Lack of KIR4.1 autoantibodies in Japanese patients with MS and NMO

Abstract

Objectives:To examine anti-KIR4.1 antibodies by 2 different assays in Japanese patients with multiple sclerosis (MS) or neuromyelitis optica (NMO).Methods:One hundred sixty serum samples from 57 patients with MS, 40 patients with NMO/NMO spectrum disorder (NMOSD), and 50 healthy controls (all were Japanese) were tested with ELISA using a synthetic peptide of the first extracellular portion of human KIR4.1. In addition, we attempted to detect anti-KIR4.1 immunoglobulin G in the serum by the luciferase immunoprecipitation systems (LIPS) with the full length of human KIR4.1 produced in a human cell line, which is highly sensitive to single or multiple epitopes.Results:We failed to detect antibodies to the peptide fragment KIR4.183–120 in any case of MS and NMO/NMOSD using ELISA. Antibodies to the recombinant full length of KIR4.1 protein were detected in only 2 patients with MS and none in the patients with NMO/NMOSD by the LIPS assay.Conclusions:We developed 2 different methods (ELISA and LIPS) to measure autoantibodies to KIR4.1 in serum. We detected anti-KIR4.1 immunoglobulin G at a very low frequency in Japanese patients with MS or NMO/NMOSD. Serologic testing for human KIR4.1-specific antibodies is unlikely to improve the diagnosis of MS or NMO/NMOSD in Japanese patients.

Anti-KIR4.1 Antibodies in Chinese Patients with Central Nervous System Inflammatory Demyelinating Disorders

“…However, the presence of anti-KIR4.1 antibodies was detected in similar proportions of patients with OIND, OND, and healthy donors. Three previous studies [7,8,19] also showed low KIR4.1 antibody frequency in MS patients and controls. Higuchi et al [19] failed to detect antibodies to the peptide fragment KIR4.1 in any case of MS (57 patients) and NMOSD (40 patients) using ELI-SA.…”

“…Three previous studies [7,8,19] also showed low KIR4.1 antibody frequency in MS patients and controls. Higuchi et al [19] failed to detect antibodies to the peptide fragment KIR4.1 in any case of MS (57 patients) and NMOSD (40 patients) using ELI-SA. Antibodies to the recombinant full length of KIR4.1 protein were detected in only 2 patients with MS and none in the patients with NMOSD by the LIPS assay [19] .…”

“…Higuchi et al [19] failed to detect antibodies to the peptide fragment KIR4.1 in any case of MS (57 patients) and NMOSD (40 patients) using ELI-SA. Antibodies to the recombinant full length of KIR4.1 protein were detected in only 2 patients with MS and none in the patients with NMOSD by the LIPS assay [19] . Nerrant et al [7] reported that only 7.5% of 268 MS patients had anti-KIR4.1 antibodies and that this proportion did not significantly differ from that of healthy controls or patients with other neurologic diseases.…”

Autoantibodies in Pandemrix®-induced narcolepsy: Nine candidate autoantigens fail the conformational autoantibody test

“…Some studies have suggested, in opposite to the outlined hypocretin-neuron-specific degeneration for NT1, a broader immune reactivity against other areas of the brain [26,27]. Here, we test the autoantibody reactivity for NT1 patients against multiple sclerosis, as another HLA-DQB1 Ã 06:02-related neurological disorder, associated autoantigens ATP-dependent Inwardly Rectifying Potassium Channel (KIR4.1) [28][29][30][31][32][33][34][35][36] and calcium-activated chloride channel Anoctamin 2 (ANO2) [37].…”

KIR4.1: K+ Channel Illusion or Reality in the Autoimmune Pathogenesis of Multiple Sclerosis

“…Another recent study failed to detect enriched KIR4.1 autoantibodies in Japanese patents with MS (57 patients) or NMO (40 patients including NMO spectrum disorders), compared to 50 healthy controls (all were Japanese; Higuchi et al, 2016 ). ELISA using a synthetic peptide of the first extracellular portion of human KIR4.1 (residues 83–120) did not reveal even a single positive in serum samples from those patients.…”