Elevated serum levels of soluble membrane cofactor protein (CD46, MCP) in patients with systemic lupus erythematosus (SLE)

Abstract

SUMMARYMembrane cofactor protein (MCP, CD46) is a cell surface complement regulatory protein which acts as a cofactor for the factor I-mediated cleavage of the activated complement components C3b/C4b. To evaluate the clinical usefulness of serum soluble CD46 as a marker of disease activity in patients with SLE, serum levels of sCD46 were measured by ELISA, using two MoAbs (M160 and M177), each of which recognized two different epitopes on CD46 molecule in SLE, other autoimmune diseases and healthy controls. Serum sCD46 levels in active SLE patients (30´5 6 14´1 ng/ml) were signi®cantly higher than those of inactive SLE (5´8 6 7´1 ng/ml; P 0´0003), rheumatoid arthritis (14´9 6 11´6 ng/ ml; P 0´0218), primary Sjo Ègren's syndrome (12´3 6 11´6 ng/ml; P 0´0039) and normal controls (7´3 6 3´6 ng/ml; P 0´0005). The elevated serum sCD46 levels in active SLE patients signi®cantly decreased from 30´5 6 14´1 ng/ml to 8´0 6 6´3 ng/ml after effective corticosteroid and immunosuppressant therapy (P 0´018). Additionally, we found a signi®cant negative association between increasing concentration of sCD46 and decreasing levels of CH50 in SLE (r ±0´598, P 0´0009). These results suggest that sCD46 re¯ects in vivo activation of complement system and provides an additional useful serum parameter of active SLE.

Urine Levels of CD46 (Membrane Cofactor Protein) Are Increased in Patients with Glomerular Diseases

“…Another report (29) has suggested that tubular MCP is overexpressed at the deposition site of the membrane attack complex. The levels of sMCP were increased in patients with malignancy (19) and autoimmune diseases such as systemic lupus erythematosus (30). Our present results may support previous findings suggesting that levels of MCP expression are increased in some cell lines by cytokines and inflammation (31,32).…”

CD46 Contributes to the Severity of Group A Streptococcal Infection

“…5), whereas there was no growth difference in serum from these mice (data not shown), indicating that human CD46 facilitates bacterial survival and suggesting that the binding of CD46 might help the bacteria to survive host defenses. It was shown that soluble CD46 is present in normal human plasma (18) and that CD46 levels are elevated under autoimmune conditions (12,25). To investigate the importance of CD46 in human blood, we pre- (10 7 CFU) in lag, early log, mid-log, or stationary phase was incubated for 2 h with MBP-CD46 or MBP (control).…”

IFN-α and CD46 stimulation are associated with active lupus and skew natural T regulatory cell differentiation to type 1 regulatory T (Tr1) cells

“…2C), skews nTregs and Tconv to Tr1 secreting IL-10, which prematurely imbalances the adaptive immunity toward immune suppression. The role of C3b protein, the CD46 agonist resulting from C′ activation, in the pathogenesis of active lupus patients is also suggested by the presence in the serum of these patients of soluble CD46 (30), product of proteolytic cleavage of apoptotic cell membranes (31). As for IFN-α, by reducing nTreg and Tconv number and function, this cytokine may further enhance the risk of autoimmunity and infection.…”