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Anti-neutrophil extracellular trap antibodies in autoimmune rheumatic diseases: a suitable biomarker of thrombosis in systemic lupus erythematosus

1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11

 

  1. Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Italy.
  2. Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Italy. luca.rapino@uniroma1.it
  3. Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Italy.
  4. Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Italy.
  5. Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Italy.
  6. Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Italy.
  7. Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università di Roma; and Dipartimento di Medicina Interna e Specialità Mediche, AOU Policlinico Umberto I, Rome, Italy.
  8. Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Italy.
  9. Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Italy.
  10. Department of Internal Medicine, University Hospital Shefqet Ndroqi, Tirana, Albania.
  11. Reumatologia, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Italy.

CER19344
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PMID: 42154658 [PubMed]

Received: 23/09/2025
Accepted : 14/01/2026
In Press: 18/05/2026

Abstract

OBJECTIVES:
This case-control study aimed to elucidate the prevalence and role as biomarker of anti-neutrophil extracellular trap (anti-NET) antibodies in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and systemic sclerosis (SSc).
METHODS:
Serum samples from SLE, RA, SSc and healthy donors (HD) were evaluated for anti-NETs IgG, using an ELISA home-made coated with phorbol myristate acetate (PMA)-induced NET. Based on a positivity threshold set at the 99th percentile for HD sera, we calculated the positive samples.
RESULTS:
We enrolled 349 patients with autoimmune rheumatic diseases (ARD), finding a prevalence of anti-NETs of about 40%. Of the 136 SLE patients 50 (36.8%) were anti-NETs positive, revealing an association between anti-NETs and antiphospholipid syndrome (APS) (OR 3.37 [95% CI 1.22–9.36], p=0.02) and with arterial thrombosis regardless of coexisting APS (OR 5.52 [95% CI 1.07–28.52], p=0.032). In RA patients 52 out 131 (39.7%) tested positive for anti-NETs and we found a significant association between testing positive for anti-NETs and the presence of ACPA (p=0.049). Of the 82 SSc patients enrolled 33 (40%) were anti-NETs positive, and we found a direct correlation with CCL-18 (r 0.289 [CI 95% 0.04–0.50], p=0.02), a biomarker of worst prognosis and mortality in ILD-SSc patients.
CONCLUSIONS:
In SLE patients, anti-NETs could have a role as a biomarker of thrombosis, a major cause of mortality in SLE.

DOI: https://doi.org/10.55563/clinexprheumatol/crnzs0

Rheumatology Article