自身免疫性/副肿瘤性脑炎抗体生物标志物：频率、年龄及性别关联
Autoimmune/Paraneoplastic Encephalitis Antibody Biomarkers: Frequency, Age, and Sex Associations.
作者信息
Kunchok Amy, McKeon Andrew, Zekeridou Anastasia, Flanagan Eoin P, Dubey Divyanshu, Lennon Vanda A, Klein Christopher J, Mills John R, Pittock Sean J
机构信息
Mellen Center, Neurological Institute, Cleveland Clinic, Cleveland, OH; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; Department of Neurology, Mayo Clinic, Rochester, MN; Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN; Department of Neurology, Mayo Clinic, Rochester, MN; Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic, Rochester, MN.
出版信息
Mayo Clin Proc. 2022 Mar;97(3):547-559. doi: 10.1016/j.mayocp.2021.07.023. Epub 2021 Dec 23.
OBJECTIVE
To determine the frequency of detection and the age and sex associations of autoimmune/paraneoplastic encephalitis antibody biomarkers (AE-Abs).
METHODS
There were 42,032 patients tested in the Mayo Clinic Neuroimmunology Laboratory between January 2018 and December 2019 for AE-Abs in serum or cerebrospinal fluid (CSF), including NMDA-R-IgG, AMPA-R-IgG, GABA-R-IgG, CASPR2-IgG, LGI1-IgG, GAD65-IgG, CRMP5-IgG, amphiphysin-IgG, PCA1/2/Tr-IgGs, ANNA1/2/3-IgGs, GFAP-IgG, mGluR1-IgG, DPPX-IgG, and MOG-IgG1. Results were examined to determine frequency of antibody positivity. Age and sex associations were examined by multivariable logistic regression.
RESULTS
Adult serum analysis (22,472 patients; 56% female) revealed that 814 (3.6%) were positive: NMDA-R-IgG (24.6%) > GAD65-IgG (21.5%) > LGI1-IgG (20.5%) > others. Of children (5649; 50% female), 251 (4.4%) were positive: NMDA-R-IgG (53.1%) > MOG-IgG1 (32%) > GAD65-IgG (7.1%) > others. Adult CSF analysis (18,745 patients; 54% female) revealed that 796 (4.2%) were positive: NMDA-R-IgG (39.7%) > GAD65-IgG (28.5%) > LGI1-IgG (11.4%) > others. Of children (5136; 50% female), 282 (5.5%) were positive: NMDA-R-IgG (88.1%) > GAD65-IgG (8.7%) > others. Age younger than 20 years was associated with NMDA-R-IgG and MOG-IgG1 (odds ratio [OR], 8.11 and 7.84, respectively; P<.001). Age older than 65 years was associated with GABA-R-IgG, LGI1-IgG, CASPR2-IgG, and ANNA1-IgG (OR, 7.33, 14.98, 3.67, and 14.53; P<.001). Women accounted for 60% of NMDA-R-IgG (CSF) and 78% of GAD65-IgG (CSF and serum) cohorts (OR, 1.32 [P=.002] and 2.23 [P<.001], respectively). Men accounted for 62% of the LGI1-IgG cohort (OR, 1.87; P<.001). Age and sex interacted for NMDA-R-IgG, particularly in female patients younger than 20 years (OR, 7.72; P<.001).
CONCLUSION
The most frequent AE-Abs detected were NMDA-R-IgG, GAD65-IgG, LGI1-IgG, and MOG-IgG1. Age and sex associations may suggest paraneoplastic, or aging influences on neurologic autoimmunity.
目的
确定自身免疫性/副肿瘤性脑炎抗体生物标志物（AE-Abs）的检测频率以及与年龄和性别的关联。
方法
2018年1月至2019年12月期间，梅奥诊所神经免疫学实验室对42,032例患者的血清或脑脊液（CSF）进行了AE-Abs检测，包括N-甲基-D-天冬氨酸受体免疫球蛋白G（NMDA-R-IgG）、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体免疫球蛋白G（AMPA-R-IgG）、γ-氨基丁酸受体免疫球蛋白G（GABA-R-IgG）、接触蛋白相关蛋白2免疫球蛋白G（CASPR2-IgG）、富含亮氨酸胶质瘤失活蛋白1免疫球蛋白G（LGI1-IgG）、谷氨酸脱羧酶65免疫球蛋白G（GAD65-IgG）、 collapsin反应调节蛋白5免疫球蛋白G（CRMP5-IgG）、抗 amphiphysin免疫球蛋白G、抗PCA1/2/Tr免疫球蛋白G、抗ANNA1/2/3免疫球蛋白G、抗胶质纤维酸性蛋白免疫球蛋白G（GFAP-IgG）、代谢型谷氨酸受体1免疫球蛋白G（mGluR1-IgG）、二肽基肽酶样蛋白6免疫球蛋白G（DPPX-IgG）和髓鞘少突胶质细胞糖蛋白免疫球蛋白G1（MOG-IgG1）。检查结果以确定抗体阳性频率。通过多变量逻辑回归分析年龄和性别关联。
结果
成人血清分析（22,472例患者；56%为女性）显示，814例（3.6%）呈阳性：NMDA-R-IgG（24.6%）>GAD65-IgG（21.5%）>LGI1-IgG（20.5%）>其他。儿童（5649例；50%为女性）中，251例（4.4%）呈阳性：NMDA-R-IgG（53.1%）>MOG-IgG1（32%）>GAD65-IgG（7.1%）>其他。成人脑脊液分析（18,745例患者；54%为女性）显示，796例（4.2%）呈阳性：NMDA-R-IgG（39.7%）>GAD65-IgG（28.5%）>LGI1-IgG（11.4%）>其他。儿童（5136例；50%为女性）中，282例（5.5%）呈阳性：NMDA-R-IgG（88.1%）>GAD65-IgG（8.7%）>其他。20岁以下年龄与NMDA-R-IgG和MOG-IgG1相关（优势比[OR]分别为8.11和7.84；P<0.001）。65岁以上年龄与GABA-R-IgG、LGI1-IgG、CASPR2-IgG和ANNA1-IgG相关（OR分别为7.33、14.98、3.67和14.53；P<0.001）。女性占NMDA-R-IgG（脑脊液）队列的60%和GAD65-IgG（脑脊液和血清）队列的78%（OR分别为1.32[P=0.002]和2.23[P<0.001]）。男性占LGI1-IgG队列的62%（OR为1.87；P<0.001）。年龄和性别在NMDA-R-IgG方面存在相互作用，尤其是在20岁以下的女性患者中（OR为7.72；P<0.001）。
结论
检测到的最常见AE-Abs为NMDA-R-IgG、GAD65-IgG、LGI1-IgG和MOG-IgG1。年龄和性别关联可能提示副肿瘤性或衰老对神经自身免疫的影响。
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