Circulating Interferon-Inducible Protein IFI16 Correlates With Clinical and Serological Features in Rheumatoid Arthritis
Circulating Interferon-Inducible Protein IFI16 Correlates With Clinical and Serological Features in Rheumatoid Arthritis
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DOI：
10.1002/acr.22695
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发表时间：
2016-04-01
影响因子：
4.7
通讯作者：
Gerli, Roberto
中科院分区：
文献类型：
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作者：
Alunno, Alessia;Caneparo, Valeria;Gerli, Roberto
目标。干扰素诱导蛋白16 （IFI16）已在自身免疫性/炎症性疾病患者的血清中检测到，但在健康受试者中未检测到。这种泄漏导致对这种自身蛋白的耐受性丧失和自身抗体的产生。本研究探讨IFI16蛋白及抗IFI16抗体在类风湿关节炎（RA）中的临床意义。采用酶联免疫吸附法测定154例RA患者和182例健康对照者血清样本、21例RA患者和25例骨关节炎（OA）患者滑液样本中IFI16蛋白和抗IFI16抗体水平。RA患者血清中IFI16和抗IFI16抗体的平均水平均高于健康对照组，IFI16浓度与抗IFI16抗体滴度直接相关。大多数可检测到循环IFI16蛋白的RA患者类风湿因子(RF)/抗环瓜氨酸肽抗体（anti-CCP）阳性。后一组的抗ifi16抗体也呈阳性。RA患者中IFI16蛋白和抗IFI16抗体的平均SF浓度均高于对照OA患者。有趣的是，循环中存在的IFI16蛋白，而不是抗IFI16抗体，与ra相关的肺部疾病显著相关。这种相关性不依赖于抗ifi16抗体的存在、性别和吸烟习惯。我们的数据表明，RA中高水平的循环IFI16在RF/抗ccp阳性RA患者中更为常见，并且与肺部受累显著相关。循环IFI16蛋白作为RA新的临床生物标志物的相关性有待进一步研究证实。
Objective. The interferon-inducible protein 16 (IFI16) has been detected in sera from patients with autoimmune/inflammatory diseases, but not in healthy subjects. This leaking leads to loss of tolerance toward this self-protein and the development of autoantibodies. In this study, clinical significance of both IFI16 protein and anti-IFI16 antibodies in rheumatoid arthritis (RA) was investigated.Methods. IFI16 protein and anti-IFI16 antibody levels were assessed by enzyme-linked immunosorbent assay in serum samples from 154 RA patients and 182 healthy controls, and in synovial fluid (SF) samples from 21 RA patients and 25 patients with osteoarthritis (OA).Results. Mean serum levels for both IFI16 and anti-IFI16 antibodies were higher in RA patients than in healthy controls, with a direct correlation between IFI16 concentration and anti-IFI16 antibody titer. The majority of RA patients with detectable circulating IFI16 protein were also positive for rheumatoid factor (RF)/anti-cyclic citrullinated peptide antibody (anti-CCP). The latter group was found to be positive for anti-IFI16 antibodies as well. The mean SF concentrations of both IFI16 protein and anti-IFI16 antibodies were higher in RA patients when compared with control OA patients. Interestingly, the presence of circulating IFI16 protein, but not anti-IFI16 antibodies, significantly correlated with RA-associated pulmonary disease. This correlation was not dependent on the presence of anti-IFI16 antibodies, sex, and smoking habit.Conclusion. Our data demonstrate that the high levels of circulating IFI16 in RA are more frequent in RF/anti-CCP-positive RA patients and significantly associated with pulmonary involvement. The relevance of circulating IFI16 protein as a new clinical biomarker of RA should be verified with additional studies.