Skip to main content
Journal cover image

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.

Publication ,  Journal Article
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 ...
Published in: Arthritis Rheumatol
August 2023

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Arthritis Rheumatol

DOI

EISSN

2326-5205

Publication Date

August 2023

Volume

75

Issue

8

Start / End Page

1407 / 1414

Location

United States

Related Subject Headings

  • Immunoglobulin M
  • Immunoglobulin G
  • Humans
  • Extracellular Traps
  • Autoantibodies
  • Antiphospholipid Syndrome
  • Antibodies, Antiphospholipid
  • 3204 Immunology
  • 3202 Clinical sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zuo, Y., Navaz, S., Tsodikov, A., Kmetova, K., Kluge, L., Ambati, A., … Antiphospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking, . (2023). 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. Arthritis Rheumatol, 75(8), 1407–1414. https://doi.org/10.1002/art.42489
Zuo, Yu, Sherwin Navaz, Alex Tsodikov, Katarina Kmetova, Lyndsay Kluge, Amala Ambati, Claire K. Hoy, et al. “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.Arthritis Rheumatol 75, no. 8 (August 2023): 1407–14. https://doi.org/10.1002/art.42489.
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 Q-Z, Cohen H, Bertolaccini ML, Erkan D, Knight JS, Antiphospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking. 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. Arthritis Rheumatol. 2023 Aug;75(8):1407–1414.
Journal cover image

Published In

Arthritis Rheumatol

DOI

EISSN

2326-5205

Publication Date

August 2023

Volume

75

Issue

8

Start / End Page

1407 / 1414

Location

United States

Related Subject Headings

  • Immunoglobulin M
  • Immunoglobulin G
  • Humans
  • Extracellular Traps
  • Autoantibodies
  • Antiphospholipid Syndrome
  • Antibodies, Antiphospholipid
  • 3204 Immunology
  • 3202 Clinical sciences