与抗 Plexin D1 抗体相关的三叉神经痛
Painful trigeminal neuropathy associated with anti-Plexin D1 antibody.
机构信息
From the Department of Neurological Therapeutics (T.F., N.I.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka; Department of Neurology (R.Y., Y.M., K.I., Y.H., T.M., J.K.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka; Translational Neuroscience Center (J.K.), Graduate School of Medicine, and School of Pharmacy at Fukuoka, International University of Health and Welfare, Ookawa, Fukuoka; and Department of Neurology (J.K.), Brain and Nerve Center, Fukuoka Central Hospital, International University of Health and Welfare, Chuou-ku, Japan.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2020 Jun 25;7(5). doi: 10.1212/NXI.0000000000000819. Print 2020 Sep.
OBJECTIVE
To determine whether anti-Plexin D1 antibody (Plexin D1-immunoglobulin G [IgG]), which is associated with limb and trunk neuropathic pain (NP) and binds to pain-conducting small unmyelinated dorsal root ganglion (DRG) neurons, exists in patients with idiopathic painful trigeminal neuropathy (IPTN) and whether Plexin D1-IgG binds to trigeminal ganglion (TG) neurons.
METHODS
We enrolled 21 consecutive patients with IPTN and 35 age- and sex-matched controls without NP (25 healthy persons and 10 with neurodegenerative diseases). We measured serum Plexin D1-IgG using a mouse DRG tissue-based indirect immunofluorescence assay (IFA) and by Western blotting (WB) using a recombinant human Plexin D1 (rhPlexin D1) accompanied by immunoadsorption tests with rhPlexin D1. The reactivity of Plexin D1-IgG toward mouse TG, brain, heart, and kidney was assessed by tissue-based IFAs.
RESULTS
Serum Plexin D1-IgG was detected more frequently in IPTN than in controls by both IFA and WB (14.3% vs 0%, = 0.048). Three Plexin D1-IgG-positive patients also had limb or trunk NP and commonly showed tongue pain. In tissue-based IFAs, IgG from 2 Plexin D1-IgG-positive patients immunostained small TG neurons, which was prevented by preincubation with rhPlexin D1. Moreover, Plexin D1-IgG immunostaining mostly colocalized with isolectin B4-positive pain-conducting unmyelinated TG neurons. IFAs of other tissues with the same IgG revealed weak immunoreactivity only in endothelial cells, which was prevented by preincubation with rhPlexin D1.
CONCLUSIONS
Plexin D1-IgG, which binds to pain-conducting small TG neurons in addition to DRG neurons, can be present in IPTN as well as limb and trunk NP.
目的
确定与肢体和躯干神经性疼痛（NP）相关并与痛觉传导的小无髓鞘背根神经节（DRG）神经元结合的抗 Plexin D1 抗体（Plexin D1-免疫球蛋白 G [IgG]）是否存在于特发性三叉神经痛性神经病（IPTN）患者中，以及 Plexin D1-IgG 是否与三叉神经节（TG）神经元结合。
方法
我们招募了 21 例连续的 IPTN 患者和 35 名年龄和性别匹配的无 NP 对照组患者（25 名健康人和 10 名神经退行性疾病患者）。我们使用基于小鼠 DRG 的间接免疫荧光测定法（IFA）和使用重组人 Plexin D1（rhPlexin D1）的 Western blot （WB）测量血清 Plexin D1-IgG，同时进行 rhPlexin D1 免疫吸附试验。通过基于组织的 IFA 评估 Plexin D1-IgG 对小鼠 TG、脑、心脏和肾脏的反应性。
结果
通过 IFA 和 WB，我们发现 IPTN 患者血清 Plexin D1-IgG 的检出率高于对照组（14.3%比 0%，=0.048）。3 例 Plexin D1-IgG 阳性患者也有肢体或躯干 NP，且常伴有舌痛。在基于组织的 IFA 中，来自 2 例 Plexin D1-IgG 阳性患者的 IgG 免疫染色了小 TG 神经元，该染色可被 rhPlexin D1 预孵育所阻断。此外，Plexin D1-IgG 免疫染色主要与 isolectin B4 阳性痛觉传导无髓 TG 神经元共定位。用相同 IgG 进行的其他组织 IFA 仅显示弱免疫反应性，仅存在于内皮细胞中，该反应性可被 rhPlexin D1 预孵育所阻断。
结论
除了 DRG 神经元外，还可以与痛觉传导的小 TG 神经元结合的 Plexin D1-IgG 可能存在于 IPTN 以及肢体和躯干 NP 中。
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