Journal
ANNALS OF THE RHEUMATIC DISEASES
Volume 67, Issue 3, Pages 395-401Publisher
B M J PUBLISHING GROUP
DOI: 10.1136/ard.2007.074476
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Funding
- NHLBI NIH HHS [HL067211] Funding Source: Medline
- NIAMS NIH HHS [K23 AR050607-01] Funding Source: Medline
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Objective: To investigate the prevalence and clinical correlates of anti-heparin platelet factor 4 antibodies (anti-HPF4) in systemic lupus erythaematosus (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 anti-beta 2-glycoprotein 1 antibodies (anti-beta 2GP1). 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=0.026, aPL-positive SLE vs controls). Two of 12 subjects with positive anti-HPF4 had reactive SRAs. In SLE patients, anti-HPF4 significantly correlated with IgM APhL, IgM anti-beta 2GP1, 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-beta 2GP1. SLE patients with positive anti-HPF4 had increased odds of the antiphospholipid syndrome (APS; odds ratio (OR) 4.5, p=0.019), and APS with arterial thrombosis (OR 6.1, p=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-beta 2GP1 and inversely with C4, and is associated with manifestations of APS.
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