摘要：背景：系统性红斑狼疮(SLE)是一种有着显着异质性的自身免疫性疾病。尽管我们付出了巨大的努力，但我们对重症SLE的血清蛋白表型的了解仍然有限。此研究旨在探讨SLE的血清蛋白模式，尤其是伴有不可逆的脏器损害的狼疮以及活动性狼疮肾炎。方法：我们使用延长免疫分析法(PEA)评估SLE患者(n = 75)和年龄匹配的健康对照受试者(n = 23)中92种炎症相关蛋白的血清水平。基于器官损伤(有/无，42/33)和活检证实的LN(有/无，27/48;活动LN，n = 13;无活性LN，n = 14)进行亚组分析。结果：在SLE和健康对照之间的30个失调蛋白(P corr<0.05)中，SLE中上调的蛋白是sirtuin 2、白介素18(IL-18)和蛋白酶酶8(P corr<0.0006)。其中，sirtuin 2和蛋白酶 8尚未见于SLE报道。在器官损伤患者中检测到IL8、CCL2 / MCP1、CCL11和MMP10水平升高(P corr<0.05)，其中CCL11和MMP10的血清水平在器官损伤预测中特别有用。对于LN的患者，活动性LN中检测到升高的CSF1、sIL15RA、sCD40、sCX3CL1、蛋白酶8、sIL18R1、bNGF和GDNF水平(P corr<0.05)。除GDNF外，所有LN相关标志物均可用于预测活动性肾脏疾病。结论：这种高度敏感的PEA分析方法鉴定了SLE的血清模式，包括器官损伤、活动性狼疮肾炎等情况下血清蛋白表型的特点，并检测到许多新的候选蛋白质。它们在SLE中作为生物标记物的确切角色和适宜性值得进一步研究。

        附原文:AbstractBackground Systemic lupus erythematosus (SLE) is a remarkably heterogeneous autoimmune disease. Despite tremendous efforts, our knowledge of serum protein patterns in severe SLE phenotypes is still limited. We investigated the serum protein pattern of SLE, with special emphasis on irreversible organ damage and active lupus nephritis (LN) as assessed by renal Systemic Lupus Erythematosus Disease Activity Index.Methods We used proximity extension immunoassay (PEA, Proseek Multiplex, Olink) to assess the serum levels of ninety-two inflammation-related proteins in Czech patients with SLE (n = 75) and age-matched healthy control subjects (n = 23). Subgroup analysis was carried out on the basis of organ damage (with/without, 42/33) and

        biopsy-proven LN (with/without, 27/48; active LN, n = 13; inactive LN, n = 14).Results Of thirty deregulated proteins between SLE and the healthy controls (P corr < 0.05), the top upregulated proteins in SLE were sirtuin 2, interleukin 18 (IL18), and caspase 8 (P corr < 0.0006). Of these, sirtuin 2 and caspase 8 had not yet been reported with SLE. Elevated levels of IL8, CCL2/MCP1, CCL11, and MMP10 (P corr < 0.05) were detected in patients with organ damage for which the serum levels of CCL11 and MMP10 were particularly informative in organ damage prediction. Comparing patients based on LN, elevated levels of CSF1, sIL15RA, sCD40, sCX3CL1, caspase 8, sIL18R1, bNGF, and GDNF (P corr < 0.05) were detected in active LN. Except GDNF, all LN-associated markers showed usefulness in prediction of active renal disease. Conclusions This highly sensitive PEA analysis identified the serum pattern of SLE, organ damage, and active LN, with many novel candidate proteins detected. Their exact role and suitability as biomarkers in SLE deserve further investigation.

        引自：Anna Petrackova, Andrea SmrzovaSerum protein pattern associated with organ damage and lupus nephritis in systemic lupus erythematosus revealed by PEA immunoassayPetrackova et al. ClinProteom (2017) 14:32 DOI 10.1186/s12014-017-9167-8