Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2009) 20 P68

ECE2009 Poster Presentations Thyroid (117 abstracts)

Treatment of patients with Graves’ orbitopathy (GO) with rituximab: effects on humoral immunity

Guia Vannucchi 1 , Irene Campi 1 , Marco Bonomi 2 , Nicola Currò 3 , Davide Dazzi 1 , Danila Covelli 1 , Paola Bonara 4 , Luca Persani 2 , Jack Wall 5 , Paolo Beck-Peccoz 1 & Mario Salvi 1


1Endocrine Unit, Department of Medical Sciences, Fondazione Policlinico IRCCS, University of Milan, Milan, Italy; 2Istituto Auxologico, Milan, Italy; 3Ophthalmology, Fondazione Policlinico IRCCS, Milan, Italy; 4Internal Medicine, Fondazione Policlinico IRCCS, Milan, Italy; 5University of Sidney, Sidney, Australia.


Rituximab (RTX) is a monoclonal antibody which binds CD20 antigen and induces B cell depletion. It is not known if its therapeutic effect in autoimmune diseases is mediated by modifications of the humoral immune response, namely the antibody production. Aim of the present study was to evaluate the effect of RTX on serum TSH-receptor antibodies, both binding (TBII) and stimulating (TSAb) and on serum antibodies against three orbital antigens, calsequestrin, XIII collagen and the flavoprotein subunit of succinate dehydrogenase (FP-SDH). Nine patients, 7 with active GO and 2 with only lid signs have been treated with two infusions of RTX at two week-interval with a follow-up of 50 weeks. At each visit patients were assessed by measuring peripheral blood lymphocytes count, thyroid function, TBII and TSAb and the antibodies anti-orbit. The ophthalmological evaluation aimed at defining the disease activity (CAS) and severity (NOSPECS). TSAb serum activity was tested in a CHO-TSHR stable cell line. Cells were incubated with 5% serum in hypotonic medium and cAMP accumulation was determined by RIA. The anti-orbit antibodies were measured by ELISA. We did not observe significant reduction of TRAb in relation to peripheral B cell depletion (P=NS) and to the clinical activity of GO (P=NS); TRAb had a slight significant negative correlation with time (P<0.01) due to the attainment of euthyroidism in all patients at the end of follow-up. Serum TSAb did not change after RTX therapy and significantly correlated with serum TRAb concentrations (P<0.0001). Finally, no significant changes of serum anti-orbit antibodies were observed at each time of the follow-up (P=NS). In conclusion, the effect of RTX in GO does not seem to be mediated by changes of anti-thyroid and anti-orbit antibody production. It is reasonable to hypothesize that the effect of RTX is mediated through the pathway of B cell antigen presentation.

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