CD200 is a novel immuno-effective molecule, both cell membrane-bound and also existing in a soluble form in serum (sCD200), which acts to regulate inflammatory and acquired immune responses through interaction with cell-bound ligands, CD200R [12
]. We investigated soluble CD200, which can also be linked to apoptosis and is an immuno-effective ligand [13
]. In a murine model of passive cutaneous anaphylaxis, cross-linking of CD200R1 in vivo
produced profound suppression, greater than that seen following in vitro
CD200R1 activation, which it was felt might reflect higher constitutive expression of CD200R1 on mast cells in vivo
compared with cells maintained in culture, and/or the existence of other cell-cell interactions in vivo
, which could lower the threshold for CD200R1-mediated suppression. Regardless, these data were taken to imply a potential clinical utility for CD200-CD200R1 in regulation of allergic inflammatory disease [14
Psoriasis vulgaris is one of the most prevalent chronic, inflammatory skin disorders. This skin condition is histologically characterized by abnormal proliferation of keratinocytes and infiltration of immune cells, predominantly T cells and dendritic cells in psoriatic lesions. The majority of inflammatory cells and cytokines remain in the tissue, and a relatively small proportion can be measured in the peripheral blood, including interleukins, which have shown to be elevated in patients with cardiovascular disease, metabolic syndrome, and diabetes [15
]. Pemphigus vulgaris is widely believed to result from the deleterious action of autoantibodies directed against desmoglein 1 and desmoglein 3, resulting in loss of cell–cell adhesion within the epidermis and increased cell apoptosis [17
The discovery of new immunological factors and a better understanding of these disorders could help to develop new biomarkers and biological drugs against specific immunological elements that cause psoriasis and pemphigus [18
]. In our study, there was a power correlation between CD200 levels and clinical severity, suggesting that CD200 could be of potential importance as a biomarker of autoimmune and inflammatory skin disorders. Kouno et al. [20
] showed that targeted therapy is feasible and may be useful for hyperproliferative and inflammatory skin diseases. They chose TRAIL as a biological model because it inhibits activated lymphocytes and causes apoptosis of hyperproliferative keratinocytes, which are features of various skin diseases. Our study showed that CD200 could play a role in maintaining pro-inflammatory reactions or immune tolerance in autoimmune and inflammatory skin disorders. Taken together, the findings of our study and previous investigations suggest the therapeutic potential of CD200 targeting agents in the treatment of skin disorders such as psoriasis, pemphigus, and bullous pemphigoid.
In our previous study, we reported the case of a man with pruritic bullous pemphigoid and very high levels of total IgE (5000 kU/L) who was refractory to the aggressive immunosuppressive regimens (systemic steroids, daily cyclophosphamide) for BP but who responded rapidly to systemic anti-IgE (omalizumab). The circulating level of sCD200 was 48.45 pg/mL in serum and 243 pg/mL in blister fluid. SCD200 levels were higher in blister fluid than in serum. During the second month of follow-up, the patient’s sCD200 level decreased to 26.7 pg/mL. After the second round of omalizumab (300 mg), the frequency of exacerbations decreased [8
]. Reduction in serum levels CD200 with anti-IgE treatment suggests that CD200 could be pro-inflammatory [3
]. In the current study, we found the highest CD200 levels circulating in the pemphigus patients. High levels of serum soluble CD200 affect CD200R and try to protect tissue damage during autoimmune responses. In fact, the significantly higher values in psoriasis vulgaris than in pemphigus vulgaris patients and healthy controls could also support the pro-inflammatory effect.