In active Graves' orbitopathy (GO), proinflammatory cytokines predominate. Circulating thyroid stimulating hormone (TSH)-receptor antibodies (TRAb) have been correlated with GO clinical activity and severity. In preliminary studies rituximab (RTX), an anti-CD 20 monoclonal antibody, has induced clinical improvement of active GO without a change in serum anti-thyroid antibodies. We have studied whether RTX in GO acts by affecting proinflammatory cytokines and thyroid and orbital-directed antibodies. Ten patients with GO were treated with RTX, administered twice intravenously (i.v.) (1000 mg) at days 1 and 15, and 20 with methylprednisolone, administered weekly i.v. (500 mg), for 16 weeks. Patients were studied before treatment, at B cell depletion and at 4, 8, 16, 20, 30 and 50 weeks. Peripheral lymphocytes, serum interleukin (sIL)-6, sIL-6r, chemokine (C-X-C motif) ligand 10 (CXCL10), TRAb and stimulating antibodies (TSAb) and autoantibodies against orbital calsequestrin, collagen XIII and flavoprotein subunit of succinate dehydrogenase (FP-SDH) were measured at baseline and after treatment. Serum IL-6 and sIL-6R concentrations did not change after RTX [P = not significant (n.s.)]. Serum CXCL10 increased after RTX at B cell depletion and at 30 weeks (P < 0·003). Serum TSAb did not change in relation to TRAb, nor did antibodies against orbital antigens (P = n.s.). In conclusion, this study shows that RTX in GO does not affect humoral reactions. The observed increase of serum CXCL10 concentrations at B cell depletion may result from cell lysis. We suggest that RTX may exert its effect in GO by inhibiting B cell antigen presentation.
Rituximab treatment in patients with active Graves' orbitopathy : effects on proinflammatory and humoral immune reactions / G.M. Vannucchi, I. Campi, M. Bonomi, D. Covelli, D. Dazzi, N. Currò, S. Simonetta, P. Bonara, L. Persani, C. Guastella, J. Wall, P.L.M. Beck Peccoz, M. Salvi. - In: CLINICAL AND EXPERIMENTAL IMMUNOLOGY. - ISSN 0009-9104. - 161:3(2010 Sep), pp. 436-443.
|Titolo:||Rituximab treatment in patients with active Graves' orbitopathy : effects on proinflammatory and humoral immune reactions|
|Parole Chiave:||CD20; cytokines; Graves’orbitopathy; rituximab; TSH-receptor antibodies|
|Settore Scientifico Disciplinare:||Settore MED/31 - Otorinolaringoiatria|
Settore MED/13 - Endocrinologia
Settore MED/30 - Malattie Apparato Visivo
|Data di pubblicazione:||set-2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/j.1365-2249.2010.04191.x|
|Appare nelle tipologie:||01 - Articolo su periodico|