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Abstract
Purpose Immune inhibitory receptors are important in maintaining immune homeostasis and preventing autoimmunity. We recently showed that the function of immune inhibitory CD200 Receptor (CD200R) changes in systemic lupus erythematosus (SLE) patients. In a subset of SLE patients, CD200R function switches from inhibiting to potentiating Toll-like receptor (TLR)-7/8-induced interferon gamma production. In this study, we aim to clarify the role of CD200 in the pathophysiology of systemic autoimmune disease and study its potential as a marker for disease. We investigate the expression of CD200R and its ligand CD200 in SLE and other interferon related systemic autoimmune diseases. In addition, we determine the concentration of soluble CD200 (sCD200) in systemic autoimmune disease. sCD200 can be both a functional ligand for CD200R, or a decoy ligand that competes for CD200R binding with cell-bound CD200. Lastly, we correlated sCD200 and sCD200R with disease manifestations in SLE patients.
Methods We studied CD200R and CD200 expression in patients with SLE, antiphospholipid syndrome (APS), primary Sjögren’s syndrome (pSS), and systemic sclerosis (SSc). We determined CD200 and CD200R expression in different cell subsets with flow cytometry. In addition, we measured sCD200 and sCD200R with ELISA in serum from SLE patients, and correlated concentrations with clinical disease manifestations.
Results We found an increased CD200R expression on monocytes of patients with SLE compared to healthy donors, while CD200 expression is decreased. CD200R expression is increased on T-cells and granulocytes from SLE, pSS and APS patients compared to healthy donors.
In addition, sCD200 concentration is elevated in serum from patients with SLE and APS compared to serum from healthy donors. sCD200 positively correlates with anti-dsDNA concentrations in SLE patients (r=0.45, p 0.002), but not with SLEDAI, renal involvement or complement (C3/C4) concentrations.
Soluble (s)CD200 concentration is increased in serum from patients with SLE and APS compared to healthy donor serum. *p<0.05, **p<0.005
Conclusions CD200R expression is increased on monocytes, T cells and granulocytes of SLE patients and other interferon-related auto-inflammatory diseases. sCD200 concentration in serum was increased in SLE and APS patients, which correlates with anti-dsDNA concentrations in SLE.
Our study shows that differences in CD200/CD200R expression are not specific for SLE, but present in other interferonopathies. Therefore, they might be related to common underlying disease mechanisms in systemic autoimmunity. For future studies, it would be of interest to investigate the CD200R:CD200 axis in relation to the interferon signature, or formation of neutrophil extracellular traps (NETs).
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