Tobin William Oliver, Lennon Vanda A, Komorowski Lars, Probst Christian, Clardy Stacey Lynn, Aksamit Allen J, Appendino Juan Pablo, Lucchinetti Claudia F, Matsumoto Joseph Y, Pittock Sean J, Sandroni Paola, Tippmann-Peikert Maja, Wirrell Elaine C, McKeon Andrew
From the Departments of Neurology (W.O.T., V.A.L., S.L.C., A.J.A., C.F.L., J.Y.M., S.J.P., P.S., M.T.-P., E.C.W., A.M.), Laboratory Medicine and Pathology (V.A.L., S.J.P., A.M.), Immunology (V.A.L.), and Pediatrics (E.C.W.), College of Medicine, Mayo Clinic, Rochester, MN; Euroimmun AG (L.K., C.P.), Lübeck, Germany; and Neurology (J.P.A.), Faculty of Medicine, University of Manitoba, Canada.
Neurology. 2014 Nov 11;83(20):1797-803. doi: 10.1212/WNL.0000000000000991. Epub 2014 Oct 15.
To describe the detection frequency and clinical associations of immunoglobulin G (IgG) targeting dipeptidyl-peptidase-like protein-6 (DPPX), a regulatory subunit of neuronal Kv4.2 potassium channels.
Specimens from 20 patients evaluated on a service basis by tissue-based immunofluorescence yielded a synaptic immunostaining pattern consistent with DPPX-IgG (serum, 20; CSF, all 7 available). Transfected HEK293 cell-based assay confirmed DPPX specificity in all specimens. Sixty-nine patients with stiff-person syndrome and related disorders were also evaluated by DPPX-IgG cell-based assay.
Of 20 seropositive patients, 12 were men; median symptom onset age was 53 years (range, 13-75). Symptom onset was insidious in 15 and subacute in 5. Twelve patients reported prodromal weight loss. Neurologic disorders were multifocal. All had one or more brain or brainstem manifestations: amnesia (16), delirium (8), psychosis (4), depression (4), seizures (2), and brainstem disorders (15; eye movement disturbances [8], ataxia [7], dysphagia [6], dysarthria [4], respiratory failure [3]). Nine patients reported sleep disturbance. Manifestations of central hyperexcitability included myoclonus (8), exaggerated startle (6), diffuse rigidity (6), and hyperreflexia (6). Dysautonomia involved the gastrointestinal tract (9; diarrhea [6], gastroparesis, and constipation [3]), bladder (7), cardiac conduction system (3), and thermoregulation (1). Two patients had B-cell neoplasms: gastrointestinal lymphoma (1), and chronic lymphocytic leukemia (1). Substantial neurologic improvements followed immunotherapy in 7 of 11 patients with available treatment data. DPPX-IgG was not detected in any of the stiff-person syndrome patients.
DPPX-IgG is a biomarker for an immunotherapy-responsive multifocal neurologic disorder of the central and autonomic nervous systems.
描述靶向二肽基肽酶样蛋白6（DPPX，神经元Kv4.2钾通道的一个调节亚基）的免疫球蛋白G（IgG）的检测频率及临床相关性。
对20例基于组织免疫荧光进行评估的患者样本进行检测，其突触免疫染色模式与DPPX-IgG一致（血清样本20份；脑脊液样本7份，均可用）。基于转染HEK293细胞的检测方法证实了所有样本中DPPX的特异性。还对69例僵人综合征及相关疾病患者进行了基于DPPX-IgG细胞的检测。
20例血清阳性患者中，男性12例；症状中位起病年龄为53岁（范围13 - 75岁）。15例起病隐匿，5例亚急性起病。12例患者报告前驱期体重减轻。神经系统疾病为多灶性。所有患者均有一个或多个脑或脑干表现：失忆（16例）、谵妄（8例）、精神病（4例）、抑郁（4例）、癫痫发作（2例）和脑干疾病（15例；眼球运动障碍[8例]、共济失调[7例]、吞咽困难[6例]、构音障碍[4例]、呼吸衰竭[3例]）。9例患者报告有睡眠障碍。中枢性兴奋亢进的表现包括肌阵挛（8例）、惊吓反应增强（6例）、弥漫性僵硬（6例）和反射亢进（6例）。自主神经功能障碍累及胃肠道（9例；腹泻[6例]、胃轻瘫和便秘[3例]）、膀胱（7例）、心脏传导系统（3例）和体温调节（1例）。2例患者患有B细胞肿瘤：胃肠道淋巴瘤（1例）和慢性淋巴细胞白血病（1例）。在11例有可用治疗数据的患者中，7例在免疫治疗后神经功能有显著改善。在任何僵人综合征患者中均未检测到DPPX-IgG。
DPPX-IgG是一种对免疫治疗有反应的中枢和自主神经系统多灶性神经疾病的生物标志物。
