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

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Citações na Scopus
15
Tipo de produção
article
Data de publicação
2023
DOI
Scopus
Web of Science
PubMed
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Título do Volume
Editora
WILEY
Autores
ZUO, Yu
NAVAZ, Sherwin
TSODIKOV, Alex
KMETOVA, Katarina
KLUGE, Lyndsay
AMBATI, Amala
HOY, Claire K.
YALAVARTHI, Srilakshmi
TEKTONIDOU, Maria G.
Citação
ARTHRITIS & RHEUMATOLOGY, v.75, n.8, p.1407-1414, 2023
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
ObjectiveThis 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. MethodsAnti-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. ResultsWe 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. ConclusionThese 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.
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URI
https://observatorio.fm.usp.br/handle/OPI/59207
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Coleções
Artigos e Materiais de Revistas Científicas - HC/ICHC