title: BAFF and TACI gene expression are increased in patients with untreated very early rheumatoid arthritis.
abstract: OBJECTIVE
  B cells play important roles in rheumatoid arthritis (RA). Given the beneficial effect of B cell depletion therapy in RA as well as the observed alterations in B cell subpopulations in this disease, we evaluated whether changes in the expression of genes related to B cell survival and activation were already present in patients with untreated very early RA (VERA; < 6 weeks of disease duration).
  
  
  METHODS
  The expression of a group of B cell-related activation and survival genes was quantified in peripheral blood mononuclear cells from patients with VERA by real-time PCR and compared with untreated early RA (< 1 year), established treated RA, and other untreated early arthritis conditions. Serum B cell-activating factor belonging to the tumor necrosis factor family (BAFF) was quantified by ELISA.
  
  
  RESULTS
  BAFF gene expression and serum levels were highest in patients with VERA. The expression of BAFF receptor (BAFF-R) increased with disease progression, while transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) was elevated since the first weeks of RA onset. Paired box 5 gene expression was also increased at all RA stages. Chemokine (C-X-C motif) receptor 5 was elevated only in established RA. No differences were observed in B cell maturation antigen, activation-induced cytidine deaminase, B lymphocyte-induced maturation protein, and B cell lymphoma 2 expression.
  
  
  CONCLUSIONS
  Disturbances in the expression of B cell-related activation and survival genes, particularly BAFF and TACI, occur from the onset of RA and precede changes in BAFF-R. These alterations can lead to the development of autoreactive B cells from the first weeks of RA onset.
authors.affiliation: Rheumatology Research Unit, and the Cellular Immunology Unit, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Rita A
authors.initials: RA
authors.lastname: Moura
authors.forename: Helena
authors.initials: H
authors.lastname: Canhão
authors.forename: Joaquim
authors.initials: J
authors.lastname: Polido-Pereira
authors.forename: Ana M
authors.initials: AM
authors.lastname: Rodrigues
authors.forename: Márcio
authors.initials: M
authors.lastname: Navalho
authors.forename: Ana F
authors.initials: AF
authors.lastname: Mourão
authors.forename: Catarina
authors.initials: C
authors.lastname: Resende
authors.forename: Raquel
authors.initials: R
authors.lastname: Campanilho-Marques
authors.forename: João
authors.initials: J
authors.lastname: Madruga Dias
authors.forename: José Alberto Pereira
authors.initials: JA
authors.lastname: da Silva
authors.forename: Luis
authors.initials: L
authors.lastname: Graca
authors.forename: João E
authors.initials: JE
authors.lastname: Fonseca
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000473:pathology / Q000503:physiopathology*; D053264:B-Cell Activating Factor / Q000097:blood* / Q000235:genetics; D001402:B-Lymphocytes / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002470:Cell Survival / Q000502:physiology; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D053303:Transmembrane Activator and CAML Interactor Protein / Q000097:blood* / Q000235:genetics
chemical_list: D053264:B-Cell Activating Factor; D015415:Biomarkers; D012333:RNA, Messenger; C108467:TNFRSF13B protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein
keywords: B CELLS; BAFF; MESSENGER RNA; RHEUMATOID ARTHRITIS; TACI