Kollewe Katja, Wurster Ulrich, Sinzenich Thomas, Körner Sonja, Dengler Reinhard, Mohammadi Bahram, Petri Susanne
Department of Neurology, Medical School Hannover, Hannover, Germany.
Department of Neurology, University of Lübeck, Lübeck, Germany; CNS-LAB, International Neuroscience Institute, Hannover, Germany.
PLoS One. 2015 Apr 14;10(4):e0125339. doi: 10.1371/journal.pone.0125339. eCollection 2015.
Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder with typical onset in the 5th- 6th decade of life. The hypothesis of an autoimmune origin of ALS receives less attention today, but immunological phenomena still seem to be involved and mechanisms such as protective autoimmunity may be important. Detection of antibodies against a variety of gangliosides has been repeatedly described in ALS-patients by several authors, but widely differing frequencies and titres have been reported. Therefore, we investigated the presence of six common antibodies with a commercially available test panel for GA1, GM1, GM2, GD1a, GD1b and GQ1b in a large group of clinically well-characterized ALS patients and compared them to a collective of 200 healthy blood donors.
IgG and IgM antibodies to the six gangliosides asialoGM1 (GA1), GM1, GM2, GD1a, GD1b, GQ1b were determined by GanglioCombi ELISA in sera of 84 ALS patients. Results were expressed as a %-ratio of a highly positive control and categorized as negative (<30%), borderline (30-50%), moderately (50-100%) and strongly positive (>100%). The values obtained from 200 Swiss blood donors served as a reference group.
In twenty-two (26.2%) ALS-patients elevated anti-ganglioside antibodies could be detected: Taking all subspecific antibodies together, IgG antibodies were found in 9/84 (10.7%) and IgM in 15/84 (17.9%) patients. There was no correlation between age, gender, site of onset or survival and anti-ganglioside-positive/-negative titres in ALS-patients. No statistically significant difference in the frequency of anti-ganglioside antibodies compared to the group of healthy blood donors was found.
Even with this more comprehensive approach, anti-ganglioside antibody frequencies and patterns in our ALS cohort closely resembled the values measured in healthy controls. In accordance with other studies, we did not observe any association of a distinct ALS phenotype with elevated anti-ganglioside antibodies or an impact on survival.
肌萎缩侧索硬化症（ALS）是一种毁灭性的神经退行性疾病，典型发病年龄在50至60岁之间。如今，ALS自身免疫起源的假说受到的关注较少，但免疫现象似乎仍与之相关，诸如保护性自身免疫等机制可能很重要。多位作者反复报道在ALS患者中检测到针对多种神经节苷脂的抗体，但报道的频率和滴度差异很大。因此，我们使用市售检测试剂盒，检测了一大群临床特征明确的ALS患者体内针对GA1、GM1、GM2、GD1a、GD1b和GQ1b这六种常见抗体的情况，并将其与200名健康献血者群体进行了比较。
采用神经节苷脂组合酶联免疫吸附测定法（GanglioCombi ELISA），检测84例ALS患者血清中针对六种神经节苷脂脱唾液酸GM1（GA1）、GM1、GM2、GD1a、GD1b、GQ1b的IgG和IgM抗体。结果以高阳性对照的百分比表示，并分为阴性（<30%）、临界（30 - 50%）、中度（50 - 100%）和强阳性（>100%）。从200名瑞士献血者获得的值作为参考组。
在22例（26.2%）ALS患者中可检测到抗神经节苷脂抗体升高：将所有亚特异性抗体合计，9/84例（10.7%）患者检测到IgG抗体，15/84例（17.9%）患者检测到IgM抗体。ALS患者的年龄、性别、发病部位或生存期与抗神经节苷脂抗体阳性/阴性滴度之间无相关性。与健康献血者组相比，未发现抗神经节苷脂抗体频率有统计学显著差异。
即便采用这种更全面的方法，我们ALS队列中的抗神经节苷脂抗体频率和模式仍与健康对照中测得的值非常相似。与其他研究一致，我们未观察到特定ALS表型与抗神经节苷脂抗体升高之间存在关联，也未观察到其对生存期有影响。
