Vincent Le Moigne1, Anne-Laure Roux2, Hélène Mahoudo3, Gaëtan Christien3, Agnès Ferroni4, Oana Dumitrescu5, Gérard Lina5, Jean-Philippe Bouchara6, Patrick Plésiat7, Jean-Louis Gaillard2, Stéphane Canaan8, Geneviève Héry-Arnaud9, Jean-Louis Herrmann10. 1. Université Paris Saclay, UVSQ, Inserm, Infection et Inflammation, Montigny-le-Bretonneux, France. Electronic address: vincent.le-moigne@uvsq.fr. 2. Université Paris Saclay, UVSQ, Inserm, Infection et Inflammation, Montigny-le-Bretonneux, France; AP-HP, GHU Paris Saclay, Hôpital Ambroise Paré, Service de Microbiologie, Boulogne-Billancourt, France. 3. Université Paris Saclay, UVSQ, Inserm, Infection et Inflammation, Montigny-le-Bretonneux, France. 4. AP-HP, GHU Paris, Hôpital Necker-Enfants Malades, Service de Microbiologie, Paris 15e, France. 5. Hospices Civils de Lyon, Hôpital de la Croix Rousse-Centre de Biologie Nord, Institut des Agents Infectieux, Laboratoire de Bactériologie, Grande Rue de la Croix Rousse, 69004, Lyon, France; Centre International de Recherche en Infectiologie, INSERM U1111, Université de Lyon, Lyon, France. 6. CHU, Service de Parasitologie-Mycologie, Groupe d'Etude des Interactions Hôte-Pathogène (GEIHP, EA 3142), UNIV Angers, UNIV Brest, SFR 4208 ICAT, Angers, France. 7. Laboratoire de Bactériologie, CHRU de Besançon, UMR CNRS 6249 Chrono-Environnement, Faculté de Médecine-Pharmacie, Université de Bourgogne Franche-Comté, Besançon, France. 8. Université Aix-Marseille, CNRS, LISM, IMM FR3479, Marseille, France. 9. Département de bactériologie-virologie, hygiène et parasitologie-mycologie, centre hospitalier régional universitaire (CHRU) de Brest, Brest, France; Inserm, EFS, UMR 1078 France « génétique, génomique fonctionnelle et biotechnologies », GGB, université Brest, 29200 Brest, France. 10. Université Paris Saclay, UVSQ, Inserm, Infection et Inflammation, Montigny-le-Bretonneux, France; AP-HP, GHU Paris Saclay, Hôpital Raymond Poincaré, Service de Microbiologie, Garches, France. Electronic address: jean-louis.herrmann@aphp.fr.
Abstract
BACKGROUND: Culture conditions sometimes make it difficult to detect non-tuberculous mycobacteria (NTM), particularly Mycobacterium abscessus, an emerging cystic fibrosis (CF) pathogen. The diagnosis of NTM positive cases not detected by classical culture methods might benefit from the development of a serological assay. METHODS: As part of a diagnostic accuracy study, a total of 173 sera CF-patients, including 33 patients with M. abscessus positive cultures, and 31 non-CF healthy controls (HC) were evaluated. Four M. abscessus antigens were used separately, comprising two surface extracts (Interphase (INP) and a TLR2 positive extract (TLR2eF)) and two recombinant proteins (rMAB_2545c and rMAB_0555 also known as the phospholipase C (rPLC)). RESULTS: TLR2eF and rPLC were the most efficient antigens to discriminate NTM-culture positive CF-patients from NTM-culture negative CF-patients. The best clinical values were obtained for the detection of M. abscessus-culture positive CF-patients; with sensitivities for the TLR2eF and rPLC of 81.2% (95% CI:65.7-92.3%) and 87.9% (95% CI:71.9-95.6%) respectively, and specificities of 88.9% (95% CI:85.3-94.8%) and 84.8% (95% CI:80.6-91.5%) respectively. When considering as positive all sera, giving a positive response in at least one of the two tests, and, as negative, all sera negative for both tests, we obtained a sensitivity of 93.9% and a specificity of 80.7% for the detection of M. abscessus-culture positive CF-patients. CONCLUSION: High antibody titers against TLR2eF and rPLC were obtained in M. abscessus-culture positive CF-patients, allowing us to consider these serological markers as potential tools in the detection of CF-patients infected with M. abscessus.
BACKGROUND: Culture conditions sometimes make it difficult to detect non-tuberculous mycobacteria (NTM), particularly Mycobacterium abscessus, an emerging cystic fibrosis (CF) pathogen. The diagnosis of NTM positive cases not detected by classical culture methods might benefit from the development of a serological assay. METHODS: As part of a diagnostic accuracy study, a total of 173 sera CF-patients, including 33 patients with M. abscessus positive cultures, and 31 non-CF healthy controls (HC) were evaluated. Four M. abscessus antigens were used separately, comprising two surface extracts (Interphase (INP) and a TLR2 positive extract (TLR2eF)) and two recombinant proteins (rMAB_2545c and rMAB_0555 also known as the phospholipase C (rPLC)). RESULTS: TLR2eF and rPLC were the most efficient antigens to discriminate NTM-culture positive CF-patients from NTM-culture negative CF-patients. The best clinical values were obtained for the detection of M. abscessus-culture positive CF-patients; with sensitivities for the TLR2eF and rPLC of 81.2% (95% CI:65.7-92.3%) and 87.9% (95% CI:71.9-95.6%) respectively, and specificities of 88.9% (95% CI:85.3-94.8%) and 84.8% (95% CI:80.6-91.5%) respectively. When considering as positive all sera, giving a positive response in at least one of the two tests, and, as negative, all sera negative for both tests, we obtained a sensitivity of 93.9% and a specificity of 80.7% for the detection of M. abscessus-culture positive CF-patients. CONCLUSION: High antibody titers against TLR2eF and rPLC were obtained in M. abscessus-culture positive CF-patients, allowing us to consider these serological markers as potential tools in the detection of CF-patients infected with M. abscessus.
Authors: Kenneth C Malcolm; Emily A Wheeler; Kara Calhoun; Patricia M Lenhart-Pendergrass; Noel Rysavy; Katie R Poch; Silvia M Caceres; Milene T Saavedra; Jerry A Nick Journal: Microbiol Spectr Date: 2022-07-06