Session Type: Abstract Submissions (ACR)
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.
To determine PF-4var plasma levels and platelet PF-4var expression (RNA level) in patients with APS and evaluate the correlation with clinical and laboratory parameters of the disease.
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=30) and a disease control group (SLE, n=26) were included in the study.
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.
Platelet PF-4var and PF4 RNA levels were determined in RNA isolated from donor’s and patient’s platelet preparations using quantitative Real-Time PCR.
APS patients showed higher levels of plasma 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). In addition, RT-PCR revealed significantly higher PF-4var expression in platelets derived from patients comparing to healthy donors (2–ΔΔCT: 1.540; [1.020-1.943] versus 0.89 [0.705-1.203], p<0.001). 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).
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.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/plasma-levels-of-pf-4varcxcl4l1-a-non-allelic-variant-of-platelet-factor-4-pf-4cxcl4-are-elevated-in-patients-with-antiphospholipid-syndrome-aps/