Expression of BAFF receptors in muscle tissue of myositis patients with anti-Jo-1 or anti-Ro52/anti-Ro60 autoantibodies

• Published in: Arthritis research & therapy Vol. 16; no. 5; p. 454
• Main Authors: Kryštůfková, Olga, Barbasso Helmers, Sevim, Venalis, Paulius, Malmström, Vivianne, Lindroos, Eva, Vencovský, Jiří, Lundberg, Ingrid E
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 01.01.2014; BioMed Central
• Subjects: Adult; Aged; Antibodies, Antinuclear - immunology; Antigens, CD19 - metabolism; Autoantibodies - immunology; B-Cell Activating Factor - biosynthesis; B-Cell Activation Factor Receptor - biosynthesis; B-Cell Maturation Antigen - biosynthesis; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; Biopsy; Computer industry; Female; Health aspects; Humans; Immunohistochemistry; Interferon Type I - pharmacology; Male; Medicin och hälsovetenskap; Microscopy, Confocal; Middle Aged; Muscles - metabolism; Muscles - pathology; Myositis - immunology; Myositis - metabolism; Myositis - pathology; Physiological aspects; Ribonucleoproteins - immunology; Syndecan-1 - metabolism; Transmembrane Activator and CAML Interactor Protein - biosynthesis; United States
• ISSN: 1478-6354; 1478-6362; 1478-6362; 1478-6354
• DOI: 10.1186/s13075-014-0454-8

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. 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). 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). 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.