Objective: To investigate the prevalence and clinical correlates of anti-heparin platelet factor 4 antibodies (anti-HPF4) in SLE patients with and without antiphospholipid antibodies (aPL).
Methods: Sera and clinical data were obtained from the Hospital for Special Surgery Autoimmune Disease Registry for 78 aPL-positive and 91 aPL-negative SLE patients without heparin-induced thrombocytopenia (HIT). Controls were 90 blood donors of comparable age and sex. Sera were assayed for anti-HPF4, IgG/IgM antiphospholipid antibodies (APhL), and IgG/IgM-β2-glycoprotein 1 antibodies (anti-β2GP1). Serotonin release assays (SRAs) were performed for subjects with positive anti-HPF4.
Results: Positive anti-HPF4 was seen in 9% of aPL-positive SLE patients, 4% of aPL-negative SLE patients and 1% of controls (p-value = 0.026, aPL-positive SLE versus controls). Two of 12 subjects with positive anti-HPF4 had reactive SRAs. In SLE patients, anti-HPF4 significantly correlated with IgM APhL, IgM anti-β2GP1, and inversely with complement C4. In immunoabsorption experiments, there was partial cross-reactivity of IgM anti-HPF4 with IgM APhL, but not with IgM anti-β2GP1. SLE patients with positive anti-HPF4 had increased odds of the antiphospholipid syndrome (APS; OR = 4.5, p-value = 0.019), and APS with arterial thrombosis (OR = 6.1, p-value = 0.007). In multivariate linear regression analyses, APS and IgM APhL were independently associated with anti-HPF4.
Conclusions: Anti-HPF4 is detectable in SLE patients with and without aPL in the absence of HIT, and is most prevalent in aPL-positive SLE patients. In this SLE cohort, anti-HPF4 correlates with IgM APhL, IgM anti-β2GP1 and inversely with C4, and is associated with manifestations of APS.
- antiphospholipid antibodies
- heparin-induced thrombocytopenia
- platelet factor 4
- systemic lupus erythematosus
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