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FRI0273 Plasma levels of pf-4var/cxcl4l1, a nonallelic variant of platelet factor-4 (PF-4/CXCL4), are elevated in patients with antiphospholipid syndrome (APS).
  1. M. P. Sikara1,
  2. P. G. Vlachoyiannopoulos1
  1. 1Pathophysiology, School of Medicine, National University of Athens, Greece, Athens, Greece

Abstract

Background Platelet derived chemokines, such as PF-4 and a recently isolated protein product of its nonallelic variant gene PF-4var, are implicated in several aspects of vascular thrombosis and inflammation. The above chemokines present only 4.3% aminoacid divergence in the mature proteins; however they exhibit distinct platelet secretion mode and function. The precise role of PF-4var regarding the haemostatic balance is not yet studied.

Previous study from our group demonstrates a novel interaction between β2-glycoprotein I (β2GPI), the major autoantigen in APS, and PF-4 or PF-4var. This complex formation leads in the stabilization of β2GPI dimeric structure which facilitates the antibody recognition and platelet activation, as indicated by p38MAPK phosphorylation and thromboxane production.

Objectives To determine PF-4var plasma levels in patients with APS and evaluate the correlation with clinical and laboratory parameters of the disease.

Methods From 70 patients, who fulfill the revised diagnostic criteria for APS, blood samples were taken and separate samples of serum, plasma and platelets were isolated. Complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), aPTT, anti-cardiolipin (anti-CL) and anti-β2GPI antibodies were measured. A healthy control (n=20) and a disease control group (SLE, n=10) were included in the study (study in progress to increase the number of both groups).

Plasma levels of PF-4var were determined using a commercially available ELISA, which absolutely discriminates PF-4var from PF-4 protein. Statistical analyses were evaluated by Mann-Whitney t-test and Kruskal-Wallis test.

Results APS patients showed higher levels of PF-4var compared to healthy individuals (median 137 pg/ml; intarquartile range 66.4-200.5 pg/ml versus 79.03 [40.3-99.2] pg/ml, p=0.0052). PF-4var levels were significantly elevated in patients suffering from primary APS (PAPS) than those with APS secondary to SLE (SAPS), (197.7 [113.3-304.8] pg/ml versus 126.6 [49.94-170] pg/ml, p=0.0086). Regarding the clinical presentation of the disease, patients who experienced thrombotic events versus pregnancy morbidity or arterial versus venous thrombotic events do not show statistically significant difference in PF-4var levels. A positive correlation was also revealed between the presence of thrombocytopenia and the elongation of aPTT with the higher PF-4var levels (p= 0.0048 and p=0.0195, respectively).

Conclusions Preliminary results suggest that higher PF-4var levels are present in plasma of APS patients and especially in those with PAPS and these are associated with laboratory characteristics indicative for higher risk of thrombotic complications.

Disclosure of Interest: None Declared

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