コンドウ タカユキ   KONDOU TAKAYUKI
  近藤 誉之
   所属   関西医科大学  神経内科学講座
   職種   診療教授
言語種別 英語
発表タイトル The increased expression of C5a receptor on peripheral blood B cells in NMOSD
会議名 第62回日本神経学会学術大会
学会区分 全国規模の学会
発表形式 口頭
講演区分 一般
発表者・共同発表者◎錦織隆成, 濱谷美緒, 芦田真士, 高田真基, 藤井ちひろ, 川村和之, 越智博文, 髙橋良輔, 上野英樹, 近藤誉之
発表年月日 2021/05/19
開催地
(都市, 国名)
京都
概要 [Objective]Anti-aquaporine-4 antibody is a causative antibody of more than 70% patients with neuromyelitis optica spectrum disorders (NMOSD). High therapeutic efficacy of eculizumab also confirmed the key role of complement cascades in NMOSD. Eculizumab inhibits cleavage reaction from C5 to C5a and C5b. Mechanisms of eculizumab are recognized to include prevention of membrane attack complex formation, C5b-9. In contrast, roles of C5a remains elusive despite observation on increased C5a in NMOSD-cerebrospinal-fluid. This study aims to reinforce importance of C5a in NMOSD by analyzing surface expression of its receptors, C5aR1 and C5aR2. [Methods]Peripheral blood mononuclear cells were isolated from 12 cases of seropositive NMOSD and 10 healthy subjects (HS). C5aR expression was analyzed by flow cytometry. [Results] The frequency of C5aR1 and C5aR2 expression (%C5aR1 and %C5aR2) was significantly upregulated in NMOSD compared with HC within B cells (remarkable examples: mean %C5aR1, 13.6% vs 4.8% and mean %C5aR2, 30.5% vs 20.7% within CD27+IgD- memory-B cells, %C5aR1, 12.8% vs 3.5%, %C5aR2, 28.7% vs 18.1% within CD27-IgD- DN-B). Higher %C5aR1 and %C5aR2 on memory-B and DN-B cells was observed during exacerbation without significance. Increased %C5aR2 on CD4+ and CD8+ T cells was found in NMOSD compared with HC (mean, 16.7% vs 11.9%; mean, 25.6% vs 17.5%,) but not %C5aR1. [Conclusions]Increased expression of C5aR on B cells and C5R2 on T cells in NMOSD suggests crucial roles of C5s in immuno-pathology of NMOSD.