Paramasivan Naveen Kumar, Masoud Majed, Karsten Carley, Zahid Anza, Kherbek Haidara, Zekeridou Anastasia, Sista Sri Raghav, Dasari Surendra, Knight Andrew M, Mangioris Georgios, Mills John R, McKeon Andrew, Pittock Sean J, Dubey Divyanshu
Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Ann Clin Transl Neurol. 2025 Feb;12(2):280-290. doi: 10.1002/acn3.52254. Epub 2024 Nov 18.
To describe the phenotypes, oncological associations, biomarker profiles, and outcomes across different age groups in patients with ANNA1 (anti-Hu) autoimmunity.
A retrospective review of patients with ANNA1-IgG in serum/CSF between January 1, 2001, and December 31,2019 was performed. Patients were classified into three groups based on the age of symptom onset. Phage immunoprecipitation sequencing (PhIP-Seq) and neurofilament light chain (NfL) measurements were done in patient sera/CSF with archived samples.
Of 122 patients, 81 (66%), 20 (16%), and 21 (17%) patients belonged to older adults, young adults, and pediatric groups, respectively. Lung cancer and neuromuscular presentations were more common in older adults (p < 0.001), while limbic encephalitis and neuroblastoma were more common in pediatric patients (p < 0.005). Most young adults (75%) did not have cancer identified. Proportions of patients with a favorable response to immunotherapy were 20%, 30%, and 52% among older adults, young adults, and pediatric groups, respectively. PhIP-Seq demonstrated significant enrichment for ELAVL4 peptides especially for amino acids 240-289, in the majority of samples evaluated (36/67, 54%). ZIC and SOX2 peptides were significantly enriched in those with central nervous system presentations. Serum NfL levels were elevated in patients with cancer and those with poor long-term outcomes.
Young adults with ANNA1 autoimmunity phenotypically resembled older adults but rarely had an underlying cancer. Pediatric patients frequently presented with limbic encephalitis and neuroblastoma and often responded favorably to immunotherapy. Distinct antigenic signatures may underlie differences in clinical presentations. Serum NfL levels may be a biomarker of poor long-term outcomes in ANNA1 autoimmunity.
描述抗神经元细胞核抗体1（ANNA1，抗Hu）自身免疫患者不同年龄组的表型、肿瘤学关联、生物标志物谱及预后。
对2001年1月1日至2019年12月31日期间血清/脑脊液中存在ANNA1-IgG的患者进行回顾性研究。根据症状出现年龄将患者分为三组。对有存档样本的患者血清/脑脊液进行噬菌体免疫沉淀测序（PhIP-Seq）和神经丝轻链（NfL）检测。
122例患者中，81例（66%）、20例（16%）和21例（17%）患者分别属于老年人、年轻人和儿童组。肺癌和神经肌肉表现在老年人中更常见（p＜0.001），而边缘叶脑炎和神经母细胞瘤在儿童患者中更常见（p＜0.005）。大多数年轻人（75%）未发现患有癌症。免疫治疗反应良好的患者比例在老年人、年轻人和儿童组中分别为20%、30%和52%。在大多数评估样本（36/67，54%）中，PhIP-Seq显示ELAVL4肽尤其是240-289位氨基酸有显著富集。ZIC和SOX2肽在有中枢神经系统表现的患者中显著富集。癌症患者和长期预后较差的患者血清NfL水平升高。
患有ANNA1自身免疫的年轻人在表型上与老年人相似，但很少有潜在癌症。儿童患者常表现为边缘叶脑炎和神经母细胞瘤，且对免疫治疗反应通常良好。不同抗原特征可能是临床表现差异的基础。血清NfL水平可能是ANNA1自身免疫长期预后不良的生物标志物。
