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

Abstract

Objectives: The aim of this study was to explore the frequency of KIR4.1 antibodies in patients with multiple sclerosis (MS) and in control groups using a cell-based assay. Materials and Methods: A transfected HEK-293A cell line expressing KIR4.1 was established to test for the presence of KIR4.1 antibodies in blood serum. We tested 904 subjects, including 188 patients with MS, 264 patients with neuromyelitis optica spectrum disorders (NMOSD), 209 patients with other inflammatory neurologic disease (OIND), 203 patients with other noninflammatory neurological disease (OND), and 40 healthy controls. Results: KIR4.1 antibodies were present in 23 of the 188 (12.2%) MS patients, 42 of the 264 (15.9%) NMOSD patients, 32 of the 209 (15.3%) OIND patients, 24 of the 203 (11.8%) OND patients, and 2 of the 40 (5%) healthy controls. There were no significant differences among the MS and control groups (p = 0.279). Conclusions: Anti-KIR4.1 antibody, as determined by a cell-based assay, is not a specific biomarker for MS.

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].…”

Anti-Kir4.1 Antibodies in Multiple Sclerosis: Specificity and Pathogenicity

“…In 2012, Srivastava et al screened serum samples aiming to identify CNS-specific antibodies in MS, and identified the glial potassium channel Kir4.1 as one of the serum immune targets in patients with MS. As aforementioned, antibodies against KIR4.1 were observed in 46.9% of the patients with MS, but were essentially absent in those with OND and HCs [14]. However, subsequent studies revealed controversial results, and were unable to confirm the value of KIR4.1 antibodies for an MS diagnosis [41][42][43][44][45][46][47][48][49][50][51]. We reviewed and summarized the prevalence of anti-Kir4.1 antibodies in patients with MS in 13 previous studies (Table 2).…”

“…These studies included 12 in adult patients and one in children. The studies were developed in the USA (3) [41][42][43], China (1) [44], France (1) [45], Germany (2) [14,40], Israel (1) [46], Italy (2) [47,48], Japan (2) [49,50], and Spain (1) [51]. Watanabe et al measured the anti-Kir4.1 antibodies by an enzyme-linked immunosorbent assay (ELISA) using a synthetic Kir4.1 83-120 peptide [49].…”

“…As per these criteria, we detected lower-glycosylated Kir4.1 antibodies in 28% of patients with MS and 5% of HCs. Subsequently, Zhong et al collected the sera from 188 patients with MS, 266 patients with NMO, 209 patients with other inflammatory neurological diseases, 203 patients with other noninflammatory neurological disease, and 40 HCs in China; they tried to detect the anti-Kir4.1 antibodies in patients with MS using a cell-based assay [44]. They observed 23/188 (12.2%) patients with MS, 42/264 (15.9%) patients with NMO, and 2/40 (5.0%) exhibited the anti-Kir4.1 antibodies.…”

“…Of the studies to date, four, including the original two studies by the Munich group, have demonstrated a positive association between the Kir4.1 antibodies and MS [14,40,44,47]. However, the KIR4.1 channel cannot currently be established as an important autoimmune target in MS diagnosis.…”