关键词： APS, primary antiphospholipid syndrome AUC, area under the curve Ab, autoantibody Autoantibodies Autoimmune diseases CCP, cyclic citrulinated peptide CXCL10, C-X-C motif chemokine 10 F, female FLC, free light chains Free light chains HC, healthy controls IFN, interferon Interferon signature M, male MCTD, mixed connective tissue disease MDA, malondialdehyde NK, natural killer PC, phosphorylcholine RA, rheumatoid arthritis RF, rheumatoid factor RNP, ribonucleoprotein ROC, Receiver Operating Characteristics SAD, systemic autoimmune diseases SD, standard deviation SLE, systemic lupus erythematosus Scl, systemic sclerosis SjS, Sjögren's syndrome TH1, T helper type 1 TNF-R1, tumor necrosis factor receptor 1 UCTD, undetermined connective tissue disease VAS, visual analogical scale κ, kappa λ, lambda

来  源：   DOI：10.1016/j.jtauto.2021.100090   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
High amount of polyclonal free light chains (FLC) are reported in systemic autoimmune diseases (SAD) and we took advantage of the PRECISESADS study to better characterize them. Serum FLC levels were explored in 1979 patients with SAD (RA, SLE, SjS, Scl, APS, UCTD, MCTD) and 614 healthy controls. Information regarding clinical parameters, disease activity, medications, autoantibodies (Ab) and the interferon α and/or γ scores were recorded. Among SAD patients, 28.4% had raised total FLC (from 12% in RA to 30% in SLE and APS) with a normal kappa/lambda ratio. Total FLC levels were significantly higher in SAD with inflammation, active disease in SLE and SjS, and an impaired pulmonary functional capacity in SSc, while independent from kidney impairment, infection, cancer and treatment. Total FLC concentrations were positively correlated among the 10/17 (58.8%) autoantibodies (Ab) tested with anti-RNA binding protein Ab (SSB, SSA-52/60 kDa, Sm, U1-RNP), anti-dsDNA/nucleosome Ab, rheumatoid factor and negatively correlated with complement fractions C3/C4. Finally, examination of interferon (IFN) expression as a potential driver of FLC overexpression was tested showing an elevated level of total FLC among patients with a high IFNα and IFNγ Kirou\'s score, a strong IFN modular score, and the detection in the sera of B-cell IFN dependent factors, such as TNF-R1/TNFRSF1A and CXCL10/IP10. In conclusion, an elevated level of FLC, in association with a strong IFN signature, defines a subgroup of SAD patients, including those without renal affectation, characterized by increased disease activity, autoreactivity, and complement reduction.
摘要：
在系统性自身免疫性疾病（SAD）中报道了大量的多克隆游离轻链（FLC），我们利用PRECISESADS研究来更好地表征它们。在1979年SAD患者中探讨了血清FLC水平（RA，SLE,SjS,Scl,APS,UCTD,MCTD）和614名健康对照。有关临床参数的信息，疾病活动,药物,记录自身抗体（Ab）和干扰素α和/或γ评分。在SAD患者中，28.4％的人提高了总FLC（从RA的12％提高到SLE和APS的30％），κ/λ比率正常。总FLC水平显著高于SAD伴炎症，SLE和SjS的活动性疾病，SSc的肺功能受损，虽然独立于肾脏损害，感染,癌症和治疗。总FLC浓度在10/17(58.8%)自身抗体(Ab)与抗RNA结合蛋白Ab(SSB,SSA-52/60kDa,Sm,U1-RNP),抗dsDNA/核小体Ab，类风湿因子与补体组分C3/C4呈负相关。最后,作为FLC过表达的潜在驱动因素的干扰素（IFN）表达的检查进行了测试，显示在IFNα和IFNγKirou评分较高的患者中总FLC水平升高，强大的IFN模块评分，以及血清中B细胞IFN依赖因子的检测，如TNF-R1/TNFRSF1A和CXCL10/IP10。总之,FLC水平升高，与强大的IFN签名相关联，定义了一个SAD患者亚组，包括那些没有肾脏影响的人，以疾病活动增加为特征，自反应性,补充减少。
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