Increased soluble CD200 in serum of SLE patients does not reflect disease activity or affect CD200R1 function in T cells

CD200 receptor 1 (CD200R) is an inhibitory immune receptor that is functionally altered in people with the interferonopathy systemic lupus erythematosus (SLE): soluble CD200 is increased in serum, and on monocytes CD200R stimulates inflammation in SLE patients. However, CD200R is not studied on T cells in SLE. Here we assessed CD200R expression on immune cells, function on T cells, and whether sCD200 in serum correlates with diseases activity in SLE. In a cross-sectional cohort study with SLE, antiphospholipid syndrome, primary Sjögren’s syndrome, and systemic sclerosis we measured CD200R and CD200 membrane expression using flowcytometry, and determined soluble CD200R (sCD200R) and CD200 (sCD200) concentrations in serum. In a prospective cohort study in 100 patients with SLE with a two-year follow-up, we collected consecutive serum and urine samples, and correlated soluble CD200R and CD200 to disease activity. CD200R expression was increased on T cells from SLE patients compared to controls, but not in other interferonopathies. Ligation of CD200R in vitro inhibited cytokine production by T cells from controls as well as from SLE patients. In SLE patients, concentrations of sCD200 were increased in circulation, while sCD200R concentrations were decreased. sCD200 was increased in patients with clinically active SLE, although there was no correlation with disease flares within patients. Our findings indicate that CD200R is a functional inhibitory receptor on T cells in SLE. In addition, we found that soluble CD200 in serum is increased in SLE but does not change during SLE flares. Together, considering the potential therapeutical benefit of agonizing inhibitory receptors in autoimmune disease, this makes CD200R an interesting target for treating SLE.