title: Expression of BAFF receptors in muscle tissue of myositis patients with anti-Jo-1 or anti-Ro52/anti-Ro60 autoantibodies.
abstract: BACKGROUND
  Anti-Jo-1 and anti-Ro52 autoantibodies are common in patients with myositis, but the mechanisms behind their production are not known. Survival of autoantibody-producing cells is dependent on B-cell-activating factor of the tumour necrosis factor family (BAFF). BAFF levels are elevated in serum of anti-Jo-1-positive myositis patients and are influenced by type-I interferon (IFN). IFN-producing cells and BAFF mRNA expression are present in myositis muscle. We investigated expression of the receptors for BAFF in muscle tissue in relation to anti-Jo-1 and anti-Ro52/anti-Ro60 autoantibodies and type-I IFN markers.
  
  
  METHODS
  Muscle biopsies from 23 patients with myositis selected based on autoantibody profile and 7 healthy controls were investigated for expression of BAFF receptor (BAFF-R), B-cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI). Nineteen samples were assessed for plasma (CD138) and B-cell (CD19) markers. The numbers of positive cells per area were compared with the expression of plasmacytoid dendritic cell (pDC) marker blood dendritic cell antigen-2 (BDCA-2) and IFNα/β-inducible myxovirus resistance-1 protein (MX-1).
  
  
  RESULTS
  BAFF-R, BCMA and TACI were expressed in five, seven and seven patients, respectively, and more frequently in anti-Jo-1-positive and/or anti-Ro52/anti-Ro60-positive patients compared to controls and to patients without these autoantibodies (P = BAFF-R: 0.007, BCMA: 0.03 and TACI: 0.07). A local association of receptors with B and plasma cells was confirmed by confocal microscopy. The numbers of CD138-positive and BCMA-positive cells were correlated (r = 0.79; P = 0.001). Expression of BDCA-2 correlated with numbers of CD138-positive cells and marginally with BCMA-positive cells (r = 0.54 and 0.42, respectively; P = 0.04 and 0.06, respectively). There was a borderline correlation between the numbers of positively stained TACI cells and MX-1 areas (r = 0.38, P = 0.08).
  
  
  CONCLUSIONS
  The expression pattern of receptors for BAFF on B and plasma cells in muscle suggests a local role for BAFF in autoantibody production in muscle tissues of patients with myositis who have anti-Jo-1 or anti-Ro52/anti-Ro60 autoantibodies. BAFF production could be influenced by type-I IFN produced by pDCs. Thus, B-cell-related molecular pathways may participate in the pathogenesis of myositis in this subset of patients.
authors.forename: Olga
authors.initials: O
authors.lastname: Kryštůfková
authors.forename: Sevim
authors.initials: S
authors.lastname: Barbasso Helmers
authors.forename: Paulius
authors.initials: P
authors.lastname: Venalis
authors.forename: Vivianne
authors.initials: V
authors.lastname: Malmström
authors.forename: Eva
authors.initials: E
authors.lastname: Lindroos
authors.forename: Jiří
authors.initials: J
authors.lastname: Vencovský
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Lundberg
mesh_terms: D000328:Adult; D000368:Aged; D000974:Antibodies, Antinuclear / Q000276:immunology; D018941:Antigens, CD19 / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000096:biosynthesis; D053265:B-Cell Activation Factor Receptor / Q000096:biosynthesis*; D053301:B-Cell Maturation Antigen / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D001706:Biopsy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007370:Interferon Type I / Q000494:pharmacology; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism* / Q000473:pathology; D009220:Myositis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D012261:Ribonucleoproteins / Q000276:immunology; D053668:Syndecan-1 / Q000378:metabolism; D053303:Transmembrane Activator and CAML Interactor Protein / Q000096:biosynthesis*; D000099207:SS-A Antigen
chemical_list: D000974:Antibodies, Antinuclear; D018941:Antigens, CD19; D001323:Autoantibodies; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D007370:Interferon Type I; D012261:Ribonucleoproteins; D053668:Syndecan-1; D053303:Transmembrane Activator and CAML Interactor Protein; D000099207:SS-A Antigen; C046750:Jo-1 antibody; C108467:TNFRSF13B protein, human; C435926:TNFRSF13C protein, human; C086966:TNFRSF17 protein, human; C505719:TNFSF13B protein, human