Elevated plasma level of soluble triggering receptor expressed on myeloid cells-1 is associated with inflammation activity and is a potential biomarker of thrombosis in primary antiphospholipid syndrome

Yonatan Edel, Vitaly Kliminski, Elisheva Pokroy-Shapira, Shirly Oren, Ariela Dortort Lazar, Yael Pri-Paz Basson, Mohammad Egbaria, Yair Molad, Yonatan Edel, Vitaly Kliminski, Elisheva Pokroy-Shapira, Shirly Oren, Ariela Dortort Lazar, Yael Pri-Paz Basson, Mohammad Egbaria, Yair Molad

Abstract

Background: Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is an innate-immune receptor found in blood. Its presence reflects innate immune cell activation. We sought to investigate plasma sTREM-1 levels in patients with primary antiphospholipid syndrome (PAPS).

Methods: A cross-sectional, case-control design was used. Plasma sTREM-1 levels were analyzed by enzyme-linked immunosorbent assay (ELISA) in consecutive patients diagnosed with PAPS or asymptomatic antiphospholipid antibody (APLA) carriers and controls.

Results: The study cohort included 33 patients with PAPS, 10 asymptomatic APLA carriers, and 73 controls. Mean plasma sTREM-1 levels were significantly higher in patients with PAPS (299.2 ± 146.7 pg/ml) and thrombotic PAPS-ever (current and past thrombotic event) (327.2 ± 151.3 pg/ml) compared with controls (230.2 ± 85.5 pg/ml; p = 0.006 and p = 0.003, respectively), patients with thrombotic PAPS compared with patients with past obstetric APS (195.12 ± 58.52 pg/ml, p = 0.01) and APLA carriers (215.8 ± 51.6 pg/ml, p = 0.02), patients with current thrombotic PAPS (429.5 ± 227.5 pg/ml) compared with patients with past thrombotic PAPS (289.5 ± 94.65 pg/ml, p = 0.01), and patients with PAPS who had ever had a stroke or venous thromboembolic event compared with patients who had not (p = 0.007 and p = 0.02, respectively). On receiver operator characteristic curve analysis, plasma sTREM-1 levels differentiated patients with current thrombotic PAPS from asymptomatic APLA carriers and controls, with an area under the curve of 0.7292 (p = 0.0014) and 0.88 (p < 0.0001), respectively. Multivariate regression analysis to identify sTREM-1 predictors (thrombotic PAPS-ever, age, and sex) yielded an independent association of sTREM-1 levels with thrombotic PAPS (p < 0.0001).

Conclusions: Plasma sTREM-1 levels are significantly elevated in patients with thrombotic PAPS. Levels of sTREM-1 might serve as a biomarker for thrombosis in patients with PAPS.

Keywords: Antiphospholipid syndrome; Biomarker; Thrombosis; Triggering receptor expressed on myeloid cells-1 (TREM-1).

Conflict of interest statement

Ethics approval and consent to participate

The study protocol was reviewed and approved by the local Institutional Review Board, and all participants provided written informed consent.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Levels of plasma soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in patients with thrombotic primary antiphospholipid syndrome (PAPS)-ever (current and past thrombotic event) (n = 26) compared with healthy controls (n = 73) (p = 0.0003). Data are shown as box plots. Each box represents the 25th to 75th percentiles. Lines inside the boxes represent the median. Whiskers indicate the observations directly above the lower fence or below the lower fence, where the fence is defined as 1.5 × interquartile range
Fig. 2
Fig. 2
Levels of plasma soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in patients with thrombotic primary antiphospholipid syndrome (PAPS)-ever (current and past thrombotic event) (n = 26) compared with asymptomatic antiphospholipid antibody (APLA) carriers (n = 10) (p = 0.02). Data are shown as box plots. Each box represents the 25th to 75th percentiles. Lines inside the boxes represent the median. Whiskers indicate the observations directly above the lower fence, or below the lower fence, where the fence is defined as 1.5 × interquartile range
Fig. 3
Fig. 3
Plasma soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) level in patients with thrombotic PAPS (n = 26): comparison of current (n = 19) vs. past thrombotic evet (n = 7) (p = 0.01)
Fig. 4
Fig. 4
Plasma soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) level correlated with elevated erythrocyte sedimentation rate (ESR; r = 0.4, p = 0.009) and elevated serum high-sensitive C-reactive protein (hsCRP) level in patients with PAPS (r = 0.4, p = 0.02)
Fig. 5
Fig. 5
Receiver operating characteristic (ROC) curve of plasma sTREM-1 levels in patients with PAPS (n = 33) compared with asymptomatic persistent APLA carriers (n = 10) and healthy controls (n = 73). AUC was 0.73 (95% CI 1.003–1.013, p = 0.0014)
Fig. 6
Fig. 6
Receiver operating characteristic curve of plasma sTREM-1 levels in patients with current thrombotic PAPS (n = 7) compared with asymptomatic persistent APLA carriers (n = 10) and healthy controls (n = 73). Area under the curve (AUC) was 0.88 (95% CI 0.686–0.977, p < 0.0001)

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