Anti-heparin platelet factor 4 antibodies in systemic lupus erythematosus are associated with IgM antiphospholipid antibodies and the antiphospholipid syndrome.
OBJECTIVE
To investigate the prevalence and clinical correlates of anti-heparin platelet factor 4 antibodies (anti-HPF4) in systemic lupus erythematosus (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-beta2-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-beta2GP1, 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.
Alpert
D
D
Department of Rheumatology, Hospital for Special Surgery, New York, USA. alperd01@hotmail.com
Mandl
L A
LA
Erkan
D
D
Yin
W
W
Peerschke
E I
EI
Salmon
J E
JE
D000293:Adolescent; D000328:Adult; D000368:Aged; D017152:Antibodies, Antiphospholipid / Q000097:blood; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D006493:Heparin / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000276:immunology*; D008875:Middle Aged; D010978:Platelet Factor 4 / Q000276:immunology*; D012189:Retrospective Studies
D017152:Antibodies, Antiphospholipid; D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010978:Platelet Factor 4; D006493:Heparin