Primary antiphospholipid syndrome: A low-grade auto-inflammatory disease?

Objective. To test the inflammation and immune activation hypothesis in primary thrombotic APS (PAPS) and to identify clinical and laboratory factors related to inflammation and immune activation. Methods. PAPS (n = 41) patients were compared with patients with inherited thrombophilia (IT, n = 44) and controls (CTR, n = 39). IgG aCL, IgG anti-β2-glycoprotein I (β₂GPI), high-sensitivity CRP (hs-CRP), serum amyloid A (SAA), CRP bound to oxidized low-density lipoprotein-β₂GPI complex (CRP-oxLDL-β₂ GPI) (as inflammatory markers) neopterin (NPT), soluble CD14 (sCD14) (as immune activation markers) were measured by ELISA. Results. After correction for confounders, PAPS showed higher plasma levels of hs-CRP (P = 0.0004), SAA (P = 0.01), CRP-oxLDL-β₂GPI (P = 0.0004), NPT (P = 0.0001) and sCD14 (P = 0.007) than IT and CTR. Two regression models were applied to the PAPS group: in the first, IgG aCL and IgG β₂GPI were included amongst the independent variables and in the second they were excluded. In the first model, SAA (as the dependent variable) independently related to thrombosis number (P = 0.003); NPT (as the dependent variable) independently related to thrombosis type (arterial, P = 0.03) and number (P = 0.04); sCD14 (as the dependent variable) independently related to IgG β₂ GPI (P = 0.0001), age (0.001) and arterial thrombosis (P = 0.01); CRP-oxLDL-β₂ GPI (as the dependent variable) independently related to IgG β₂GPI (P = 0.0001). In the second model, sCD14 and NPT independently related to each other (P = 0.002) (this was noted also in the IT group, P = 0.0001) and CRP-oxLDL-β₂GPI independently predicted SAA (P = 0.002). Conclusion. Low-grade inflammation and immune activation occur in thrombotic PAPS and relate to clinical features and aPL levels.