Intrathecal immunoglobulin M (IgM) synthesis has been demonstrated in the early disease stages of multiple sclerosis (MS) as a predictor factor of a worsening disease course. Similarly, increased cerebrospinal fluid (CSF) molecules related to B-cell intrathecal activity have been associated with a more severe MS progression. However, whether CSF levels of IgM are linked to specific inflammatory and clinical profile in MS patients at the time of diagnosis remains to be elucidated.

Using customized Bio-Plex assay, the protein levels of IgG, IgA, IgM, and of 34 other inflammatory molecules, related to B-cell, T-cell, and monocyte/macrophage activity, were analyzed in the CSF of 103 newly diagnosed relapsing–remitting MS patients and 36 patients with other neurological disorders. CSF IgM levels were also correlated with clinical and neuroradiological measures [advanced 3-T magnetic resonance imaging (MRI) parameters], at diagnosis and after 2 years of follow-up.

A 45.6% increase in CSF IgM levels was found in MS patients compared to controls (p = 0.013). CSF IgM levels correlated with higher CSF levels of CXCL13 (p = 0.039), CCL21 (p = 0.023), interleukin 10 (IL-10) (p = 0.025), IL-12p70 (p = 0.020), CX3CL1 (p = 0.036), and CHI3L1 (p = 0.048) and were associated with earlier age of patients at diagnosis (p = 0.008), white matter lesion (WML) number (p = 0.039) and disease activity (p = 0.033) after 2 years of follow-up.

IgMs are the immunoglobulins mostly expressed in the CSF of naive MS patients compared to other neurological conditions at the time of diagnosis. The association between increased CSF IgM levels and molecules related to both B-cell immunity (IL-10) and recruitment (CXCL13 and CCL21) and to macrophage/microglia activity (IL-12p70, CX3CL1, and CHI3L1) suggests possible correlation between humoral and innate intrathecal immunity in early disease stage. Furthermore, the association of IgM levels with WMLs and MS clinical and MRI activity after 2 years supports the idea of key role of IgM in the disease course.

鞘内免疫球蛋白 M (IgM) 合成已在多发性硬化症 (MS) 的早期疾病阶段被证明是疾病恶化的预测因素。同样，与 B 细胞鞘内活动相关的脑脊液 (CSF) 分子增加与更严重的 MS 进展有关。然而，脑脊液 IgM 水平是否与诊断时 MS 患者的特定炎症和临床特征相关仍有待阐明。

使用定制的 Bio-Plex 测定法，在 103 例新诊断的复发患者的 CSF 中分析了与 B 细胞、T 细胞和单核细胞/巨噬细胞活性相关的 IgG、IgA、IgM 和其他 34 种炎症分子的蛋白质水平– 缓解 MS 患者和 36 名患有其他神经系统疾病的患者。CSF IgM 水平也与临床和神经放射学测量[高级 3-T 磁共振成像 (MRI) 参数]、诊断时和 2 年随访后相关。

与对照组相比，MS 患者的 CSF IgM 水平增加了 45.6%（p= 0.013)。CSF IgM 水平与 CSF 中较高的 CXCL13 水平相关（p= 0.039), CCL21 (p= 0.023)、白细胞介素 10 (IL-10) (p= 0.025), IL-12p70 (p= 0.020），CX3CL1（p= 0.036) 和 CHI3L1 (p= 0.048) 并且与诊断时患者的早期年龄相关 (p= 0.008), 白质病变 (WML) 数 (p= 0.039) 和疾病活动 (p= 0.033）经过 2 年的随访。

与诊断时的其他神经系统疾病相比，IgM 是主要在初始 MS 患者的 CSF 中表达的免疫球蛋白。CSF IgM 水平升高与 B 细胞免疫 (IL-10) 和募集相关分子 (CXCL13 和 CCL21) 以及巨噬细胞/小胶质细胞活性 (IL-12p70、CX3CL1 和 CHI3L1) 之间的关联表明体液和疾病早期的先天性鞘内免疫。此外，2 年后 IgM 水平与 WML 和 MS 临床和 MRI 活动的关联支持了 IgM 在疾病过程中的关键作用的观点。