Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2013) 32 MTE6 | DOI: 10.1530/endoabs.32.MTE6

ECE2013 Meet the Expert Sessions (1) (16 abstracts)

New immunotherapy approaches for Graves’ orbitopathy

Mario Salvi 1,

1Graves’ Orbitopathy Center, Endocrinology, Fondazione Ca’ Granda Irccs, Milan, Italy; 2Department of Clinical and Community Sciences, University of Milan, Milan, Italy.

The role of B-cell in human autoimmune disease have recently been emphasized due to the therapeutic benefit of B-cell depleting therapies. B cells are involved in the production of autoantibodies, CD4+T-cell activation and control of T-cell function and inflammation, through cytokine production. Although autoantibodies alone may not initiate autoimmune disease, their relationship with the disease course suggests that they are a key factor contributing to the mechanisms of disease pathogenesis. B cells are also important antigen presenting cells? Rituximab (RTX) has been used off-label in various autoimmune disorders and effectively depletes mature and memory CD20+B cells, but not long-lived plasma cells. This has provided the rationale for the use in Graves’ disease (GD), since blockade of pathogenic autoantibody generation might induce Graves’ hyperthyroidism remission. Although we suggest caution in proposing RTX as a novel therapeutic tool in this disease, preliminary data collected by us and others show that RTX does significantly affect the inflammatory activity and severity of GO. Recently, we have reported that low dose of RTX (100 mg), about 20-fold less than the commonly administered dose, caused effective peripheral B cell depletion and induced long term remission of GO, without further treatment. The amelioration of GO has not been different from what has been reported with larger doses of RTX. This study is potentially interesting also from the point of view of the safety concerns when using higher doses of a potent immunosuppressive agent like RTX. We envisage that the optimal strategy for controlling the progression of a disease like GO would be to pursue B-cell depletion shortly after diagnosis and not solely as additional therapy when standard immunosuppression has failed.

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