Abstract：
Myasthenia gravis (MG) is an autoantibody-mediated neuromuscular disease with an unpredictable clinical course. Serum free light chains (FLCs) have risen as a promising biomarker for MG, but their role in different subtypes of MG and in predicting disease progression is still uncharted. We investigated plasma from 58 generalized MG patients during post-thymectomy follow-up to determine κ and λ FLC and κ/λ ratio. In a subcohort of 30 patients, we examined the expression of 92 proteins associated with immuno-oncology using Olink. We further studied the ability of FLCs or proteomic markers to differentiate disease severity. Patients with late-onset MG (LOMG) displayed significantly higher mean κ/λ ratio than patients with early-onset MG (P = 0.004). Inducible T-cell co-stimulator ligand (ICOSLG), matrix metalloproteinase 7 (MMP7), hepatocyte growth factor (HGF), and arginase 1 (ARG1) were differentially expressed in MG patients compared to healthy controls. There were no significant associations between clinical outcomes and FLCs or the assayed proteins. In conclusion, an elevated κ/λ ratio suggests long-lasting aberrant clonal plasma cell function in LOMG. Immuno-oncology-related proteomic analysis showed alterations in immunoregulatory pathways. Our findings pinpoint the FLC ratio as a biomarker for LOMG and call for further investigation of the immunoregulatory pathways in MG.
摘要：
重症肌无力（MG）是一种自身抗体介导的神经肌肉疾病，临床病程不可预测。血清游离轻链（FLC）已成为MG的有希望的生物标志物，但它们在MG不同亚型和预测疾病进展中的作用尚不清楚。我们在胸腺切除术后随访期间调查了58例广义MG患者的血浆，以确定κ和λFLC以及κ/λ比。在30名患者的亚队列中，我们使用Olink检测了与免疫肿瘤学相关的92种蛋白的表达.我们进一步研究了FLC或蛋白质组标记区分疾病严重程度的能力。晚发性MG（LOMG）患者的平均κ/λ比值明显高于早发性MG（P=0.004）。诱导型T细胞共刺激配体（ICOSLG），基质金属蛋白酶7（MMP7），肝细胞生长因子（HGF），与健康对照组相比，精氨酸酶1（ARG1）在MG患者中差异表达。临床结果与FLC或测定的蛋白质之间没有显着关联。总之,κ/λ比值升高提示LOMG存在持久的异常克隆浆细胞功能。免疫肿瘤学相关的蛋白质组分析显示免疫调节途径的改变。我们的发现确定了FLC比率作为LOMG的生物标志物，并呼吁进一步研究MG中的免疫调节途径。
