Session Information
Title: Antiphospholipid Syndrome: Clinical Manifestations and New Biomarkers in Antiphospholipid Syndrome
Session Type: Abstract Submissions (ACR)
Background/Purpose:
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.
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=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.
Results:
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).
Conclusion:
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:
M. Sikara,
None;
M. Patsouras,
None;
E. Eliopoulos,
None;
P. Vlachoyiannopoulos,
None.
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/