title: Treatment of Graves' disease with rituximab specifically reduces the production of thyroid stimulating autoantibodies.
abstract: Treatment of Graves' disease (GD) with the B-lymphocyte depleting agent rituximab in addition to standard methimazole-therapy prolongs remission. Paradoxically, it does not mediate a reduction in thyrotropin receptor antibody (TRAb) levels over that of methimazole monotherapy. Using a bioassay involving Chinese hamster ovary cells transfected with the human thyrotropin receptor, we found that the stimulatory capacity of TRAbs was reduced markedly, by 66+/-22%, upon treatment with rituximab and methimazole for 21 days (p<0.0001), compared to an increase by 33% on average (NS) in patients receiving methimazole alone (p=0.04 between groups). The overall levels of TRAbs decreased by around 15% in both groups. Within one year of follow-up, rituximab therapy mediated specific decreases in thyroid-peroxidase antibody- and IgM levels, whereas IgG levels were unaffected. The data indicate that rituximab therapy has differential effects on pathogenic and non-pathogenic autoantibodies, even when directed against the same antigen. The possible mechanisms underlying this hitherto unappreciated phenomenon are discussed.
authors.affiliation: Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark. Fassi@dadlnet.dk
authors.forename: Daniel
authors.initials: D
authors.lastname: El Fassi
authors.forename: J Paul
authors.initials: JP
authors.lastname: Banga
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Gilbert
authors.forename: Carolyn
authors.initials: C
authors.lastname: Padoa
authors.forename: Laszlo
authors.initials: L
authors.lastname: Hegedüs
authors.forename: Claus H
authors.initials: CH
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000917:Antibody Formation / Q000187:drug effects*; D001323:Autoantibodies / Q000097:blood; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D006111:Graves Disease / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating / Q000187:drug effects / Q000378:metabolism*; D007155:Immunologic Factors / Q000627:therapeutic use*; D000069283:Rituximab
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D018828:Immunoglobulins, Thyroid-Stimulating; D007155:Immunologic Factors; D000069283:Rituximab; D000242:Cyclic AMP