Background/Purpose: Platelet factor 4 (PF4), also called CXLC4 is a chemokine that is found in higher levels in systemic sclerosis (SSc) patients and is in particular associated with lung involvement and early diffuse disease, conditions which are correlated with certain SSc auto antibody types. PF4 is also the antigenic target, when combined with heparin complexes, involved in heparin induced thrombocytopenia (HIT). Anti-PF4 antibodies, both heparin dependant and independent, are more prevalent in systemic lupus erythematous (SLE) patients and murine models suggest increased anti heparin antibodies in SSc(1). Our aim was to examine whether certain SSc patients then also had an associated increase in heparin dependant anti PF4-heparin antibodies.

Methods: 102 patients’ sera from our SSc patient bank, recruited from consenting adult patients with a diagnosis of SSc established between 1988 and 1995, were randomly selected, each with a particular SSc related antibody (anti centromere (ACA), anti topoisomerase I antibody (ATA), RNA polymerase III (RNAP), anti Th/To). Each patient serum was tested for the presence of anti PF4-heparin antibodies using ELISA technique. A second group of SLE patients were also tested and acted as controls. Patient files were reviewed for comorbidities, type of SSc, and the presence of interstitial lung disease.

Results: A total of 102 SSc patients, split as follows: 20 with ATA antibodies, 20 with anti Th/To, 31 with ACA and 31 with RNAP. There was no significant differences in the presence of anti PF4-heparin between each SSc antibody subgroup, at 5%, 5%, 6.4% and 0% respectively. 26 patients (25.5%) had ILD, in particular 65% of ATA patients. 3.8% compared to 3.9% (p=1) of patients with and without ILD had anti PF4-heparin antibodies respectively. No patient with diffuse cutaneous SSc had anti PF4-heparin antibodies compared to 4.9% of patients with limited cutaneous disease (p=0.58). Of the 21 lupus patients, 14% of patients had anti PF4-heparin compared to 3.9% of 102 of SSc patients (p=0.095). None of these patients had any documented HIT.

Conclusion: Despite previously demonstrated increased PF4 or CXCL4 levels, there does not seem to be an associated increase in anti PF4-heparin antibodies in SSc patients, either with or without ILD. There is no indication that these patients will accrue false positives on HIT screening, which are based on anti PF4-heparin detection, and there are no direct antigenic arguments for an increased risk of HIT itself. This may provide insight into the antigenicity of CXCL4, although it may be interesting to examine the presence of heparin independent PF4 antibodies.

1. Matic M, Shibata S, Fillit HM. Monoclonal antibody to heparan sulfate from autoimmune tight skin (TSK) mice binds to the endothelial cell surface. Immunol Invest 1997;26:371-81.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-cxcl4pf4-presence-in-systemic-sclerosis-and-absence-of-heparin-directed-autoantibodies/