title: Changes in macrophage function after rituximab treatment in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To assess changes in macrophage phenotype and function after rituximab-induced B cell depletion in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  10 patients with RA were treated with rituximab, achieving significant B cell depletion 4 months later. Clinical improvement, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, mRNA of B cell activating factor (BAFF), interleukin (IL) 10 and CD86 in human monocyte-derived macrophages (HMDMs) and tumour necrosis factor alpha (TNFalpha) secretion from cultured HMDMs were assessed at baseline and after the depletion.
  
  
  RESULTS
  A clinical response of American College of Rheumatology (ACR) 50% improvement was noted in six patients, and another two patients responded with moderate improvement, equivalent to ACR 20-50% improvements. RF and anti-CCP antibodies were positive at baseline in seven of ten patients. RF disappeared or declined in six patients 4 months after treatment, correlating with clinical improvement. By contrast, anti-CCP remained unchanged in six patients. After rituximab treatment, and in association with clinical improvement, BAFF, IL10 and CD86 mRNA expression in HMDM were significantly upregulated compared with values at baseline. A significant decrease in TNFalpha in the supernatant of cultured HMDM was also noted.
  
  
  CONCLUSIONS
  In addition to B cell depletion and attenuation in some of the specific autoantibodies, clinical improvement in rituximab-treated patients with RA occurred in association with changes in macrophage function.
authors.affiliation: Division of Clinical Immunology and Allergy, Bnai Zion Medical Center, P O Box 4940, Haifa 31048, Israel. elias.toubi@b-zion.org.il
authors.forename: E
authors.initials: E
authors.lastname: Toubi
authors.forename: A
authors.initials: A
authors.lastname: Kessel
authors.forename: G
authors.initials: G
authors.lastname: Slobodin
authors.forename: N
authors.initials: N
authors.lastname: Boulman
authors.forename: E
authors.initials: E
authors.lastname: Pavlotzky
authors.forename: D
authors.initials: D
authors.lastname: Zisman
authors.forename: M
authors.initials: M
authors.lastname: Rozenbaum
authors.forename: I
authors.initials: I
authors.lastname: Rosner
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D053264:B-Cell Activating Factor / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000187:drug effects; D051940:B7-2 Antigen / Q000096:biosynthesis; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D012217:Rheumatoid Factor / Q000097:blood; D000069283:Rituximab; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D001323:Autoantibodies; D053264:B-Cell Activating Factor; D051940:B7-2 Antigen; D010456:Peptides, Cyclic; D014409:Tumor Necrosis Factor-alpha; C487763:cyclic citrullinated peptide; D016753:Interleukin-10; D000069283:Rituximab; D012217:Rheumatoid Factor