title: Changes in peripheral blood B cell subsets at diagnosis and after treatment with disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis: correlation with clinical and laboratory parameters.
abstract: OBJECTIVE
  To assess variation in peripheral blood B lymphocyte subsets in rheumatoid arthritis (RA).
  
  
  METHODS
  B lymphocyte subsets in disease-modifying anti-rheumatic drug (DMARD)-naïve patients with RA (n = 30), patients with RA treated with DMARDs (n = 73) and healthy controls (n = 46) were analyzed by flow cytometry. Total B cells, total memory B cells, immunoglobulin M (IgM) memory B cells, switched memory B cells, non-switched memory B cells, CD21lo B cells, transitional B cells and plasmablasts were measured. Correlation with clinical and laboratory parameters was performed.
  
  
  RESULTS
  Total memory B cells, IgM memory B cells and non-switched memory B cells were reduced in RA patients at diagnosis compared to controls (P < 0.05). In patients with treated RA, there was a further reduction of total B cells, CD21lo cells, transitional B cells and plasmablasts, compared to controls (P < 0.05). The reduction in absolute numbers of total B cells, switched memory B cells, CD21lo cells, transitional B cells and plasmablasts in treated RA patients was significant (P < 0.05) even when compared to the DMARD-naïve patients. Only treatment responders (Disease Activity Score < 3.2) had reduced total B cells and absolute numbers of switched and IgM memory B cells (P < 0.05). In patients requiring leflunomide, total memory B cells, IgM memory B cells, non-switched memory B cells and absolute numbers of switched memory B cells were reduced compared with the remainder of the patient group (P < 0.05).
  
  
  CONCLUSIONS
  There is reduction of various B cell subsets in RA patients at diagnosis. Treatment with DMARDs leads to further reduction in additional B cell subsets without correction of the abnormalities. Reduction in individual subsets may predict RA patients requiring more intensive therapy.
authors.affiliation: Division of Human Immunology, SA Pathology (IMVS), Adelaide, South Australia, Australia.|Immunology and Allergy Unit, Flinders Medical Centre, Bedford Park, Adelaide, South Australia, Australia.
authors.forename: Jeremy
authors.initials: J
authors.lastname: McComish
authors.affiliation: Division of Human Immunology, SA Pathology (IMVS), Adelaide, South Australia, Australia.
authors.forename: Joy
authors.initials: J
authors.lastname: Mundy
authors.affiliation: Discipline of Public Health, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Tom
authors.initials: T
authors.lastname: Sullivan
authors.affiliation: Rheumatology Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.|The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Susanna M
authors.initials: SM
authors.lastname: Proudman
authors.affiliation: Division of Human Immunology, SA Pathology (IMVS), Adelaide, South Australia, Australia.|Clinical Immunology Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors.forename: Pravin
authors.initials: P
authors.lastname: Hissaria
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents
keywords: B cell subsets; B cells; CCP/ACPA; disease-modifying anti-rheumatic drugs; flow cytometry; memory B cells; rheumatoid arthritis