Ivanova Kristīne, Zolovs Maksims, Blennow Kaj, Zetterberg Henrik, Kurjāne Nataļja, Ķēniņa Viktorija
Department of Doctoral Studies, Rīga Stradinš University, Rīga, Latvia.
Department of Rheumatology, Pauls Stradiņš Clinical University Hospital, Rīga, Latvia.
Front Med (Lausanne). 2024 Aug 2;11:1412706. doi: 10.3389/fmed.2024.1412706. eCollection 2024.
Systemic sclerosis (SSc) is a rare autoimmune disease with multiple organ involvement; however, the contribution of the nervous system (NS) remains relatively understudied. There are no specific data on the role of the autoimmune response and inflammation in the development of peripheral nerve system (PNS) damage in SSc and markers to assess this damage have yet to be identified.
The primary objective of this study was to define the autoimmune mechanisms that lead to neuropathy by identifying antibodies (Abs) that target certain component of the NS or are associated with SSc. The secondary objective was to identify markers of NS damage that correlate with the detection and progression of polyneuropathy (PNP).
This study included patients diagnosed with SSc who met ACR/EULAR 2013 classification criteria at two leading Latvian hospitals between January 2016 and December 2021. Patients underwent a nerve conduction study (NCS). The SSc-associated Abs, Abs against myelin-associated glycoprotein (MAG) and anti-ganglioside Abs (GM1, GM2, GD1a, GD1b and GQ1b) were analysed. Potential serum PNS biomarkers-neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), fibroblast growth factor 21 (FGF21) and growth/differentiation factor 15 (GDF15)-were measured.
We recruited 103 Caucasian patients diagnosed with SSc. SSc-associated Abs did not differ significantly between patients with and without PNP ( > 0.05). Anti-MAG and anti-ganglioside Abs in patients with PNP did not present a significant increase above the reference range. NfL, GFAP and GDF15 were significantly elevated in the presence of PNP ( < 0.05), with a moderate to high effect size ( = 0.36-0.65). Our regression analysis revealed a strong association between the HAQ-DI score, older age, male gender and the risk of developing PNP.
The development of PNP in patients with SSc is most likely due to ageing, natural progression and the sequelae of the disease. Several serum biomarkers-NfL, GFAP and GDF15-could be used as relevant diagnostic biomarkers for PNP in patients with SSc. Future studies are warranted to validate the diagnostic efficacy of these biomarkers and to unravel the complex interplay of factors leading to PNP in patients with SSc.
系统性硬化症（SSc）是一种累及多器官的罕见自身免疫性疾病；然而，神经系统（NS）在其中的作用仍相对研究较少。关于自身免疫反应和炎症在SSc患者外周神经系统（PNS）损伤发展中的作用，目前尚无具体数据，且评估这种损伤的标志物也有待确定。
本研究的主要目的是通过鉴定靶向NS特定成分或与SSc相关的抗体（Abs）来确定导致神经病变的自身免疫机制。次要目的是确定与多发性神经病（PNP）的检测和进展相关的NS损伤标志物。
本研究纳入了2016年1月至2021年12月期间在拉脱维亚两家主要医院被诊断为符合美国风湿病学会/欧洲抗风湿病联盟（ACR/EULAR）2013分类标准的SSc患者。患者接受了神经传导研究（NCS）。分析了与SSc相关的抗体、抗髓鞘相关糖蛋白（MAG）抗体和抗神经节苷脂抗体（GM1、GM2、GD1a、GD1b和GQ1b）。检测了潜在的血清PNS生物标志物——神经丝轻链（NfL）、胶质纤维酸性蛋白（GFAP）、成纤维细胞生长因子21（FGF21）和生长/分化因子15（GDF15）。
我们招募了103例被诊断为SSc的白种人患者。有PNP和无PNP的患者之间，与SSc相关的抗体无显著差异（>0.05）。PNP患者的抗MAG和抗神经节苷脂抗体在参考范围之上未出现显著升高。存在PNP时，NfL、GFAP和GDF15显著升高（<0.05），效应大小为中度至高（=0.36 - 0.65）。我们的回归分析显示，健康评估问卷残疾指数（HAQ - DI）评分、年龄较大、男性性别与发生PNP的风险之间存在强关联。
SSc患者发生PNP很可能是由于衰老、疾病的自然进展和后遗症。几种血清生物标志物——NfL、GFAP和GDF15——可作为SSc患者PNP的相关诊断生物标志物。未来有必要开展研究以验证这些生物标志物的诊断效能，并阐明导致SSc患者发生PNP的复杂因素相互作用。
