Evaluation of a bovine antibody test for diagnosing<i>Mycobacterium avium</i>complex in patients with cystic fibrosis

Qvist, Tavs; Pressler, Tacjana; Katzenstein, Terese L.; Høiby, Niels; Collins, Michael T.

doi:10.1002/ppul.23608

Cited by 6 publications

(8 citation statements)

References 22 publications

(27 reference statements)

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“…This might be an inherent weakness of the test or represent the poorly understood pathogen-host interaction of the MAC pulmonary disease spectrum, which seems to range from transient colonization to invasive disease. While the consequences of identifying subclinical MAC infection are not well understood, our results are comparable to the findings we have published using a commercial IgG ELISA designed for diagnosis of latent Johne's Disease in Cattle, a disease which resembles Crohn's disease in humans [21,26]. Although MAC and M. avium spp.…”

Section: Discussionsupporting

confidence: 84%

See 1 more Smart Citation

Antibody response against Mycobacterium avium complex in cystic fibrosis patients measured by a novel IgG ELISA test

Ravnholt

Qvist

Kolpen

et al. 2019

Journal of Cystic Fibrosis

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Background: Early signs of Mycobacterium avium complex pulmonary disease can be missed in patients with cystic fibrosis due to subclinical infection or delays in mycobacterial culture. The aim of this study was to determine the diagnostic accuracy of a novel enzyme linked immunosorbent assay for immunoglobulin G against Mycobacterium avium complex, which could help stratify patients according to risk. Methods: A retrospective cross sectional analysis of serum samples from the Copenhagen Cystic Fibrosis Center was performed. Corresponding clinical data were reviewed and patients with cystic fibrosis were assigned to one of four groups based on their mycobacterial culture results. In addition, anti-Mycobacterium avium complex immunoglobulin G levels were measured longitudinally before and after first positive culture in the period 1984-2015. Results: Three-hundred and five patients with cystic fibrosis were included with a median of five nontuberculous mycobacterial cultures. Four individuals had Mycobacterium avium complex pulmonary disease at the time of cross sectional testing and their median antibody level was 22-fold higher than patients with no history of infection (1820 vs. 80 IgG units; p b 0.001). Test sensitivity was 100% (95% CI 40-100) and specificity 77% (95% CI 72-81). Longitudinal kinetics showed rising antibodies prior to first positive culture suggesting diagnostic delay. Conclusions: Antibody screening for Mycobacterium avium complex may be used as a supplement to culture. Although confirmation in a larger cohort is needed, our findings suggest that stratifying a cystic fibrosis population into high-and low-risk groups based on antibody levels may help clinicians identify patients in need of more frequent culture.

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Section: Discussionsupporting

confidence: 84%

“…In CF research, serodiagnosis for nontuberculous mycobacteria (NTM) has previously been examined using a BCG based antigen A60 [18,19] and recently by our group in patients with Mycobacterium abscessus complex (MABSC) [20] and in patients with Mycobacterium avium spp. paratuberculosis [21]. As M. avium spp.…”

Section: Introductionmentioning

confidence: 99%

Antibody response against Mycobacterium avium complex in cystic fibrosis patients measured by a novel IgG ELISA test

Ravnholt

Qvist

Kolpen

et al. 2019

Journal of Cystic Fibrosis

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“…Nontuberculous mycobacterial (NTM) infection, currently diagnosed by culture of sputum or bronchoalveolar lavage fluid, can lead to accelerated pulmonary function decline and morbidity in CF. A commercial bovine enzyme‐linked immunosorbent assay (ELISA) for investigating antibody activity against mycobacterium avium complex (MAC) was studied in 286 patients at the Copenhagen Cystic Fibrosis Center who had a culture performed for NTM . The test, used in veterinary medicine, was modified for human use and applied to patient.…”

Section: Infectionmentioning

confidence: 99%

Cystic fibrosis year in review 2017

Savant

McColley

2018

Pediatric Pulmonology

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“…We have previously shown that serum anti-MABSC IgG antibodies rise before and during clinical infection and can be used for diagnosis, although their protective capacity is unclear, which is also the case in P. aeruginosa infection. In some cases, MABSC IgG rose several months or years before MABSC isolation in culture ( Qvist et al., 2015b ), indicating latent or subclinical infection, which is well-known to be the case for Mycobacterium tuberculosis ( Oh et al., 2020 ), and was also the seen in CF patients with MAC infection ( Qvist et al., 2017 ; Ravnholt et al., 2019 ). We also found cross-reactivity between MABSC and other NTM when measuring either anti-MABSC or anti-MAC serum IgG ( Qvist et al., 2017 ; Ravnholt et al., 2019 ), in accordance with the genetic relatedness of NTM species ( Pereira et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…In some cases, MABSC IgG rose several months or years before MABSC isolation in culture ( Qvist et al., 2015b ), indicating latent or subclinical infection, which is well-known to be the case for Mycobacterium tuberculosis ( Oh et al., 2020 ), and was also the seen in CF patients with MAC infection ( Qvist et al., 2017 ; Ravnholt et al., 2019 ). We also found cross-reactivity between MABSC and other NTM when measuring either anti-MABSC or anti-MAC serum IgG ( Qvist et al., 2017 ; Ravnholt et al., 2019 ), in accordance with the genetic relatedness of NTM species ( Pereira et al., 2020 ). Interestingly, a study showed that both the presence of Mycobacterium tuberculosis infection and the Bacillus Calmette-Guérin (BCG) vaccine (composed of an inactivated Mycobacterium bovis strain), induced cross-reactive lymphocyte response against MABSC and MAC in mice and humans ( Abate et al., 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Adaptive Immune Response to Mycobacterium abscessus Complex (MABSC) in Cystic Fibrosis and the Implications of Cross-Reactivity

Mauch

Jensen

Qvist

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundWe aimed to characterise the adaptive immune response to Mycobacterium abscessus complex (MABSC) and its cross-reactivity with Mycobacterium avium complex (MAC) and Mycobacterium bovis (Bacille Calmette-Guérin, BCG) in cystic fibrosis (CF) patients and non-CF controls in terms of lymphocyte proliferation and immunophenotyping, cytokine production and anti-MABSC IgG plasma levels.MethodsIn this cross-sectional analysis, peripheral blood mononuclear cells (PBMC) from CF patients with MABSC (CF/MABSC, n=12), MAC infection history (CF/MAC, n=5), no NTM history (CF/NTM-, n=15), BCG-vaccinated (C/BCG+, n=9) and non-vaccinated controls (C/BCG-, n=8) were cultured for four days under stimulation with an in-house MABSC lysate and we used flow cytometry to assess lymphocyte proliferation (given by lymphoblast formation) and immunophenotypes. Cytokine production was assessed after overnight whole blood stimulation with the same lysate, and anti-MABSC IgG levels were measured in plasma from non-stimulated blood.ResultsAll CF/MABSC patients had increased CD3+ and CD19+ lymphoblast formation upon PBMC stimulation with MABSC lysate. There was a higher rate of CD3+ than CD19+ lymphoblasts, predominance of CD4+ over CD8+ lymphoblasts, IFN-γ, TNF-α and IL-2 production, low production of the Th17-associated IL-17, and discrete or no production of Th2/B cell-associated cytokines soluble CD40 ligand (CD40L), IL-4 and IL-5, indicating a Th1-dominated phenotype and infection restricted to the lungs. A similar pattern was seen in C/BCG+ controls, and CF/MAC patients, pointing to cross-reactivity. MABSC-IgG levels were higher in CF/MABSC patients than in both control groups, but not CF/NTM- patients, most of whom also had CD3+ and/or CD19+ lymphoblast formation upon PBMC stimulation, indicating previous exposure, subclinical or latent infection with MABSC or other NTM.ConclusionThe anti-MABSC immune response is Th1-skewed and underlines the cross-reactivity in the anti-mycobacterial immune response. The results, together with published clinical observations, indicate that BCG vaccination may cross-react against NTM in CF patients, and this should be investigated. Due to cross-reactivity, it would also be interesting to investigate whether a combination of MABSC-induced cytokine production by blood cells and anti-MABSC IgG measurement can be useful for identifying latent or subclinical infection both with MABSC and other NTM in CF patients.

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Evaluation of a bovine antibody test for diagnosingMycobacterium aviumcomplex in patients with cystic fibrosis

Cited by 6 publications

References 22 publications

Antibody response against Mycobacterium avium complex in cystic fibrosis patients measured by a novel IgG ELISA test

Antibody response against Mycobacterium avium complex in cystic fibrosis patients measured by a novel IgG ELISA test

Cystic fibrosis year in review 2017

Adaptive Immune Response to Mycobacterium abscessus Complex (MABSC) in Cystic Fibrosis and the Implications of Cross-Reactivity

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