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.

重症肌无力（MG）是一种自身抗体介导的神经肌肉疾病，其临床病程不可预测。血清游离轻链 (FLC) 已成为 MG 的一种有前途的生物标志物，但它们在 MG 不同亚型以及预测疾病进展中的作用仍然未知。

我们在胸腺切除术后随访期间研究了 58 名全身性 MG 患者的血浆，以确定 κ 和 λ FLC 以及 κ/λ 比值。在 30 名患者的亚队列中，我们使用 Olink 检查了 92 种与免疫肿瘤学相关的蛋白质的表达。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 MG (LOMG) 患者的平均 κ/λ 比值显着高于早发 MG 患者 ( P  = 0.004)。与健康对照相比，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) 和精氨酸酶 1 (ARG1) 在 MG 患者中的表达存在差异。临床结果与 FLC 或检测的蛋白质之间没有显着关联。

总之，κ/λ 比值升高表明 LOMG 中存在长期异常的克隆浆细胞功能。免疫肿瘤学相关的蛋白质组学分析显示免疫调节途径的改变。我们的研究结果将 FLC 比率确定为 LOMG 的生物标志物，并呼吁进一步研究 MG 的免疫调节途径。