背景:为了调查Ranvier在各种周围神经病变种中的自身抗体患病率和同种型,比较血清阴性和血清阳性患者的临床特征,并阐明抗体产生的潜在免疫机制。
方法:抗抗神经成束蛋白-155(NF155)的抗体,NF186,contactin-1(CNTN1),CNTN2,接触蛋白相关蛋白1(CASPR1),和CASPR2通过基于细胞的测定鉴定。使用多重荧光免疫分析法分析抗NF155抗体阳性慢性炎症性脱髓鞘性多发性神经病(NF155+CIDP)和Ranvier抗体阴性CIDP(Ab-CIDP)患者的血浆细胞因子,在细胞培养模型中进行了体外验证。
结果:在368个血浆样本中,在45个人中发现了50例Ranvier自身抗体,主要是CIDP病例(69例患者中的25例)和122例格林-巴利综合征患者中的10例。抗-NF155和CNTN1-IgG是唯一的ClDP。十四个样本是NF155-IgG,主要是IgG4亚类,与CI相关的DP特征,包括早期发作,震颤,感觉障碍,脑脊液蛋白升高,延长的运动潜伏期,传导阻滞,治疗反应差。NF155-IgG对CIDP的敏感性较低(20.28%),但特异性较高(100%),随着震颤和运动潜伏期延长,上升到88.88%。NF155+CIDP中的细胞因子分析揭示了涉及辅助性T细胞的不同免疫反应,toll样受体途径。一些NF155+CIDP患者循环NF155特异性B细胞产生NF155-IgG,而不存在抗原,提示治疗潜力。
结论:该研究强调了NF155-IgG对诊断具有独特特征的CIDP的高度特异性和敏感性。对循环NF155特异性B细胞表型的进一步研究可能为B细胞定向治疗铺平道路。
BACKGROUND: To investigate Ranvier\'s autoantibodies prevalence and isotypes in various peripheral neuropathy variants, compare clinical features between seronegative and seropositive patients, and elucidate immune mechanisms underlying antibody generation.
METHODS: Antibodies against anti-neurofascin-155 (NF155), NF186, contactin-1 (CNTN1), CNTN2, contactin-associated protein 1 (CASPR1), and CASPR2 were identified through cell-based assays. Plasma cytokines were analyzed in anti-NF155 antibody-positive chronic inflammatory demyelinating polyneuropathy (NF155+ CIDP) and Ranvier\'s antibodies-negative CIDP (Ab- CIDP) patients using a multiplexed fluorescent immunoassay, validated in vitro in a cell culture model.
RESULTS: In 368 plasma samples, 50 Ranvier\'s autoantibodies were found in 45 individuals, primarily in CIDP cases (25 out of 69 patients) and in 10 out of 122 Guillain-Barré syndrome patients. Anti-NF155 and CNTN1-IgG were exclusive to CIDP. Fourteen samples were NF155-IgG, primarily IgG4 subclass, linked to CIDP features including early onset, tremor, sensory disturbance, elevated CSF protein, prolonged motor latency, conduction block, and poor treatment response. NF155-IgG had low sensitivity (20.28%) but high specificity (100%) for CIDP, rising to 88.88% with tremor and prolonged motor latency. Cytokine profiling in NF155+ CIDP revealed distinct immune responses involving helper T cells, toll-like receptor pathways. Some NF155+ CIDP patients had circulating NF155-specific B cells producing NF155-IgG without antigen presence, suggesting therapeutic potential.
CONCLUSIONS: The study emphasizes the high specificity and sensitivity of NF155-IgG for diagnosing CIDP characterized by distinctive features. Further investigation into circulating NF155-specific B cell phenotypes may pave the way for B cell directed therapy.