Rituximab treatment in patients with active Graves' orbitopathy: Effects on proinflammatory and humoral immune reactions

G. Vannucchi, I. Campi, M. Bonomi, D. Covelli, D. Dazzi, N. Currò, S. Simonetta, P. Bonara, L. Persani, C. Guastella, J. Wall, P. Beck-Peccoz, M. Salvi

Research output: Contribution to journalArticle

Abstract

Summary 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.

Original languageEnglish
Pages (from-to)436-443
Number of pages8
JournalClinical and Experimental Immunology
Volume161
Issue number3
DOIs
Publication statusPublished - Sep 2010

Keywords

  • CD20
  • Cytokines
  • Graves'orbitopathy
  • Rituximab
  • TSH-receptor antibodies

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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