Elevated Levels of Cytokines and Chemokines in Patients with Antiphospholipid (aPL) Antibodies.

Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS) are two closely related diseases. APL antibodies are present in 30-40% of SLE patients. Studies have indicated that certain cytokines, chemokines, tissue factor (TF), vascular endothelial growth factor (VEGF), soluble (s) E-selectin (sE-sel), tumor necrosis (TNF)-a, may be associated with APS and/or SLE. However, whether those biomarkers are elevated in plasma of APS patients with or without SLE is uncertain. Here we examined whether the levels of cytokines/chemokines in aPL antibody-positive patients positive are different from controls.

Twenty-two sera/plasma of patients with significantly and persistently elevated levels aPL antibodies (IgG and/or IgM aCL, and/or IgG and/or IgM anti-β2glycoprotein I (β2GPI) and/or positive lupus anticoagulant (LAC), demographic and clinical data were obtained from an on-going pilot clinical study (clinical trials.gov#NCT00674297). Patients that were on more than 10 mg prednisone/day, or on other immunosuppressive therapy, or on hydroxychloroquine or on statins were excluded. Thirty-two healthy donors with no evidence of autoimmune, infectious or inflammatory diseases were used as controls. .Levels of IL1b, IL6, IL8, TNF-a, VEGF, IP-10, sCD40L were measured in serum using a Millipore Millliplex” Multiplex Assay; titers of sE-sel, and sTF were detected by ELISA. The Kruskal-Wallis test was used to compare levels of biomarkers in aPL positive subjects vs. controls and Spearman tests to correlate levels of the biomarkers in the different subgroups of patients.

Significant number of aPL-positive samples had elevated levels of IL1b, IL6, TNF-a, VEGF, IP-10, sCD40L, sTF, sCD40L and sE-sel and their titers were significantly different when compared to controls. APS /SLE patients (n=8) showed significantly higher levels of TNF-a compared to APS without SLE (n=6), to “asymptomatic” aPL positive (n=4), to “asymptomatic” aPL positive with SLE (n=2) or with “catastrophic” APS (n=2) patients (p=0.00630).

This study underscores the importance of identifying biomarkers of disease that may help to better understand pathogenic mechanisms, predict disease activity and possibly to better address treatment of patients with aPL antibodies.

No relevant conflicts of interest to declare.