T Follicular Helper like CD4+CXCR5+pd-1+ Cells and T Follicular Helper like Type 2 Cells Subsets Are Increased in IgG4-Related Disease Patients

Aurélie Grados¹, Mikael Ebbo¹, Christelle Piperoglou², Matthieu Groh³, Alexis Regent⁴, Maxime Samson⁵, Benjamin Terrier⁶, Nathalie Morel⁷, Sylvain Audia⁵, Francois Maurier⁸, Julie Graveleau⁹, Mohamed Hamidou¹⁰, Amandine Forestier¹¹, Sylvain Palat¹², Emanuelle Bernit¹, Gilles Kaplanski¹³, Frederique Retornaz¹⁴, Bernard Bonotte¹⁵, Catherine Farnarier¹⁶, Jean-Robert Harle¹⁷, Nathalie Costedoat-Chalumeau⁷, Frederic Vely¹⁸ and Nicolas Schleinitz¹, ¹Internal Medicine, Aix-Marseille Université, AP-HM, Marseille, France, ²Immunology, CIML, AP-HM, Marseille, France, ³National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, AP–HP, Université Paris Descartes, Paris, France, ⁴Service de médecine interne, Hôpital Cochin, Paris, France, ⁵Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, Dijon, France, ⁶Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Hôpital Cochin, Paris, France, ⁷Internal Medicine Department, Cochin Hospital, “René-Descartes Paris V” University, Paris, France, ⁸Medecine Interne, Metz, France, ⁹Medecine Interne Hotel Dieu Nantes, Nantes, France, ¹⁰Internal Medicine Department, Nantes University Hospital, Nantes, France, ¹¹Internal Medicine, Groupe Hospitalier Mutualiste de Grenoble, Grenoble, France, ¹²Service de Medecine Interne, CHU limoges, Limoges, France, ¹³Internal Medicine hopital conception, Aix-Marseille Université, Marseille, France, ¹⁴Conseil General 13 cellule recherche, Marseille, France, ¹⁵Department of Internal medicine and Clinicla Immunology Dijon University Hospital, Dijon, France, ¹⁶Laboratoire d'immunologie, Hopital de la Conception, Marseille, France, ¹⁷Internal Medicine, Aix-Marseille Université, APHM, Marseille, France, ¹⁸CIML, Laboratoire d'Immunologie Conception AP-HM, Aix-Marseille université, Marseille, France

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: IgG4 Related Disease, Plasmablasts, T cells and cytokines

Session Information

Date: Monday, November 9, 2015

Title: Miscellaneous Rheumatic and Inflammatory Diseases Oral Session II

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose:

IgG4 related disease (IgG4-RD) is associated with characteristic pathological changes including lymphoplasmocytic infiltration with abundant IgG4 positive plasma cells, storiform fibrosis and obliterative phlebitis. Recently an increase of plasmablasts in blood has been correlated with IgG4-RD activity. In IgG4-RD lesion tissues, germinal centers (GC) are often observed and could be source of plasmablasts. T follicular helper (Tfh) cells orchestrate antigen driven GC formation and B cell differentiation. Bona fide Tfh cells have been initially recognized in lymph nodes but a circulating counterpart characterized as Tfh like CD4⁺CXCR5⁺PD-1⁺ cells has been reported. We analyzed the Tfh like cells and their subsets in blood of untreated IgG4-RD patients.

Methods:

Thirty patients with IgG4-RD were included prospectively in the study and compared to matched (age and gender) healthy controls (HC) and matched (age) primary Sjögren syndrome (pSS) patients. Patients fulfilled the 2011 comprehensive IgG4-RD diagnostic criteria and the 2002 American-European Consensus Group criteria for pSS. Peripheral blood mononuclear cells (PBMC) of patients and controls were analyzed by flow cytometry on a BD FACS Canto II. Tfh like cells were defined as CD4⁺CXCR5⁺PD-1⁺. Subsets of Tfh were defined as Tfh2 CCR6^–CXCR3^- , Tfh-1 CCR6^–CXCR3⁺ and Tfh-17 CCR6⁺CXCR3^-. The cytokine production by PBMC for IL-4, IL-10 and IL-17 was performed with the cytokine bead assay (CBA® kit, BD Biosciences). Statistical analysis was performed on PRISM software.

Results: The frequency and absolute numbers (AN) of CD4⁺CXCR5⁺PD-1⁺Tfh like cells are increased in IgG4-RD when compared to HC (p<0,001) and pSS (p<0,001). In contrast the frequency (p=0.1) and AN (p=0.2) of CD4⁺CXCR5⁺ is not different from HC. Tfh-1 were decreased in IgG4-RD when compared to HC (p=0.0005) and pSS (p=0.002). Tfh-17 frequency only differed between IgG4-RD and pSS (p=0.04), increased in pSS. Tfh-2 were significantly increased in IgG4-RD when compred to HC (p<0.0001) and pSS (p=0.01). Tfh-2 values correlated with IgG4 serum levels (p=0.03) and IL-4 production by CBA assay (p=0.01) but not with IgG4-RD responder index (p=0.4) and plasmablasts numbers (p=0.1).

Conclusion: IgG4-related disease is associated with increased levels of T Follicular helper like CD4⁺CXCR5⁺PD-1⁺ cells in blood. The increase of Tfh like cells is mainly related to an increase of the Tfh2 CCR6^–CXCR3^- subset. These finding suggests that T follicular helper 2 cells, characterized by their ability to produce Th2 cytokines, play a role in IgG4-RD pathogenesis.

Disclosure: A. Grados, None; M. Ebbo, None; C. Piperoglou, None; M. Groh, None; A. Regent, None; M. Samson, None; B. Terrier, None; N. Morel, None; S. Audia, None; F. Maurier, None; J. Graveleau, None; M. Hamidou, None; A. Forestier, None; S. Palat, None; E. Bernit, None; G. Kaplanski, None; F. Retornaz, None; B. Bonotte, None; C. Farnarier, None; J. R. Harle, None; N. Costedoat-Chalumeau, None; F. Vely, None; N. Schleinitz, CSL behring Company France, 2,Roche France, 2,GlaxoSmithKline france, 2.

To cite this abstract in AMA style:

Grados A, Ebbo M, Piperoglou C, Groh M, Regent A, Samson M, Terrier B, Morel N, Audia S, Maurier F, Graveleau J, Hamidou M, Forestier A, Palat S, Bernit E, Kaplanski G, Retornaz F, Bonotte B, Farnarier C, Harle JR, Costedoat-Chalumeau N, Vely F, Schleinitz N. T Follicular Helper like CD4+CXCR5+pd-1+ Cells and T Follicular Helper like Type 2 Cells Subsets Are Increased in IgG4-Related Disease Patients [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/t-follicular-helper-like-cd4cxcr5pd-1-cells-and-t-follicular-helper-like-type-2-cells-subsets-are-increased-in-igg4-related-disease-patients/. Accessed .

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