Anti–Neutrophil Extracellular Trap Antibodies in Antiphospholipid Antibody–Positive Patients: Results From the Antiphospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking Clinical Database and Repository

作者：Yu Zuo, Sherwin Navaz, Alex Tsodikov, Katarína Kmeťová, Lyndsay Kluge, Amala Ambati, Claire K. Hoy, Srilakshmi Yalavarthi, Danieli Andrade, Maria G. Tektonidou, Savino Sciascia, Vittorio Pengo, Guillermo Ruiz‐Irastorza, H. Michael Belmont, Maria Gerosa, Paul R. Fortin, Guilherme Ramires de Jesús, D. Ware Branch, Laura Andréoli, Esther Rodríguez-Almaraz, Michelle Petri, Ricard Cervera, Rohan Willis, David R. Karp, Quan‐Zhen Li, Hannah Cohen, María Laura Bertolaccini, Doruk Erkan, Jason S. Knight · 发表于：Arthritis & Rheumatology · 年份：2023 · DOI：10.1002/art.42489 · 被引用次数：43 · 研究领域：Systemic Lupus Erythematosus Research、Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Blood disorders and treatments

OBJECTIVE: This study aimed to elucidate the presence, antigen specificities, and potential clinical associations of anti-neutrophil extracellular trap (anti-NET) antibodies in a multinational cohort of antiphospholipid (aPL) antibody-positive patients who did not have lupus. METHODS: Anti-NET IgG/IgM levels were measured in serum samples from 389 aPL-positive patients; 308 patients met the classification criteria for antiphospholipid syndrome. Multivariate logistic regression with best variable model selection was used to determine clinical associations. For a subset of the patients (n = 214), we profiled autoantibodies using an autoantigen microarray platform. RESULTS: We found elevated levels of anti-NET IgG and/or IgM in 45% of the aPL-positive patients. High anti-NET antibody levels are associated with more circulating myeloperoxidase (MPO)-DNA complexes, which are a biomarker of NETs. When considering clinical manifestations, positive anti-NET IgG was associated with lesions affecting the white matter of the brain, even after adjusting for demographic variables and aPL profiles. Anti-NET IgM tracked with complement consumption after controlling for aPL profiles; furthermore, patient serum samples containing high levels of anti-NET IgM efficiently deposited complement C3d on NETs. As determined by autoantigen microarray, positive testing for anti-NET IgG was significantly associated with several autoantibodies, including those recognizing citrullinated histones, heparan ...