Dipartimento di Medicina di Laboratorio, Fondazione Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy.
Istituto di Patologia Generale, Fondazione Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy.
J Immunol Res. 2018 Mar 25;2018:9646209. doi: 10.1155/2018/9646209. eCollection 2018.
Serological levels of free immunoglobulin light chains (FLCs), produced in excess of heavy chains during synthesis of immunoglobulins by plasma cells, can be considered a direct marker of B cell activity in different systemic inflammatory-autoimmune conditions and may represent a useful predictor of rituximab (RTX) therapeutic efficacy, as reported for rheumatoid arthritis and systemic lupus erythematosus. Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction with antibodies (abs) targeting the acetylcholine receptor (AChR) or the muscle-specific tyrosine kinase (MuSK), inducing muscle weakness and excessive fatigability. As MG course may be remarkably variable, we evaluated the possible use of FLCs as biomarkers of disease activity.
We assessed FLC levels in 34 sera from 17 AChR-MG and from 13 MuSK-MG patients, in comparison with 20 sera from patients with systemic autoimmune rheumatic diseases and 18 from healthy blood donors, along with titers of specific auto-abs and IgG subclass distribution.
We found a statistically significant increase in free chains in both AChR- and MuSK-MG patients, while free chain levels were increased only in AChR-MG. We also observed a significant reduction of both free and chains in 1/4 MuSK-MG patients along with specific abs titer, two months after RTX treatment.
From our data, FLCs appear to be a sensitive marker of B cell activation in MG. Further investigations are necessary to exploit their potential as reliable biomarkers of disease activity.
在浆细胞合成免疫球蛋白时，过量产生的游离免疫球蛋白轻链（FLC）的血清水平可以被视为不同系统性炎症-自身免疫性疾病中 B 细胞活性的直接标志物，并且可能代表利妥昔单抗（RTX）治疗效果的有用预测因子，如类风湿关节炎和系统性红斑狼疮的报道。重症肌无力（MG）是一种神经肌肉接头的自身免疫性疾病，其抗体（abs）针对乙酰胆碱受体（AChR）或肌肉特异性酪氨酸激酶（MuSK），导致肌肉无力和过度疲劳。由于 MG 的病程可能变化很大，我们评估了 FLC 作为疾病活动生物标志物的可能性。
我们评估了 17 例 AChR-MG 和 13 例 MuSK-MG 患者的 34 份血清中的 FLC 水平，与 20 份系统性自身免疫性风湿病患者和 18 份健康献血者的血清进行比较，同时还评估了特定自身抗体和 IgG 亚类分布的滴度。
我们发现 AChR-MG 和 MuSK-MG 患者的游离 链均显著增加，而游离 链水平仅在 AChR-MG 中增加。我们还观察到 1/4 MuSK-MG 患者在接受 RTX 治疗两个月后，其游离 链和 链的水平以及特定 abs 滴度均显著降低。
从我们的数据来看，FLC 似乎是 MG 中 B 细胞激活的敏感标志物。需要进一步研究以利用其作为疾病活动可靠生物标志物的潜力。
