From the Department of Laboratory Medicine and Pathology, Neurology and Immunology (D.D., J.A.H., S.S., C.J.K., J.R.M., V.A.L., S.J.P., A.M.); Department of Neurology (D.D., J.A.H., S.S., C.J.K., J.R.M., V.A.L., S.J.P., A.M.), Mayo Clinic, Rochester, MN; and Euroimmun (L.K., S.B., C.P.), Lubeck, Germany.
Neurol Neuroimmunol Neuroinflamm. 2020 May 27;7(4). doi: 10.1212/NXI.0000000000000771. Print 2020 Jul.
To determine serologic characteristics, frequency, phenotype, paraneoplastic associations, and electrodiagnostic and histopathologic features accompanying contactin-1 autoimmunity.
Archived sera known to produce synaptic tissue-based immunofluorescence patterns were reevaluated, and contactin-1 specificity was confirmed by recombinant protein assays. Screening of 233 chronic/relapsing demyelinating neuropathies for additional cases was performed.
We identified 10 contactin-1 IgG seropositive cases. Frequency of contactin-1 immunoglobulin (Ig) G among tested Mayo Clinic chronic/relapsing demyelinating neuropathies was 2%. Sensory predominant presentations (n = 9, 90%), neuropathic pain (n = 6, 60%), and subacute progression (n = 5, 50%) were commonly encountered among contactin-1 neuropathies. Two patients had chronic immune sensory polyradiculopathy-like phenotype at presentation. Electrodiagnostic studies were consistent with demyelination (slowed conduction velocities and/or prolonged distal latencies) without conduction block. Markedly elevated CSF protein (median 222 mg/dL, range 69-960 mg/dL), thickening/gadolinium enhancement of nerve roots (4/5), and subperineural edema on nerve biopsy (4/4) were other characteristic features. Three cases were diagnosed with paraneoplastic demyelinating neuropathies (thymoma, n = 1; breast cancer, n = 1; plasmacytoma, n = 1). Four of the 9 patients treated with IV immunoglobulin demonstrated initial clinical improvement, but the favorable response was sustained in only 1 case (median follow-up, 60 months). Sustained clinical stabilization or improvement was observed among 3 of the 6 cases in whom second-line therapies (rituximab, cyclophosphamide, and azathioprine) were used.
Contactin-1 IgG has a distinct sensory predominant presentation commonly associated with neuropathic pain, with demyelinating changes on electrophysiologic studies. A paraneoplastic cause should be considered. Testing of contactin-1 IgG among cases with similar presentations may guide immunotherapy selection, especially second-line immunotherapy consideration.
确定伴随接触蛋白-1自身免疫的血清学特征、频率、表型、副肿瘤关联以及电诊断和组织病理学特征。
重新评估已知产生突触组织免疫荧光模式的存档血清，并通过重组蛋白检测确认接触蛋白-1的特异性。对 233 例慢性/复发性脱髓鞘性神经病进行了额外病例的筛查。
我们发现了 10 例接触蛋白-1 IgG 阳性病例。在测试的梅奥诊所慢性/复发性脱髓鞘性神经病中，接触蛋白-1 IgG 的频率为 2%。接触蛋白-1 神经病常见的表现为感觉为主（9 例，90%）、神经病理性疼痛（6 例，60%）和亚急性进展（5 例，50%）。两名患者在发病时表现为慢性免疫性感觉多神经根病样表型。电诊断研究符合脱髓鞘（传导速度减慢和/或远端潜伏期延长）而无传导阻滞。脑脊液蛋白显著升高（中位数 222mg/dL，范围 69-960mg/dL）、神经根增厚/钆增强（4/5）和神经活检的神经周围水肿（4/4）是其他特征性表现。3 例诊断为副肿瘤性脱髓鞘性神经病（胸腺瘤，1 例；乳腺癌，1 例；浆细胞瘤，1 例）。在接受 IV 免疫球蛋白治疗的 9 例患者中，有 4 例最初出现临床改善，但只有 1 例（中位随访时间 60 个月）的良好反应持续存在。在使用二线治疗（利妥昔单抗、环磷酰胺和硫唑嘌呤）的 6 例患者中，有 3 例观察到持续的临床稳定或改善。
接触蛋白-1 IgG 具有明显的感觉为主的表现，通常伴有神经病理性疼痛，电生理研究显示脱髓鞘改变。应考虑副肿瘤原因。在具有类似表现的患者中检测接触蛋白-1 IgG 可能有助于指导免疫治疗的选择，特别是二线免疫治疗的考虑。
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