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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.

Painful trigeminal neuropathy associated with anti-Plexin D1 antibody