Elevated serum and cerebrospinal fluid levels of soluble human herpesvirustype 6 cellular receptor, membrane cofactor protein, in patients with multiple sclerosis

Membrane cofactor protein (CD46) is a member of a family of glycoproteins t hat are regulators of complement and prevent activation of complement on au tologous cells. Recently, CD46 has been identified as the cellular receptor for human herpesvirus Type 6 (HHV-6). Elevated levels of soluble CD46 have been described in several autoimmune disorders, and may be implicated in t he pathogenesis of these diseases. As several reports have supported an ass ociation of HHV-6 and multiple sclerosis, it was of interest to compare lev els of soluble CD46 in the sera of multiple sclerosis patients to that of h ealthy controls, other neurological disease controls, and other inflammator y disease controls. Using an immunoaffinity column comprised of immobilized monoclonal antibodies to CD46, serum levels of soluble CD46 were found to be significantly elevated in multiple sclerosis patients compared with heal thy and other neurological disease controls. Moreover, multiple sclerosis p atients who tested positive for HHV-6 DNA in serum had significantly elevat ed levels of soluble CD46 in their serum compared with those who were negat ive for HHV-6 DNA. A significant increase in soluble CD46 was also found in the serum of other inflammatory disease controls tested compared to health y controls. Additionally, a significant correlation was demonstrated betwee n levels of soluble CD46 in the serum and cerebrospinal fluid of multiple s clerosis patients. Collectively, these data suggest that elevated levels of soluble CD46 may contribute to the pathogenesis of inflammatory diseases, including multiple sclerosis.