Serum Level of Soluble CD226 Receptor in Healthy Individuals is Highly Variable and Associated with Age

CD226 (DNAM-1) is a molecule that has been recently given a great deal of attention due to its immunomodulatory properties and possible usefulness in assessment of tumors and autoimmune disorders activity. This cellular transmembrane activating immunoreceptor is expressed predominantly on the surface of natural killer cells, most CD4+ T cells and CD8+ T cells, platelets, and monocytes (1). CD226, also known as DNAM-1 (DNAX Accessory Molecule-1), was originally described as an adhesion molecule that controls NK cell-mediated cytotoxicity (2). CD226 is also speculated to be an important suppressor of autoimmune responses (3). Single nucleotide polymorphism (rs763361) in CD226 gene, which leads to one amino acid substitution (Gly307Ser) in CD226, was reported to be associated with the development of several autoimmune diseases, including type 1 diabetes (T1D), multiple sclerosis, autoimmune thyroid disease (AITD) and rheumatoid arthritis (RA) (3). Interestingly, we and others reported that patients with distal 18q deletion syndrome - a natural model of CD226 haploinsufficiency, seem to be at higher risk of developing autoimmune conditions including T1D, AITD or vitiligo, coexisting with antibody and T regulatory cells deficiency (4). Membrane CD226 (mCD226) expressed on peripheral blood mononuclear cells might be shed from cell membranes by certain proteases and appear in the serum in its soluble (sCD226) form (5,6). There is a substantial body of evidence showing that sCD226 affects the interaction between CD226 and its ligands, resulting in modulation of CD226-mediated immune responses (7).