RT Journal Article
SR Electronic
T1 Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e1087
DO 10.1212/NXI.0000000000001087
VO 8
IS 6
A1 Yohei Yamamoto
A1 Naoko Matsui
A1 Akiyuki Uzawa
A1 Yukiko Ozawa
A1 Tetsuya Kanai
A1 Fumiko Oda
A1 Hiroyuki Kondo
A1 Izumi Ohigashi
A1 Hiromitsu Takizawa
A1 Kazuya Kondo
A1 Mikio Sugano
A1 Takashi Kitaichi
A1 Hiroki Hata
A1 Ryuji Kaji
A1 Satoshi Kuwabara
A1 Takashi Yamamura
A1 Yuishin Izumi
YR 2021
UL http://nn.neurology.org/content/8/6/e1087.abstract
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