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Activation of the Classical Pathway of Complement by Non‐Immune Complexes of Immunoglobulins with Human Protein Fv (Fv Fragment‐Binding Protein)
Author(s) -
RUFFET E.,
PIRÈS R.,
PILLOT J.,
BOUVET J.P.
Publication year - 1994
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.1994.tb03474.x
Subject(s) - antibody , complement system , classical complement pathway , complement c1q , microbiology and biotechnology , protein g , protein a/g , chemistry , biology , protein a , immunology , fusion protein , biochemistry , recombinant dna , gene
Protein Ev, 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 nonimmune 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 Ev‐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 buman 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 mimicks antigen‐antibody reactions, and suggest its involvement in hepatitis‐associated vasculitis and in local lesions of some infiammatory gut diseases.