SAT0222 COOPERATION OF T FOLLICULAR HELPER CELLS AND B CELLS IN TERTIARY LYMPHOID STRUCTURES IN TAKAYASU ARTERITIS

Abstract

Background: Takayasu’s arteritis (TA) and giant cell arteritis (GCA), the two most common types of large vessel vasculitis (LVV), are characterized by an arterial inflammatory granulomatous infiltrate mainly located in the media and the adventitia. However, distinct histological features of the immune response are poorly known. Objectives: To investigate distinct pathological mechanisms of the immune response in patients with GCA and TA. Methods: We performed comparative immunohistochemistry analysis of aorta of GCA and TA patients. We performed microarray gene analysis of purified CD4+ T cells of TA and GCA patients. Reverse transcriptase PCR, flow cytometry analysis and cell culture were used to investigate T and B cells subpopulations in 54 patients with TA, 52 with GCA and 60 controls. Results: We found higher proportion of tertiary lymphoid structures composed of CXCR5+, CD4+, PD-1+ and CD-20+ cells in inflammatory aortic lesions in TA as compared to GCA. We demonstrated increased proportion of aortic B cells in TA. We next evaluated differentiation of circulating CD4+ T cells in both diseases. Among sixty-seven genes differentially expressed in CD4+ T cells of TA compared to GCA patients, we identified a specific “T follicular helper” (Tfh) signature in TA patients. We also found a specific Tfh 17 signature in TA patients. Flow cytometry analysis confirmed increased circulating Tfh, defined as CXCR5+ CD4+ T cells, in TA patients as compared to GCA and healthy donors (HD) [median of 15.4 (10;30.8)% versus 5.3 (1.4; 12.2)% and 9.7 (5.6; 12.5)% (p Functionally, CXCR5+ CD4+ T cells of TA patients helped B cells to differentiate into memory cells, to proliferate and to secrete type G immunoglobulins. We sequenced the TCR repertoire α/β in CD3+CD4+CXCR5- and CD3+CD4+CXCR5+ cells, in aortic and blood samples from 2 patients. In both patients, we identified oligoclonal profile of TCR repertoire only for aortic CXCR5+ cells, suggesting antigenic selection of CXCR5+ CD4+ T cells. Conclusion: We provide evidence of the presence of tertiary lymphoid structures composed of Tfh and B cells in TA aorta. We identified a specific Tfh signature in circulating CD4+ T cells that distinguishes TA and GCA patients. The key cooperation of Tfh and B cells in TA and the oligoclonal repertoire of CXCR5+ CD4+ T cells strongly suggest the role of antigenic trigger. Disclosure of Interests: Anne-Claire DESBOIS Speakers bureau: SOBI en 2015, Anna Maciejewski-Duval: None declared, Paul Regnier: None declared, Valentin QUINIOU: None declared, Cloe Comarmond: None declared, Helene Vallet: None declared, Patrick Bruneval: None declared, Pierre Fouret: None declared, Michele Rosenzwajg: None declared, David Klatzmann: None declared, Fabien Koskas: None declared, Marlene Garrido: None declared, Guillaume Darrasse-Jeze: None declared, Patrice cacoub Consultant for: d’Abbvie, Astra Zeneca, Bayer, Boehringer Ingelheim, Gilead, Glaxo Smith Kline, Janssen, Merck Sharp Dohme, Pfizer, Roche, Servier, and Vifor., Speakers bureau: d’Abbvie, Astra Zeneca, Bayer, Boehringer Ingelheim, Gilead, Glaxo Smith Kline, Janssen, Merck Sharp Dohme, Pfizer, Roche, Servier, and Vifor., David Saadoun Grant/research support from: Roche, Abbvie, Consultant for: Janssen, Celgene, Abbvie, Roche