Increased serum IL-2, IL-4, IL-5 and IL-12p70 levels in AChR subtype generalized myasthenia gravis.

Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions. Cytokines play important roles in facilitating the immune response and augmenting the pathogenic antibody production. The current study aims to sensitively characterize the serum levels of cytokines with very low concentration in generalized MG (gMG). Using ultrasensitive single-molecule arrays (SIMOA), we measured serum IL-2, IL-4, IL-5 and IL-12p70 in 228 participants including 152 immunotherapy-naïve anti-acetylcholine receptor (AChR) subtype gMG from Huashan MG registry and 76 age-matched healthy controls. Subgroup analysis was then performed by stratifying patients according to the onset ages, MGFA classification, disease duration at baseline. Serum IL-2, IL-4, IL-5 and IL-12p70 levels were significantly elevated in gMG compared to controls (0.179 pg/mL versus 0.011 pg/mL, P < 0.0001; 0.029 pg/mL versus 0.018 pg/mL, P = 0.0259; 0.215 pg/mL versus 0.143 pg/mL, P = 0.0007; 0.132 pg/mL versus 0.118 pg/mL, P = 0.0401). Subgroup analysis revealed that IL-2 levels were slightly elevated in gMG with MGFA II compared to MGFA III/IV (0.195 pg/mL versus 0.160 pg/mL, P = 0.022), as well as elevated levels of IL-2 (0.220 pg/mL versus 0.159 pg/mL, P = 0.0002) and IL-5 (0.251 pg/mL versus 0.181 pg/mL, P = 0.004) in late-onset gMG compared with the early-onset gMG. gMG patients with a long duration had a significant increased serum IL-12p70 than those with a short duration (0.163 pg/mL versus 0.120 pg/mL, P = 0.011). Serum IL-2, IL-4, IL-5 and IL-12p70 levels were increased in AChR subtype gMG using ultrasensitive measurement. Serum cytokines with very low concentrations may provide as potential biomarkers in stratifying gMG patients in future prospective cohort studies.

重症肌无力（MG）是一种影响神经肌肉接头的自身免疫性疾病。细胞因子在促进免疫反应和增加致病性抗体产生方面发挥重要作用。本研究旨在灵敏地描述全身型重症肌无力（gMG）中浓度极低的细胞因子的血清水平。 我们使用超灵敏单分子阵列（SIMOA）技术，对228名参与者的血清白细胞介素 - 2（IL - 2）、白细胞介素 - 4（IL - 4）、白细胞介素 - 5（IL - 5）和白细胞介素 - 12p70进行了检测，其中包括来自华山重症肌无力登记处的152名未接受免疫治疗的抗乙酰胆碱受体（AChR）亚型全身型重症肌无力患者以及76名年龄匹配的健康对照者。然后根据发病年龄、美国重症肌无力基金会（MGFA）分级以及基线时的病程对患者进行分层，进行亚组分析。 与对照组相比，全身型重症肌无力患者血清中IL - 2、IL - 4、IL - 5和IL - 12p70水平显著升高（分别为0.179皮克/毫升对0.011皮克/毫升，P < 0.0001；0.029皮克/毫升对0.018皮克/毫升，P = 0.0259；0.215皮克/毫升对0.143皮克/毫升，P = 0.0007；0.132皮克/毫升对0.118皮克/毫升，P = 0.0401）。亚组分析显示，与MGFA III/IV级相比，MGFA II级的全身型重症肌无力患者IL - 2水平略高（0.195皮克/毫升对0.160皮克/毫升，P = 0.022），并且与早发型全身型重症肌无力相比，晚发型全身型重症肌无力患者的IL - 2（0.220皮克/毫升对0.159皮克/毫升，P = 0.0002）和IL - 5（0.251皮克/毫升对0.181皮克/毫升，P = 0.004）水平升高。病程较长的全身型重症肌无力患者血清IL - 12p70水平明显高于病程较短的患者（0.163皮克/毫升对0.120皮克/毫升，P = 0.011）。 通过超灵敏检测发现，AChR亚型全身型重症肌无力患者血清中IL - 2、IL - 4、IL - 5和IL - 12p70水平升高。极低浓度的血清细胞因子可能在未来的前瞻性队列研究中作为对全身型重症肌无力患者进行分层的潜在生物标志物。