دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: 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
المؤلفون: Zuo, Y, Navaz, S, Tsodikov, A, Kmetova, K, Kluge, L, Ambati, A, Hoy, CK, Yalavarthi, S, de Andrade, D, Tektonidou, MG, Sciascia, S, Pengo, V, Ruiz-Irastorza, G, Belmont, HM, Gerosa, M, Fortin, PR, de Jesus, GR, Branch, DW, Andreoli, L, Rodriguez-Almaraz, E, Petri, M, Cervera, R, Willis, R, Karp, DR, Li, QZ, Cohen, H, Bertolaccini, ML, Erkan, D, Knight, JS, Pons-Estel, G, Giannakopoulos, B, Krilis, S, de Jesus, G, Levy, R, Signorelli, F, Andrade, D, Balbi, G, Clarke, AE, Skeith, L, Ji, L, Zhang, Z, Yang, C, Shi, H, Zuily, S, Wahl, D, Nalli, C, Tincani, A, Chighizola, CB, Meroni, P, Cheng, C, Pazzola, G, Foddai, S, Radin, M, Davis, S, Amengual, O, Atsumi, T, Uthman, I, Limper, M, de Groot, P, Ugarte, A, Rodriguez-Pinto, I, Ríos-Garcés, R, Barilaro, G, Pardos-Gea, J, Almaraz, ER, Cuadrado, MJ, Zamorano, MAA, Lopez-Pedrera, C, Artim-Esen, B, Inanc, M, Efthymiou, M, Khamashta, M, Mackie, I, Sanna, G, Knight, J, Leaf, RK, Roubey, R, Ortel, T, Gonzalez, E, Kello, N, Belmont, M, Levine, S, Rand, J, Barbhaiya, M, Salmon, J, Lockshin, M
المصدر: Arthritis & Rheumatology (2023) (In press).
بيانات النشر: Wiley
سنة النشر: 2023
المجموعة: University College London: UCL Discovery
الوصف: 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 sulfate proteoglycan, laminin, MPO–DNA complexes, and nucleosomes. Anti-NET IgM positivity was associated with autoantibodies targeting single-stranded DNA, double-stranded DNA, and proliferating cell nuclear antigen. CONCLUSION: These data reveal high levels of anti-NET antibodies in 45% of aPL-positive patients, where they potentially activate the complement cascade. While anti-NET IgM may especially recognize DNA in NETs, anti-NET IgG species appear to be more likely to target NET-associated protein antigens.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
العلاقة: https://discovery.ucl.ac.uk/id/eprint/10171637/1/Anti%20Neutrophil%20Extracellular%20Trap%20Antibodies%20in%20Antiphospholipid%20Antibody%20Positive.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10171637Test/
الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10171637/1/Anti%20Neutrophil%20Extracellular%20Trap%20Antibodies%20in%20Antiphospholipid%20Antibody%20Positive.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10171637Test/
حقوق: open
رقم الانضمام: edsbas.2ED965A9
قاعدة البيانات: BASE