Pathogenic role of newly identified regulatory molecule in autoimmune arthritis

1)TIARP-/-小鼠出现自发性关节炎，血清IL-6水平升高，脾CD11b+细胞计数增加，巨噬细胞IL-6表达增强。TIARP-/-巨噬细胞持续降解IkBA并伴有细胞凋亡失调，表现为IL-6诱导的STAT3磷酸化增加。提示TIARP通过抑制IL-6的产生而在关节炎中发挥负性调节作用，其信号转导途径和TNFa诱导的NF-kB信号转导途径可促进巨噬细胞的凋亡。2)构建了9个环瓜氨酸化GPI多肽(CCG-1-9)。样本来自RA患者(n=208)、健康人(n=174)和其他自身免疫性疾病(n=202)。抗CCG-2、抗CCG-4、抗CCG-7抗体在RA患者中的阳性率约为30.0%，且对RA具有很强的特异性(特异性为99%)。抗CCG-2、抗CCG-4、抗CCG-7抗体与抗CCP、CEP-1和存在HLADRB1 SE等位基因相关。经肿瘤坏死因子拮抗剂治疗后，血清抗CCG-2、7水平显著降低，提示可能是RA的诊断和活动标志物。

1)TIARP-/-mice developed spontaneous arthritis, had high serum levels of IL-6, increased CD11b+ cell count in the spleen, and showed enhanced TNF-induced IL-6 expression in macrophages. Sustained degradation of IkBa with dysregulated apoptosis was also noted in TIARP-/-macrophages, and they showed increased IL-6-induced STAT3 phosphorylation. These findings suggested that TIARP is a negative regulator in arthritis by suppressing IL-6 production, its signaling and TNFa-induced NF-kB signaling result in enhanced apoptosis in macrophages. 2)Nine cyclic citrullinated GPI peptides (CCG-1-9) were constructed. Samples were obtained from patients with RA (n=208), healthy subjects (n=174) and other autoimmune diseases (n=202). Anti-CCG-2, 4, 7 Abs were detected in about 30.0% patients with RA, and these Abs were very specific of RA (specificity 99%). Anti-CCG-2, 4, 7 Abs were correlated with anti-CCP, CEP-1 and the presence of HLA-DRB1 SE allele. Treatment with TNF antagonists significantly reduced the levels of anti-CCG-2, 7, suggesting possible diagnostic and activity marker of RA.