Treatment of Graves' disease with rituximab specifically reduces the production of thyroid stimulating autoantibodies

TY - JOUR

T1 - Treatment of Graves' disease with rituximab specifically reduces the production of thyroid stimulating autoantibodies

AU - El Fassi, Daniel

AU - Banga, J Paul

AU - Gilbert, Jacqueline A

AU - Padoa, Carolyn

AU - Hegedüs, Laszlo

AU - Nielsen, Claus H

N1 - Keywords: Animals; Antibodies, Monoclonal; Antibody Formation; Autoantibodies; CHO Cells; Cricetinae; Cricetulus; Cyclic AMP; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Immunologic Factors

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

U2 - 10.1016/j.clim.2008.09.007

DO - 10.1016/j.clim.2008.09.007

M3 - Journal article

C2 - 18964302

SN - 1521-6616

VL - 130

SP - 252

EP - 258

JO - Clinical Immunology

JF - Clinical Immunology

IS - 3

ER -