Serological biomarkers for the diagnosis of Mycobacterium abscessus infections in cystic fibrosis patients

Moigne, Vincent Le; Roux, Anne-Laure; Mahoudo, Hélène; Christien, G; Ferroni, Agnès; Dumitrescu, Oana; Lina, Gérard; Bouchara, Jean‐Philippe; Plésiat, Patrick; Gaillard, Jean‐Louis; Canaan, Stéphane; Héry-Arnaud, Geneviève; Herrmann, Jean-Louis

doi:10.1016/j.jcf.2021.08.019

Cited by 7 publications

(18 citation statements)

References 42 publications

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“…As mentioned, mycobacteria share a number of antigens that may trigger both T and B cell responses ( Checkley et al., 2011 ; Qvist et al., 2015b ; Qvist et al., 2017 ; Ravnholt et al., 2019 ), which has also been shown in a recent study using four MABSC antigens and two recombinant proteins ( Le Moigne et al., 2021 ). As our in-house MABSC lysate is produced by means of X-press and sonication ( Closs et al., 1980 ), it contains common mycobacterial antigens ( Høiby et al., 1987 ; Qvist et al., 2015b ), allowing us to measure a broader immune response to environmental NTM.…”

Section: Discussionmentioning

confidence: 53%

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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Section: Discussionmentioning

confidence: 53%

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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“…In addition, this multi-antigen analysis gives even better results when IgG and IgA levels are cumulated, like improving sensitivity from 23% to 62% as described by Juliàn et al ( 23 ) for M. tuberculosis . Introducing the IgG results obtained from the same cohort ( 17 ) allowed us to see that when at least three results are positive, we obtained a sensitivity of 60.6%, a specificity of 95.3% and positive and negative predictive values of 32.6% and 98.5%, respectively (Table S4). Similarly, these sensitivity values can reach 90% if at least one of the tests is positive i.e., either IgA with TLR2e, or IgA with rPLC and likewise IgG (Table S4).…”

Section: Discussionmentioning

confidence: 99%

“…Serum samples for antibody determination, antigens, or preparations used in this study as well as the distribution of the different groups depending on the results of sputum cultures are the same as those previously described ( 17 ).…”

Section: Methodsmentioning

confidence: 99%

“…ELISAs were developed as described previously ( 17 ). First, the coating of plates was completed overnight at 4°C with 1 μg/mL of each antigen, recombinant PLC (rPLC), or the surface-extract TLR2 activators-enriched fraction (TLR2eF) diluted in 100 μL of carbonate-bicarbonate buffer (0.1 M, pH 9.6).…”

Section: Methodsmentioning

confidence: 99%

“…As part of a diagnostic accuracy study, we demonstrate the importance of IgG antibodies detection for the diagnosis of NTM infections in CF patients, and more accurately for those infected by M. abscessus infections with two antigenic preparations ( 17 ). Using the same serum collection and the same antigens, we evaluated the potential of the IgA detection technique in enhancing the diagnosis of NTM infections, in order to decipher a more complete humoral response in CF patients infected by NTM, and to see if the IgA response might be a new diagnostic tool for detecting NTM-infected CF patients, and more specifically M. abscessus - infected CF patients.…”

Section: Introductionmentioning

confidence: 90%

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IgA Serological Response for the Diagnosis of Mycobacterium abscessus Infections in Patients with Cystic Fibrosis

et al. 2022

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Nontuberculous Mycobacteria in Cystic Fibrosis in the Era of Cystic Fibrosis Transmembrane Regulator Modulators

Burke

Thomson

Wainwright

et al. 2023

Semin Respir Crit Care Med

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Nontuberculous mycobacteria (NTM) are a group of mycobacteria which represent opportunistic pathogens that are of increasing concern in people with cystic fibrosis (pwCF). The acquisition has been traditionally though to be from environmental sources, though recent work has suggested clustered clonal infections do occur and transmission potential demonstrated among pwCF attending CF specialist centers. Guidelines for the screening, diagnosis, and identification of NTM and management of pwCF have been published. The emergence of CF-specific therapies, in particular cystic fibrosis transmembrane regulator (CFTR) modulator drugs, have led to significant improvement in the health and well-being of pwCF and may lead to challenges in sampling the lower respiratory tract including to screen for NTM. This review highlights the epidemiology, modes of acquisition, screening and diagnosis, therapeutic approaches in the context of improved clinical status for pwCF, and the clinical application of CFTR modulator therapies.

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Serological biomarkers for the diagnosis of Mycobacterium abscessus infections in cystic fibrosis patients

Cited by 7 publications

References 42 publications

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

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

IgA Serological Response for the Diagnosis of Mycobacterium abscessus Infections in Patients with Cystic Fibrosis

Nontuberculous Mycobacteria in Cystic Fibrosis in the Era of Cystic Fibrosis Transmembrane Regulator Modulators

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