Department of Neurology, University of Cologne, Köln, Germany.
Department of Neurology, St. Katharinen Hospital, Frechen, Germany.
J Neurol Neurosurg Psychiatry. 2017 Sep;88(9):756-760. doi: 10.1136/jnnp-2017-315878. Epub 2017 May 26.
To identify the most relevant antigens for monoclonal antibodies in lymphocytic infiltrates in non-systemic vasculitic neuropathy (NSVN).
Current immunosuppressive treatment for NSVN is insufficient. Monoclonal antibodies might be a treatment option, but the expression profile for targetable antigens on lymphocytic infiltrates in NSVN is unknown.
Sural nerve biopsies from a cohort of patients with NSVN were immunohistochemically studied for the expression of potential candidate antigens in perivascular and intramural lymphocytic infiltrates and correlated with neurological and electrophysiological parameters. 20 patients with treatment naïve NSVN and 5 patients with idiopathic axonal neuropathy were included.
The CD52, BAFF and CD49d antigens were expressed in epineurial, perivascular or intramural lymphocytes of all (20/20) patients. CD52 was most prominently expressed in 21.49% of all inflammatory infiltrates. BAFF and CD49d were detected in 11.25% and 10.99% of these lymphocytes, respectively. The CD20, CD25 and CD126 antigens were found less frequently and at low levels only (CD20: 10/20 patients, 5.84% of lymphocytes; CD25: 17/20 patients, 5.22% of lymphocytes; CD126: 3/20 patients, 0.15% of lymphocytes).
This is the first study in NSVN that identifies antigens expressed by pathogenic lymphocytes, which are potential targets for future monoclonal antibody treatment. Our data suggest that NSVN is amenable to monoclonal antibodies and, moreover, that targeting CD52 may be particularly promising. Our results strongly warrant future clinical trials in NSVN with monoclonal antibodies.
鉴定非系统性血管炎性神经病（NSVN）淋巴细胞浸润中单克隆抗体的最相关抗原。
目前针对 NSVN 的免疫抑制治疗效果不足。单克隆抗体可能是一种治疗选择，但针对 NSVN 淋巴细胞浸润中可靶向抗原的表达谱尚不清楚。
对一组 NSVN 患者的腓肠神经活检进行免疫组织化学研究，以检测血管周围和血管内淋巴细胞浸润中潜在候选抗原的表达，并与神经和电生理参数相关联。共纳入 20 例未经治疗的 NSVN 患者和 5 例特发性轴索神经病患者。
CD52、BAFF 和 CD49d 抗原在所有（20/20）患者的神经外膜、血管周围或血管内淋巴细胞中表达。CD52 在所有炎症浸润中的表达最为显著，占 21.49%。BAFF 和 CD49d 分别在 11.25%和 10.99%的这些淋巴细胞中被检测到。CD20、CD25 和 CD126 抗原的表达频率较低且水平较低（CD20：20 例患者中的 10 例，占淋巴细胞的 5.84%；CD25：20 例患者中的 17 例，占淋巴细胞的 5.22%；CD126：20 例患者中的 3 例，占淋巴细胞的 0.15%）。
这是首次在 NSVN 中鉴定出致病性淋巴细胞表达的抗原，这些抗原可能是未来单克隆抗体治疗的潜在靶点。我们的数据表明，NSVN 适合接受单克隆抗体治疗，而且靶向 CD52 可能特别有前途。我们的结果强烈支持未来在 NSVN 中进行单克隆抗体的临床试验。
