Heparin-dependent and -independent anti-platelet factor 4 autoantibodies in patients with systemic lupus erythematosus.
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.


CONCLUSIONS
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.
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan.
Takashi
T
Satoh
Yoko
Y
Tanaka
Yuka
Y
Okazaki
Junichi
J
Kaburaki
Yasuo
Y
Ikeda
Masataka
M
Kuwana
D000328:Adult; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000175:diagnosis / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000175:diagnosis / Q000276:immunology*; D008297:Male; D010978:Platelet Factor 4 / Q000276:immunology*; D012720:Severity of Illness Index; D013921:Thrombocytopenia / Q000139:chemically induced / Q000175:diagnosis / Q000276:immunology*
D001323:Autoantibodies; D010978:Platelet Factor 4; D006493:Heparin