INTRODUCTION: 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 IFNalpha/beta-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.
- MeSH
- Antigens, CD19 metabolism MeSH
- Antibodies, Antinuclear immunology MeSH
- Autoantibodies * immunology MeSH
- B-Lymphocytes metabolism drug effects MeSH
- Biopsy MeSH
- Adult MeSH
- B-Cell Activating Factor biosynthesis MeSH
- Immunohistochemistry MeSH
- Interferon Type I pharmacology MeSH
- Microscopy, Confocal MeSH
- Middle Aged MeSH
- Humans MeSH
- B-Cell Maturation Antigen * biosynthesis MeSH
- Myositis * immunology metabolism pathology MeSH
- B-Cell Activation Factor Receptor * biosynthesis MeSH
- Transmembrane Activator and CAML Interactor Protein * biosynthesis MeSH
- Ribonucleoproteins immunology MeSH
- Aged MeSH
- Muscles * metabolism pathology MeSH
- Syndecan-1 metabolism MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
OBJECTIVE: To investigate serum levels of B cell activating factor (BAFF) in patients with myositis and correlate these to autoantibody profile, clinical phenotype and treatment.
- MeSH
- Analysis of Variance MeSH
- Antibodies, Antinuclear blood MeSH
- Autoantibodies immunology blood MeSH
- C-Reactive Protein analysis MeSH
- Dermatomyositis drug therapy immunology blood MeSH
- Child MeSH
- Adult MeSH
- B-Cell Activating Factor blood MeSH
- Financing, Organized MeSH
- Glucocorticoids therapeutic use MeSH
- Creatine Kinase blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Myositis drug therapy immunology blood MeSH
- Statistics, Nonparametric MeSH
- Polymyositis drug therapy immunology blood MeSH
- Tumor Necrosis Factor Ligand Superfamily Member 13 blood MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
