摘要：背景：係統性紅斑狼瘡(SLE)是一種有著顯著異質性的自身免疫性疾病。盡管我們付出了巨大的努力，但我們對重症SLE的血清蛋白表型的了解仍然有限。此研究旨在探討SLE的血清蛋白模式，尤其是伴有不可逆的髒器損害的狼瘡以及活動性狼瘡腎炎。方法：我們使用延長免疫分析法(PEA)評估SLE患者(n = 75)和年齡匹配的健康對照受試者(n = 23)中92種炎症相關蛋白的血清水平。基於器官損傷(有/無，42/33)和活檢證實的LN(有/無，27/48;活動LN，n = 13;無活性LN，n = 14)進行亞組分析。結果：在SLE和健康對照之間的30個失調蛋白(P corr<0.05)中，SLE中上調的蛋白是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尚未見於SLE報道。在器官損傷患者中檢測到IL8、CCL2 / MCP1、CCL11和MMP10水平升高(P corr<0.05)，其中CCL11和MMP10的血清水平在器官損傷預測中特別有用。對於LN的患者，活動性LN中檢測到升高的CSF1、sIL15RA、sCD40、sCX3CL1、蛋白酶8、sIL18R1、bNGF和GDNF水平(P corr<0.05)。除GDNF外，所有LN相關標誌物均可用於預測活動性腎髒疾病。結論：這種高度敏感的PEA分析方法鑒定了SLE的血清模式，包括器官損傷、活動性狼瘡腎炎等情況下血清蛋白表型的特點，並檢測到許多新的候選蛋白質。它們在SLE中作為生物標記物的確切角色和適宜性值得進一步研究。

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