title: Abatacept reduces levels of switched memory B cells, autoantibodies, and immunoglobulins in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Abatacept (ABA) is a chimeric molecule, able to block the CD28-mediated costimulatory pathway. To evaluate the hypothesis that, through this mechanism of action, ABA may down-modulate the immune responses of B lymphocytes in rheumatoid arthritis (RA), we investigated the serum levels of immunoglobulins (Ig), free light chains (FLC), anticitrullinated protein antibodies (ACPA), and rheumatoid factor (RF), as well as the number of B lymphocytes differentiated into post-switch memory cells in patients treated with ABA.
  
  
  METHODS
  The serum levels of Ig, FLC, different ACPA, RF isotypes, and the B cell phenotype were longitudinally evaluated in 30 patients with RA treated with ABA.
  
  
  RESULTS
  At baseline, the proportion of total and post-switch memory B cells was lower in RA than in healthy individuals. After 6 months of ABA treatment we observed significant reductions of serum levels of IgG, IgA, and IgM, as well as FLC, with a normalization in many patients who had initially abnormal values. A significant reduction of the titers of IgG- and IgA-ACPA, as well as of IgM-, IgA-, and IgG-RF was also observed. A decrease of autoantibodies below the upper limits of normal values was found in 2 of 26 patients (8%) initially seropositive for IgG-ACPA, 1 of 14 (7%) for IgA-ACPA, 5 of 22 (23%) for IgM-RF, 7 of 22 (30%) for IgA-RF, and 5 of 16 (31%) for IgG-RF. After treatment, the proportion of circulating post-switch memory B cells was also further significantly decreased.
  
  
  CONCLUSIONS
  ABA treatment in patients with RA can reduce signs of polyclonal B cell activation, inducing a trend toward normalization of serum levels of different classes of Ig and of FLC, decreasing titers of ACPA and RF, and percentages of post-switch memory B cells.
authors.affiliation: From the Rheumatology Unit and Clinical Immunology, Spedali Civili, Brescia; and Clinical Biochemistry, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Scarsi
authors.forename: Lucia
authors.initials: L
authors.lastname: Paolini
authors.forename: Doris
authors.initials: D
authors.lastname: Ricotta
authors.forename: Antonio
authors.initials: A
authors.lastname: Pedrini
authors.forename: Silvia
authors.initials: S
authors.lastname: Piantoni
authors.forename: Luigi
authors.initials: L
authors.lastname: Caimi
authors.forename: Angela
authors.initials: A
authors.lastname: Tincani
authors.forename: Paolo
authors.initials: P
authors.lastname: Airò
mesh_terms: D000069594:Abatacept; D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D016009:Chi-Square Distribution; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage* / Q000276:immunology; D007136:Immunoglobulins / Q000032:analysis / Q000276:immunology*; D007156:Immunologic Memory / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012217:Rheumatoid Factor / Q000276:immunology / Q000378:metabolism; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D018796:Immunoconjugates; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D000069594:Abatacept; D012217:Rheumatoid Factor
keywords: ABATACEPT; ANTICITRULLINATED PROTEIN ANTIBODIES; B LYMPHOCYTES; FREE LIGHT CHAINS; RHEUMATOID FACTOR