Clinical Efficacy of Serum Anti-glycopeptidolipid-core IgA Antibody Test for Screening Nontuberculous Mycobacterial Pulmonary Disease in Bronchiectasis: A European Multicenter Cohort Study

Hayoung Choi; Chloe Hughes; Zsofia Eke; Morven Shuttleworth; Michal Shteinberg; Eva Polverino; Pieter C Goeminne; Tobias Welte; Francesco Blasi; Amelia Shoemark; Merete B Long; Stefano Aliberti; Charles S Haworth; Felix C Ringshausen; Michael R Loebinger; Natalie Lorent; James D Chalmers

doi:10.1016/j.chest.2024.10.029

Clinical Efficacy of Serum Anti-glycopeptidolipid-core IgA Antibody Test for Screening Nontuberculous Mycobacterial Pulmonary Disease in Bronchiectasis: A European Multicenter Cohort Study

Chest. 2024 Oct 25:S0012-3692(24)05418-7. doi: 10.1016/j.chest.2024.10.029. Online ahead of print.

Authors

Hayoung Choi¹, Chloe Hughes², Zsofia Eke², Morven Shuttleworth², Michal Shteinberg³, Eva Polverino⁴, Pieter C Goeminne⁵, Tobias Welte⁶, Francesco Blasi⁷, Amelia Shoemark², Merete B Long², Stefano Aliberti⁸, Charles S Haworth⁹, Felix C Ringshausen¹⁰, Michael R Loebinger¹¹, Natalie Lorent¹², James D Chalmers¹³

Affiliations

¹ Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea.
² Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
³ Pulmonology Institute and CF Center, Carmel Medical Center and the Technion - Israel Institute of Technology, the B. Rappaport Faculty of Medicine, Haifa, Israel.
⁴ Hospital Clinic of Barcelona, Spain University of Barcelona, CIBERES, IDIBAPS, Barcelona, Spain.
⁵ Department of Respiratory Disease, AZ Nikolaas, Belgium.
⁶ Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany.
⁷ Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Italy; Respiratory Unit and Cystic Fibrosis Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico Milano, Italy.
⁸ Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072, Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Respiratory Unit, Via Manzoni 56, 20089, Rozzano, Milan, Italy.
⁹ Cambridge Centre for Lung Infection, Royal Papworth Hospital and University of Cambridge, Cambridge, United Kingdom.
¹⁰ Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany; Biomedical Research in End-Stage and Obstructive Lung Disease Hannover, German Center for Lung Research, Hannover, Germany; European Reference Network on Rare and Complex Respiratory Diseases, Frankfurt, Germany.
¹¹ Host Defence Unit, Department of Respiratory Medicine, Royal Brompton Hospital and Harefield NHS Foundation Trust, London, United Kingdom and NHLI, Imperial College London.
¹² Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium and Department of Chronic Diseases, Metabolism and Aging, BREATHE laboratory, KU Leuven, Leuven, Belgium.
¹³ Division of Molecular and Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom. Electronic address: [email protected].

PMID: 39490969
DOI: 10.1016/j.chest.2024.10.029

Abstract

Background: Serum anti-glycopeptidolipid (GPL) core immunoglobuin A (IgA) antibody test has been proposed as a diagnostic tool for Mycobacterium avium complex pulmonary diseases. Cross-reactivity with other non-tuberculous mycobacteria (NTM), including M. abscessus, indicates that it may have a role as a broader screening test for NTM pulmonary disease (NTM-PD). NTM-PD is believed to be underdiagnosed in patients with bronchiectasis.

Research question: Can the serum anti-GPL core IgA antibody test be used to screen for NTM-PD in bronchiectasis?

Study design and methods: Patients from the prospective European Bronchiectasis Registry (EMBARC-BRIDGE; NCT03791086) were enrolled. Patients from the United Kingdom, Italy, Spain, Belgium, the Netherlands, and Germany were included. A control cohort of patients without any underlying lung disease was also recruited. The levels of serum IgA antibodies against the GPL core were measured using an enzyme immunoassay kit, and receiver operating characteristics curve analysis was conducted to evaluate the accuracy of the antibody level in screening for NTM-PD.

Results: 282 patients were enrolled (151 [53.6%] female, median age 68 years). Median (quartile 1-3) anti-GPL-core IgA antibody levels were 0.2 (0.1-0.3) U/mL in patients without NTM isolation and NTM-PD (n=238), 0.3 (0.2-0.4) U/mL in NTM isolation that were incompatible with the diagnosis of NTM-PD (n=18) and 1.5 (0.4-6.2) U/mL in NTM-PD (n=26) (P=0.0001). Antibody levels showed excellent accuracy in identifying patients with NTM-PD (area under the curve 0.886, 95% CI 0.800-0.973) in bronchiectasis cohort and also showed excellent discrimination of patients with NTM-PD from those with NTM isolation who did not meet the diagnostic criteria for NTM-PD (0.816, 95% CI 0.687-0.945).

Interpretation: The anti-GPL-core IgA antibody demonstrated excellent efficacy in screening for NTM-PD in a large bronchiectasis cohort.

Keywords: anti-glycopeptidolipid-core IgA test; bronchiectasis; nontuberculous mycobacteria; serodiagnosis.