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Complement alternative pathway dysregulation seems to be the pathophysiological basis of Dense Deposit Disease (DDD). Here, we describe a monoclonal anti-factor H (FH) autoantibody in a woman diagnosed with DDD with a monoclonal gammapathy. Enzyme-linked immunosorbent assays evidenced the presence of anti-FH antibodies in the patient's serum and showed that they were associated with the monoclonal IgG-λ fraction. These autoantibodies recognize the N-terminal region of FH and interfere with its regulatory function. In summary, in the DDD patient described here, the activation of complement alternative pathway was favoured by the presence of anti-FH autoantibodies that recognize the regulatory region of this protein and impede its function and which could ultimately cause the glomerulopathy.

Anti-factor H antibody affecting factor H cofactor activity in a patient with dense deposit disease