title: Serum BAFF concentrations in patients with Graves' disease and orbitopathy before and after immunosuppressive therapy.
abstract: BACKGROUND
  B cells are known to play a key role in the pathogenesis of autoimmune disease. B lymphocyte activating factor (BAFF), a member of TNF family, promotes autoantibody production by increasing B cell survival and proliferation. Serum BAFF concentrations have been found to be increased in systemic lupus erythematosus, rheumatoid arthritis, and Sjogren's syndrome.
  
  
  OBJECTIVE
  We have measured serum BAFF concentrations in patients with Graves' disease (GD) with or without Graves' orbitopathy (GO) and in active GO in relation to immunosuppressive treatment.
  
  
  METHODS
  Forty-two patients and nine normal controls were studied. Thirty-four patients had GO, which was active in 23. Of these, nine were treated with rituximab (RTX) and 14 with i.v. methylprednisolone (MP). Serum BAFF concentrations were measured at baseline in all patients, at peripheral B cell depletion and repopulation after RTX, and after therapy with MP.
  
  
  RESULTS
  Serum basal BAFF concentrations in GD patients were significantly higher when compared with normal controls (P = 0.0001), and no difference was observed in those with active or inactive GO. Serum BAFF concentrations were also significantly correlated with serum antithyroglobulin antibodies (P = 0.04) but not with sex, age, smoking habits, therapy for thyroid disease, and serum antithyroperoxidase antibodies and TSH receptor antibodies. After RTX, there was an increase of serum BAFF concentrations at the time of B cell depletion (P = 0.02) but also at B cell repopulation (P = 0.04). In patients treated with MP, serum BAFF concentrations decreased significantly after therapy (P < 0.01).
  
  
  CONCLUSIONS
  We report that serum BAFF concentrations are elevated in patients with GD, in whom hyperthyroidism is known to be based on a B-cell-driven pathophysiological mechanism. In active GO, BAFF further increases after therapy with RTX as a consequence of the B cell depletion per se. The decrease of serum BAFF after iv steroids suggests that MP may exert an immunosuppressive effect by modifying B-cell-derived immune reactions.
authors.affiliation: Endocrine Unit, Department of Medical Sciences, University of Milan and Fondazione Cà Granda Istituto di Ricovero e Cura a Carattere Scientifico, 20122 Milan, Italy.
authors.forename: Guia
authors.initials: G
authors.lastname: Vannucchi
authors.forename: Danila
authors.initials: D
authors.lastname: Covelli
authors.forename: Nicola
authors.initials: N
authors.lastname: Currò
authors.forename: Davide
authors.initials: D
authors.lastname: Dazzi
authors.forename: Antonia
authors.initials: A
authors.lastname: Maffini
authors.forename: Irene
authors.initials: I
authors.lastname: Campi
authors.forename: Paola
authors.initials: P
authors.lastname: Bonara
authors.forename: Claudio
authors.initials: C
authors.lastname: Guastella
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pignataro
authors.forename: Roberto
authors.initials: R
authors.lastname: Ratiglia
authors.forename: Paolo
authors.initials: P
authors.lastname: Beck-Peccoz
authors.forename: Mario
authors.initials: M
authors.lastname: Salvi
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D053264:B-Cell Activating Factor / Q000097:blood*; D001402:B-Lymphocytes / Q000187:drug effects*; D005260:Female; D006111:Graves Disease / Q000097:blood* / Q000188:drug therapy*; D049970:Graves Ophthalmopathy / Q000097:blood / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D053264:B-Cell Activating Factor; D007166:Immunosuppressive Agents; C505719:TNFSF13B protein, human; D000069283:Rituximab; D008775:Methylprednisolone