Abstract
The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients. Hematoxylin and eosin-stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry. Immune cells from the adventitial layer of one patient were characterized by flow cytometry. Demographic, medical history, laboratory, imaging, treatment, and follow-up data were extracted from medical records. Aorta specimens from Bentall procedures were available from seven patients (5 females, aged 22-57 years) with TA. Surgical treatment was performed at TA diagnosis (n = 4) or at a median of 108 months (84-156) after TA diagnosis. Disease was active at surgery in four patients according to NIH score. B cell aggregates-TLOs containing HEVs were observed in the adventitia of all but one patient. Of note, ectopic follicles containing CD21(+) FDCs were found in all patients (4/4) with increased aortic (18)F-fluoro-deoxyglucose (FDG) uptake before surgery but were absent in all but one patients (2/3) with no FDG uptake. In addition, flow cytometry analysis confirmed the accumulation of memory/germinal center-like B cells in the adventitial layer and showed the presence of antigen-experienced T follicular helper cells. Ectopic lymphoid neogenesis displaying functional features can be found in the aortic wall of a subset of patients with active TA. The function of these local B cell clusters on the pathogenesis of TA remains to be elucidated.
Highlights
Takayasu arteritis (TA) is a rare primary vasculitis affecting large arteries, especially the aorta, the aortic arch, and its main branches
Takayasu arteritis is a rare form of chronic large vessel vasculitis of unknown origin involving the aorta and its major branches
Our data show that ectopic lymphoid neogenesis takes place in the aortic wall of patients with active TA and highlight the role of B cells in TA
Summary
Takayasu arteritis (TA) is a rare primary vasculitis affecting large arteries, especially the aorta, the aortic arch, and its main branches. While T cells exhibiting a Th1 profile have been implicated in the pathogenesis of TA [1, 2], the role of humoral immunity remains to be elucidated. TLOs have morphologic features of secondary lymphoid organs including post-capillary high endothelial venules (HEVs) allowing homing of naive cells in the T cell area, an interface between T and B cell zones and germinal center (GC) areas. Studies have pinpointed the presence of lymphoid aggregates in the aortic wall of TA patients without distinguishing them from granulomas and have suggested their implication in the physiopathology of TA [6, 7]. Pathogenic B cells producing autoantibodies against endothelial cells are found in the blood stream of active TA patients, which suggests that these B cells could be activated within the adventitial layer before recirculating [8]. Some TA patients with active disease have a dramatic increase of circulating plasmablasts that are efficiently targeted by depleting anti-CD20 antibodies [9]
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