Background/Purpose : Primary antiphospholipid syndrome (PAPS) is characterized by thrombotic and/or obstetrical morbidity in the presence of persistent antiphospholipid antibodies (APLA) and in the absence of other autoimmune disease. APLA are necessary, but not sufficient for the clinical manifestations of APS. Triggering receptor expressed on myeloid cells-1 (TREM-1) is an innate-immune cell-surface receptor involved in amplification of TLR-4-mediated inflammatory response. Soluble TREM-1 (sTREM-1) reflects membrane TREM-1 upregulation and exerts an anti-inflammatory effect. Aim: To determine plasma level of sTREM-1 in patients with PAPS.

Methods: A cross-sectional, case-control study. Plasma level of sTREM-1 was analyzed by ELISA in a cohort of consecutively recruited patients diagnosed with PAPS (defined by Sapporo criteria), asymptomatic patients with persistently positive APLA, and healthy controls (HC). Patients diagnosed with other inflammatory disease, and/or with concurrent infection, and/or malignancy as well as during pregnancy or puerperium were excluded.

Results: The study groups comprised of 36 patients with PAPS (age 50.25±16.4 yrs.), 10 asymptomatic APLA-positive patients (53.5±18.4 yrs.) and 21 HC (30.19±6.3 yrs.). Of the PAPS group, 30 patients (83.3%) had thrombotic and/or obstetrical features prior to the study encounter (past PAPS), while 6 patients (16.7%) were evaluated at the time of PAPS-related thrombotic event (current thrombotic PAPS).  The mean plasma sTREM-1 level was significantly greater in the PAPS group compared to HC (98.1±95.0 pg/ml, vs. 45.5±10.46 pg/ml, p=0.0013), between current thrombotic PAPS and HC (p=0.0002) and asymptomatic APLA (64.3±28.7 pg/ml, p=0.03), as well as between past PAPS and HC (p=0.02). Plasma sTREM-1 was positively correlated with older age (r=0.59, p<0.0001), higher ferritin level (r=0.44, p=0.005), higher ESR (r=0.43, p=0.003) as well as with elevated serum creatinine (r=0.64, p<0.0001) and lower eGFR (r=-0.63, p<0.0001). Plasma level of sTREM-1 was not different in the asymptomatic APLA group compared to HC. Plasma sTREM-1 level was significantly higher in the PAPS patients who ever had MI (p<0.001), stroke (p=0.02), venous thrombophlebitis (p=0.02), pulmonary embolism (p=0.001), and arterial thrombosis (p<0.0001). Plasma sTREM-1 level was neither associated with anti-cardiolipin, anti-β₂ glycoprotein I (IgG/IgM/IgA) Abs’ titers and/or lupus anticoagulant positivity, nor with single-, double- or triple- APLA positivity. A multivariate regression model was used to predict the sTREM-1 level by thrombotic PAPS ever, age, diabetes mellitus, hypertension and dyslipidemia found that sTREM-1 level is independently associated with thrombotic PAPS (p = 0.001).

Conclusion: Our data show for the first time that plasma sTREM-1 level is significantly elevated in patients with PAPS as well as during a thrombotic PAPS event. Soluble TREM-1 might be used as a biomarker for thrombosis in patients with PAPS.