of a serodiagnostic test to detect serum glycopeptidolipid (GPL) core antibody in diagnosing Mycobacterium avium complex (MAC) lung disease in immunocompetent patients. The aim of the present study was to investigate correlations between the levels of antibody against GPL core and chest computed tomography (CCT) findings in patients with MAC lung disease. A total of 47 patients with MAC-positive culture from their sputum and who had radiographic abnormalities were investigated. Thirty-three patients met the American Thoracic Society criteria for MAC disease; 14 did not. All patients underwent both CCT examination and the serodiagnostic test for MAC at the same time. Small nodular shadows were seen on CCT in all 47 patients and bronchiectasis shadows were seen in 39 (83%) of them. There was a significant positive correlation between the extent of the disease and the level of GPL core immunoglobulin (Ig)A antibody. The levels of GPL core IgA antibody were significantly elevated in patients who had nodular shadows (10-30 mm) compared with patients who had small nodular shadows (<10 mm). The present results document that the levels of immunoglobulin A antibody against glycopeptidolipid core correlate with the chest computed tomography findings of Mycobacterium avium complex lung disease.

Use of Glycopeptidolipid Core Antigen for Serodiagnosis of Mycobacterium avium Complex Pulmonary Disease in Immunocompetent Patients

We report the development of a serodiagnostic method for Mycobacterium avium complex (MAC) disease with an enzyme immunoassay (EIA) with the MAC-specific glycopeptidolipid (GPL) core as the antigen. In this study, we confirmed by EIA that the GPL core antibody was in the sera of immunocompetent patients with MAC disease. The EIA for quantifying the GPL core antibody was evaluated as a clinical tool for serodiagnosis of pulmonary MAC disease. A significant increase in GPL core antibodies (immunoglobulins G, A, and M) was detected in sera of patients with MAC pulmonary diseases when they were compared to patients who were colonized with MAC, patients with Mycobacterium kansasii disease or tuberculosis, and healthy subjects. The sensitivities and specificities of the GPL core-based EIA for diagnosis of MAC pulmonary disease were 72.6% and 92.2%, respectively, for IgG, 92.5% and 95.1%, respectively, for IgA, and 78.3% and 91.0%, respectively, for IgM. The best sensitivity and specificity were obtained by measuring immunoglobulin A antibodies against GPL core antigen. The level of GPL core antibodies reflected disease activity, since it decreased in cured MAC patients who had responded to chemotherapy. Measurement of serum antibodies against GPL core is useful for both diagnosis and assessment of disease activity in MAC disease of the lung.