Takayuki Fujii1, Ryo Yamasaki1, Yukino Miyachi1, Kyoko Iinuma1, Yu Hashimoto1, Noriko Isobe1, Takuya Matsushita1, Jun-Ichi Kira2. 1. 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. 2. 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. kira@neuro.med.kyushu-u.ac.jp.
Abstract
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%, p = 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.
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 humanPlexin 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%, p = 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.