Activation of the classical pathway of complement by non-immune complexes of immunoglobulins with human protein FV (FV fragment-binding protein).

Protein FV, a human sialoprotein recently described in the stools of patients suffering from liver diseases, binds the variable domain of the heavy chains of immunoglobulins. We show here that preincubation of this protein with monoclonal human IgG1 and IgM activates the complement cascade by forming non-immune complexes, as evidenced by haemolysis inhibition of antibody-coated sheep erythrocytes. As negative controls, no inhibition was observed after incubation either with immunoglobulins or with protein FV alone, and with the protein FV-depleted medium. Activation was due to the binding of immunoglobulins with protein FV, as shown by inhibition of protein FV-induced agglutination of the sensitized erythrocytes in the absence of complement. Activation of the classical pathway was demonstrated both by using a human IgG4 or F(ab')2 fragments unable to activate C1q, and by Western blot analysis of the cleavage of C4 in human serum. These results confirm that protein FV-binding mimics antigen-antibody reactions, and suggest its involvement in hepatitis-associated vasculitis and in local lesions of some inflammatory gut diseases.