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. 2018 Dec 18;9:2998. doi: 10.3389/fimmu.2018.02998

Table 1.

Summary of the different costimulatory pathway molecules data in SSc.

Costimulatory pathway Tissue expression Expression levels Clinical manifestations Experimental blockade in SSc animal models Experimental activation in SSc animal models Clinical trials Main results
Positive costimulators CD28-CD80/86 Serum Increased None None None
ICOS-B7RP1 Serum, skin Increased Early dcSSc None None
OX40L-OX40 Serum, skin Increased Early onset, worsening of dermal fibrosis Prevented and induced regression of established inflammation-driven dermal fibrosis in the bleomycin mouse model; Protected against interstitial lung disease and pulmonary hypertension in the Fra-2 model Spontaneous ILD Production of antiDNA antibodies
CD40L-CD40 Serum, skin Increased Digital ulcers, PH, early/active NVC pattern None None
CD112/155-DNAM-1 Skin Increased Correlates with more severe dermal fibrosis and ILD None None
Negative costimulators CTLA-4-CD80/86 Serum Increased dcSSc, correlates with disease activity and severity None Prevented induced dermal fibrosis; was effective in the treatment of established fibrosis 1) Pilot study evaluating the clinical and molecular effects of Abatacept in dcSSc
2) Study of Subcutaneous Abatacept to Treat Diffuse Cutaneous Systemic Sclerosis (ASSET) trial (ClinicalTrials.gov identifier: NCT02161406)
1) Trend toward improvement in mRSS
2) Estimated study completion date: September 2018
PD1-L-PD1 Serum Increased Correlates with disease severity None None

CD (cluster of differentiation), ICOS (inducible co-stimulatory molecule), B7RP1 (B7-related protein-1), DNAM-1 (DNAX Accessory Molecule-1), CTLA-4 (cytotoxic Tlymphocyte-associated protein 4), PD1 (programmed death 1), dcSSc (diffuse cutaneous systemic sclerosis), PH (pulmonary hypertension), NVC (nailfold vascular capillaroscopy), ILD (interstitial lung disease), mRSS (modified-Rodnan skin score)