OBJECTIVE: Antibodies that recognize complexes formed by platelet factor 4 (PF4) and heparin are involved in the pathogenesis of heparin-induced thrombocytopenia (HIT). This study was undertaken to investigate the prevalence and clinical correlations of anti-PF4 autoantibodies in patients with SLE. METHODS: We studied 118 patients with SLE, 78 with primary immune thrombocytopenia (ITP), 27 with primary APS, 2 with HIT (as positive controls) and 47 healthy controls. Heparin-dependent and -independent anti-PF4 antibodies were measured with an ELISA. Antibody binding was confirmed to be heparin-dependent when inhibited by the presence of a high concentration of heparin. Pathogenic anti-PF4 antibody was assessed by serotonin-release assay. RESULTS: Heparin-dependent anti-PF4 antibodies were detected in 11 SLE (9%) and 2 primary ITP (3%) patients, but at much lower levels than in HIT patients. In serotonin-release assays, only the HIT sera induced platelet activation in vitro. Heparin-independent anti-PF4 antibodies were detected in 17 SLE patients (14%). There was no correlation between the levels of heparin-dependent and -independent anti-PF4 antibodies. Cross-reactivity between these two antibodies was not detectable by ELISA competitive assay. Heparin-dependent anti-PF4 antibodies were associated with thrombocytopenia and IgM aCLs (P = 0.007 for both comparisons), while heparin-independent anti-PF4 antibody levels were correlated with SLE disease activity index (P = 0.0005). None of the SLE patients with anti-PF4 antibodies had previous heparin exposure. CONCLUSION: PF4 is an autoimmune target in SLE patients. Heparin-dependent and -independent anti-PF4 autoantibodies may be involved in different aspects of pathophysiology of SLE.
OBJECTIVE: Antibodies that recognize complexes formed by platelet factor 4 (PF4) and heparin are involved in the pathogenesis of heparin-induced thrombocytopenia (HIT). This study was undertaken to investigate the prevalence and clinical correlations of anti-PF4 autoantibodies in patients with SLE. METHODS: We studied 118 patients with SLE, 78 with primary immune thrombocytopenia (ITP), 27 with primary APS, 2 with HIT (as positive controls) and 47 healthy controls. Heparin-dependent and -independent anti-PF4 antibodies were measured with an ELISA. Antibody binding was confirmed to be heparin-dependent when inhibited by the presence of a high concentration of heparin. Pathogenic anti-PF4 antibody was assessed by serotonin-release assay. RESULTS:Heparin-dependent anti-PF4 antibodies were detected in 11 SLE (9%) and 2 primary ITP (3%) patients, but at much lower levels than in HITpatients. In serotonin-release assays, only the HIT sera induced platelet activation in vitro. Heparin-independent anti-PF4 antibodies were detected in 17 SLEpatients (14%). There was no correlation between the levels of heparin-dependent and -independent anti-PF4 antibodies. Cross-reactivity between these two antibodies was not detectable by ELISA competitive assay. Heparin-dependent anti-PF4 antibodies were associated with thrombocytopenia and IgM aCLs (P = 0.007 for both comparisons), while heparin-independent anti-PF4 antibody levels were correlated with SLE disease activity index (P = 0.0005). None of the SLEpatients with anti-PF4 antibodies had previous heparin exposure. CONCLUSION:PF4 is an autoimmune target in SLEpatients. Heparin-dependent and -independent anti-PF4 autoantibodies may be involved in different aspects of pathophysiology of SLE.