Diagnosis Of Mycobacterium Avium Complex Pulmonary Disease Research Articles

Evaluation of plasma anti-GPL-core IgA and IgG for diagnosis of disseminated non-tuberculous mycobacteria infection.

Detection of IgA antibody against Mycobacterium avium complex (MAC) glycopeptidolipid (GPL) has recently been shown to improve the diagnosis of MAC pulmonary disease but has yet to be tested in disseminated Non-tuberculous mycobacteria (NTM) infection. In this study, we address the diagnostic efficacies of an anti-GPL-core ELISA kit in disseminated lymphadenopathy patients positive for NTM culture and anti-IFN-γ autoantibodies. The study was conducted in a tertiary referral center in northeastern Thailand and patients with NTM, tuberculosis, melioidosis, and control subjects were enrolled. Plasma immunoglobulin A (IgA) and G (IgG) antibodies against GPL-core were detected in the subjects and the specificity and sensitivity of the assay was assessed. Anti-GPL-core IgA and IgG levels were significantly higher in NTM patients than other groups (p < 0.0001). Diagnostic efficacy for NTM patients using anti-GPL-core IgA cut-off value of 0.352 U/ml showed good sensitivity (91.18%) and intermediate specificity (70.15%). Using a cut-off value of 4.140 AU/ml for anti-GPL-core IgG showed the same sensitivity (91.18%) with increased specificity (89.55%) and an 81.58% positive predictive value. Most patients with moderate levels (4.140-7.955 AU/ml) of anti-GPL-core IgG had rapidly growing mycobacteria (RGM) infection. Taken together, the detection of anti-GPL-core antibodies could provide a novel option for the diagnosis and management of disseminated NTM infected patients.

Application of a commercial serodiagnostic kit that measures the serum anti-glycopeptidolipid core IgA antibody in Mycobacterium avium complex pulmonary disease.

The diagnosis of Mycobacterium avium complex (MAC) pulmonary disease is occasionally cumbersome and time-consuming because the MAC species is ubiquitous, and therefore its detection is not necessarily indicative of a definitive diagnosis. A serodiagnostic method specific for MAC pulmonary disease that measures the serum anti-glycopeptidolipid core antigen IgA has been developed and is commercially available. Meta-analysis revealed that the test showed a good diagnostic accuracy. The estimated sensitivity and specificity values were 69.6% (95% confidence interval 62.1-76.1) and 90.6% (95% confidence interval 83.6-95.1), respectively. As antibody levels may reflect the disease activity, their serial measurement can also be used in the management of MAC disease. To justify its routine use in clinical practice, further validation in various regions and studies addressing whether serodiagnosis combined with present diagnostic criteria facilitate more rapid accurate diagnosis of MAC pulmonary disease are necessary.

Low body mass index and lymphocytopenia associate with Mycobacterium avium complex pulmonary disease in patients with rheumatoid arthritis

Objectives: Patients with rheumatoid arthritis (RA) are at an increased risk of Mycobacterium avium complex pulmonary disease (MAC-PD). We aimed to identify factors associated with MAC-PD in RA patients, and investigate their clinical significance for diagnosis of this disease.Methods: We examined 396 patients with RA for the presence of MAC-PD, using the criteria of the American Thoracic Society and conducted three years of follow-up on these patients. Multivariate logistic analyses were employed for selecting factors associated with MAC-PD. We developed a point system based on these factors which we call MAC-PD score to improve diagnosis of MAC-PD.Results: During this study, 14 out of 396 patients were newly diagnosed with MAC-PD. Multivariate analyses revealed body mass index (BMI) <18.0 kg/m2 and lymphocyte count <1500/μl were associated with MAC-PD in RA patients. Points were assigned to them and totalled to provide the MAC-PD score. Among 20 patients with high-resolution computer tomography images consistent with MAC-PD, the scores were significantly higher in 14 patients with MAC-PD than those in six patients without MAC-PD.Conclusion: Using these data, in the forms of the MAC-PD score, could help to identify patients who should be considered for bronchoscopy more selectively.

Hsa-miR-346 is a potential serum biomarker of Mycobacterium avium complex pulmonary disease activity.

MicroRNA (miRNA) has been recently recognized as a biomarker of various diseases; however, there are no known miRNAs associated with Mycobacterium avium complex (MAC) pulmonary disease. In addition, there are no known biomarkers to precisely reflect disease activity after the diagnosis of MAC pulmonary disease. Thus, we sought to identify a miRNA which is a candidate biomarker of MAC pulmonary disease activity. Serum hsa-miR-346 concentrations of 16 patients with M.avium pulmonary disease were significantly higher than those of 16 healthy controls (p=0.047). The secretion of hsa-miR-346 increased in a multiplicity of infection-dependent manner in M.avium-infected macrophages. Serum hsa-miR-346 levels of 5 patients with bacterial conversion at the end of follow-up were significantly lower than those at the beginning of the follow-up (p=0.043). In addition, the longitudinal change in serum hsa-miR-346 concentration correlated with bacterial load in 2 patients with M.avium pulmonary disease. Based on our results, it is supposed that MAC-infected macrophages in pulmonary lesions produce hsa-miR-346, which is then secreted into the bloodstream. The magnitude of this process could be quantitatively controlled by the bacterial load, suggesting that serum hsa-miR-346 is a potentially useful biomarker of MAC pulmonary disease activity.

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.

Serodiagnostic Contributions of Antibody Titers against Mycobacterial Lipid Antigens inMycobacterium aviumComplex Pulmonary Disease

Although the incidence of pulmonary tuberculosis is decreasing, the number of immunocompetent patients with Mycobacterium avium complex (MAC) pulmonary disease is steadily increasing. Therefore, albeit not contagious, MAC pulmonary disease needs to be diagnosed rapidly and accurately. We examined the serodiagnostic contributions of serum immunoglobulin G antibody titers against the species-specific and -common mycobacterial lipid antigens in the diagnosis of MAC pulmonary disease. Serum samples were obtained from 65 patients with MAC pulmonary disease, 15 patients with suspected MAC disease, 25 patients with pulmonary tuberculosis, 10 patients with Mycobacterium kansasii disease, and 100 healthy volunteers (control subjects). We measured the serum immunoglobulin G antibody titers against trehalose monomycolate (TMM-M) and apolar-glycopeptidolipid (GPL), lipid antigens extracted from MAC. In patients with MAC pulmonary disease, the antibody titers against TMM-M and apolar-GPL were significantly higher than those in the other patient groups or in the control subjects. By receiver operator characteristic curve analysis, an optical density of 0.27, corresponding to the optimal cutoff antibody titer against TMM-M, was associated with a sensitivity of 89.2% and a specificity of 97.0%, and an optical density of 0.33, corresponding to the optimal cutoff antibody titer against apolar-GPL, was associated with a sensitivity of 89.2% and a specificity of 94.0%. Measurements of antibody titers against TMM-M and apolar-GPL would be useful in the diagnosis of MAC pulmonary disease and in the differential diagnosis of mycobacterial pulmonary disease.

The significance of bronchoscopy for the diagnosis of Mycobacterium avium complex (MAC) pulmonary disease.

To investigate the usefulness of bronchoscopy for the diagnosis of Mycobacterium avium complex (MAC) pulmonary disease, we retrospectively reviewed the clinical charts, and radiographic and bacteriologic findings of all patients who were admitted to our hospital between 1994 and 2000, and who fulfilled the 1997 American Thoracic Society (ATS) criteria for MAC pulmonary infection. A total of 132 patients were diagnosed as affected by MAC pulmonary disease during that period. Of these, bronchoscopic examination was performed in those patients who showed negative sputum smear for mycobacteria on three consecutive days (n = 43) or who could not expectorate sputum (n = 2). Of 42 patients, sputum culture was positive for MAC in 34 patients (81.0%). Bronchial washing sample was smear-positive for MAC in 17 of 39 patients (43.6%), and culture-positive for MAC in 33 of the 39 patients (84.6%). Transbronchial lung biopsy (TBLB) specimens revealed specific findings (epithelioid cell granuloma and/or acid-fast bacilli) in 14 of 38 patients (36.9%). Bronchial washing of all patients who showed specific histology in TBLB grew MAC in culture. Based on the bronchoscopic examination, we could diagnose MAC pulmonary disease in 36 patients. In addition, smear and polymerase chain reaction (PCR) results of bronchial washing made possible an early diagnosis of MAC pulmonary disease in 15 patients. We examined the relation of CT findings to bronchial washing results. Isolation of MAC in bronchial washing is significantly related to small nodular opacity around the ectatic bronchi on the CT scan (p = 0.016). In our retrospective study, in sputum smear-negative patients with MAC pulmonary disease, MAC isolation by culture of bronchial washing was no more frequent than that with sputum culture. However, bronchial washing is useful to differentiate infection from casual isolation of MAC. In addition, we could make early diagnosis of MAC pulmonary disease based on smear and PCR results of bronchial washing. To make a diagnosis of MAC, bronchial washing is superior to TBLB, and should be done in the bronchus which drains the area revealing small nodular opacity around ectatic bronchi.