Soluble Biomarkers for Prediction of Vascular and Gastrointestinal Disease Severity in Patients with Systemic Sclerosis.

Purpose of review: Disease severity biomarkers in patients with systemic sclerosis (SSc) provide an early and noninvasive screening tool to identify patients at increased risk for internal organ involvement that may impact diagnostic testing and treatment decisions. This review will focus on soluble SSc vascular and gastrointestinal disease biomarkers.

Recent findings: Due to high morbidity and mortality associated with SSc pulmonary hypertension, multiple biomarkers are currently under investigation including serum autoantibodies, chemistries [such as N-terminal pro-brain natriuretic peptide (NT-proBNP)], proteins [midkine (MDK) and follistatin-like 3 (FSTL3)], chemokines [C-X-C motif ligand 4 (CXCL4) and C-C motif ligand 21 (CCL21)], plasma growth factors [vascular endothelial growth factor (VEGF) and placental growth factor (PlGF)], cell adhesion molecules [vascular cell adhesion molecule 1 (VCAM-1)], and endothelial microparticles [CD144+ endothelial microparticle (CD144+ EMP)]. A subset of these have also been proposed as SSc digital ulcer biomarkers [anti-endothelin-1 type A receptor (anti-ETAR), PlGF, and NT-proBNP]. A combination of NT-proBNP and high sensitivity cardiac troponins T (hs-cTnT) and I (hs-cTnI) may be useful for assessing primary SSc cardiac involvement. Putative SSc renal disease biomarkers include VEGF and endostatin levels; while anti-U1 and U3 ribonucleoprotein (anti-U1- and anti-U3-RNP) antibodies and fecal-calprotectin (F-calprotectin) are associated with GI involvement.

Summary: Serum autoantibodies are the mainstay SSc severity biomarkers, but new biomarkers are under investigation.