PT  - JOURNAL ARTICLE
AU  - Yohei Yamamoto
AU  - Naoko Matsui
AU  - Akiyuki Uzawa
AU  - Yukiko Ozawa
AU  - Tetsuya Kanai
AU  - Fumiko Oda
AU  - Hiroyuki Kondo
AU  - Izumi Ohigashi
AU  - Hiromitsu Takizawa
AU  - Kazuya Kondo
AU  - Mikio Sugano
AU  - Takashi Kitaichi
AU  - Hiroki Hata
AU  - Ryuji Kaji
AU  - Satoshi Kuwabara
AU  - Takashi Yamamura
AU  - Yuishin Izumi
TI  - Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease
AID  - 10.1212/NXI.0000000000001087
DP  - 2021 Nov 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e1087
VI  - 8
IP  - 6
4099  - http://nn.neurology.org/content/8/6/e1087.short
4100  - http://nn.neurology.org/content/8/6/e1087.full
SO  - Neurol Neuroimmunol Neuroinflamm2021 Nov 01; 8
AB  - Background and Objectives To investigate intrathymic B lymphopoiesis in patients with myasthenia gravis (MG) and explore thymus pathology associated with clinical impact.Methods Thymic lymphocytes from 15 young patients without MG, 22 adult patients without MG, 14 patients with MG without thymoma, and 11 patients with MG with thymoma were subjected to flow cytometry analysis of T follicular helper (Tfh), naive B, memory B, plasmablasts, CD19+B220high thymic B cells, B-cell activating factor receptor, and C-X-C chemokine receptor 5 (CXCR5). Peripheral blood mononuclear cells of 16 healthy subjects and 21 untreated patients with MG were also analyzed. Immunologic values were compared, and correlations between relevant values and clinical parameters were evaluated.Results The frequencies of circulating and intrathymic plasmablasts were significantly higher in patients with MG than controls. On the other hand, the frequency of CD19+B220high thymic B cells was not increased in MG thymus. We observed a significant increase in CXCR5 expression on plasmablasts in MG thymus and an increased frequency of intrathymic plasmablasts that was correlated with preoperative disease activity. The frequency of intrathymic Tfh cells was significantly lower in patients who received immunosuppressive (IS) therapy than those without IS therapy. However, there was no significant difference in the frequency of intrathymic plasmablasts irrespective of IS therapy.Discussion Our findings confirmed a correlation between increased frequency of intrathymic plasmablasts and disease activity before thymectomy. We postulate that activated intrathymic plasmablasts endow pathogenic capacity in MG.AChR=acetylcholine receptor; ADL=activities of daily living; BAFF-R=B-cell activating factor receptor; CXCR5=C-X-C chemokine receptor 5; GC=germinal center; HS=healthy subjects; IS=immunosuppressive; MFI=mean fluorescence intensity; MG=myasthenia gravis; PMBC=peripheral blood mononuclear cell; Tfh=T follicular helper; TFH=thymic follicular hyperplasia; TNF=tumor necrosis factor