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Relevance of inflammatory and complement activation biomarkers profiling in antiphospholipid syndrome patients outside acute thrombosis

1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12

 

  1. Département de Médecine Interne et d’Immunologie Clinique, Centre National de Référence Maladies Systémiques et Auto-immunes Rares Nord et Nord-Ouest de France (CeRAINO), European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNECT), Université de Lille, CHU Lille; and INSERM, UMR 1167, RID-AGE, Lille, France. cecile.yelnik@orange.fr
  2. Département de Médecine Interne et d’Immunologie Clinique, Centre National de Référence Maladies Systémiques et Auto-immunes Rares Nord et Nord-Ouest de France (CeRAINO), European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNECT), Université de Lille, CHU Lille; and INSERM, UMR 1167, RID-AGE, Lille, France.
  3. Université de Lille, CHU Lille, ULR 2694 - METRICS: Évaluation des Technologies de Santé et des Pratiques Médicales, Lille; and Département de Biostatistiques, CHU Lille, France.
  4. Université de Lille, CHU Lille, ULR 2694 - METRICS: Évaluation des Technologies de Santé et des Pratiques Médicales, Lille; and Département de Biostatistiques, CHU Lille, France.
  5. INSERM, UMR 1167, RID-AGE, Lille, France.
  6. Département de Médecine Interne et d’Immunologie Clinique, Centre National de Référence Maladies Systémiques et Auto-immunes Rares Nord et Nord-Ouest de France (CeRAINO), European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNECT), Université de Lille, CHU Lille, France.
  7. Département de Médecine Interne et d’Immunologie Clinique, Centre National de Référence Maladies Systémiques et Auto-immunes Rares Nord et Nord-Ouest de France (CeRAINO), European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNECT), Université de Lille, CHU Lille, France.
  8. Immunologie, Centre de Biologie Pathologie, Université de Lille, CHU Lille, France.
  9. Immunologie, Centre de Biologie Pathologie, Université de Lille, CHU Lille, France.
  10. INSERM, UMR 1167, RID-AGE, Lille, France.
  11. INSERM, UMR 1167, RID-AGE, Lille, France.
  12. INSERM, UMR 1167, RID-AGE, Lille, and Département de Néphrologie, Université de Lille, CHU Lille, France.

CER16261
2023 Vol.41, N°9
PI 1875, PF 1881
Full Papers

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PMID: 37279145 [PubMed]

Received: 06/10/2022
Accepted : 26/01/2023
In Press: 06/06/2023
Published: 17/08/2023

Abstract

OBJECTIVES:
To evaluate whether inflammatory and complement biomarkers are associated with specific characteristics of antiphospholipid syndrome (APS).
METHODS:
Serum levels of interleukin (IL)-1β (IL-1β), IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-α, interferon-α (IFN)-α, IFN-γ, vascular endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1), E-selectin, and vascular cell adhesion molecule (VCAM)-1, and plasma levels of soluble C5b-9 (sC5b-9), C3a, C4a, Bb fragment were measured in unselected APS patients. Twenty-five healthy blood donors were included as controls.
RESULTS:
Between January 2020 and April 2021, 98 APS patients were included outside acute thrombosis (median time from the last APS manifestation: 60 (23;132) months). Levels of IL6, VCAM-1, sC5b-9, C3a, C4a, and Bb were significantly increased in APS patients compared to controls. A cluster analysis allowed to divide patients into two clusters: “inflammatory” (higher levels of IL-6 and VCAM-1) and “complement”. In APS, elevated IL-6 was associated with hypertension, diabetes, BMI, and hypertriglyceridaemia. 85% of our APS patients had elevated levels of at least one complement biomarker. Elevated Bb (34%) was associated with aPL positivities, especially with triple aPL positivity (50% vs. 18%, p<0.001). 7/8 patients with history of catastrophic APS had elevated levels of complement biomarkers.
CONCLUSIONS:
Our findings suggested that APS patients outside acute thrombosis might be divided into two clusters: “inflammatory” and “complement”. Elevated IL-6 was associated with cardiovascular risk factors and metabolic parameters, whereas Bb fragments, a marker of alternative pathway complement activation, was strongly associated with aPL profile at highest risk of severe disease.

DOI: https://doi.org/10.55563/clinexprheumatol/ric86c

Rheumatology Article