Kryštůfková Olga, Barbasso Helmers Sevim, Venalis Paulius, Malmström Vivianne, Lindroos Eva, Vencovský Jiří, Lundberg Ingrid E
Arthritis Res Ther. 2014 Oct 10;16(5):454. 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.
抗Jo-1和抗Ro52自身抗体在肌炎患者中很常见，但其产生机制尚不清楚。产生自身抗体的细胞的存活依赖于肿瘤坏死因子家族的B细胞激活因子（BAFF）。抗Jo-1阳性肌炎患者血清中的BAFF水平升高，并受I型干扰素（IFN）影响。肌炎肌肉中存在产生IFN的细胞和BAFF mRNA表达。我们研究了肌肉组织中BAFF受体的表达与抗Jo-1和抗Ro52/抗Ro60自身抗体以及I型IFN标志物的关系。
对根据自身抗体谱选择的23例肌炎患者和7例健康对照的肌肉活检组织进行BAFF受体（BAFF-R）、B细胞成熟抗原（BCMA）和跨膜激活剂、钙调蛋白和亲环素配体相互作用分子（TACI）表达的研究。对19个样本进行血浆（CD138）和B细胞（CD19）标志物评估。将每单位面积阳性细胞数与浆细胞样树突状细胞（pDC）标志物血液树突状细胞抗原2（BDCA-2）和IFNα/β诱导的抗黏液病毒蛋白1（MX-1）的表达进行比较。
BAFF-R、BCMA和TACI分别在5例、7例和7例患者中表达，与对照组及无这些自身抗体的患者相比，在抗Jo-1阳性和/或抗Ro52/抗Ro60阳性患者中更常见（P值：BAFF-R为0.007，BCMA为0.03，TACI为0.07）。共聚焦显微镜证实受体与B细胞和浆细胞存在局部关联。CD138阳性细胞数与BCMA阳性细胞数相关（r = 0.79；P = 0.001）。BDCA-2的表达与CD138阳性细胞数相关，与BCMA阳性细胞数呈边缘相关（分别为r = 0.54和0.42；P值分别为0.04和0.06）。TACI阳性染色细胞数与MX-1区域之间存在边缘相关性（r = 0.38，P = 0.08）。
肌炎患者肌肉中B细胞和浆细胞上BAFF受体的表达模式表明BAFF在有抗Jo-1或抗Ro52/抗Ro60自身抗体的肌炎患者肌肉组织自身抗体产生中起局部作用。BAFF的产生可能受pDC产生的I型IFN影响。因此，B细胞相关分子途径可能参与了这部分患者肌炎的发病机制。
