title: T Cell Polarization toward TH2/TFH2 and TH17/TFH17 in Patients with IgG4-Related Disease.
abstract: IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder involving virtually every organ with a risk of organ dysfunction. Despite recent studies regarding B cell and T cell compartments, the disease's pathophysiology remains poorly understood. We examined and characterized subsets of circulating lymphocytes in untreated patients with active IgG4-RD. Twenty-eight consecutive patients with biopsy-proven IgG4-RD were included in a prospective, multicentric study. Lymphocytes' subsets were analyzed by flow cytometry, with analysis of TH1/TH2/TH17, TFHcells, and cytokine release by peripheral blood mononuclear cells. Results were compared to healthy controls and to patients with primary Sjögren's syndrome. Patients with IgG4-RD showed an increase of circulating T regulatory, TH2, TH17, and CD4+CXCR5+PD1+TFHcell subsets. Accordingly, increased levels of IL-10 and IL-4 were measured in IgG-RD patients. TFHincrease was characterized by the specific expansion of TFH2 (CCR6-CXCR3-), and to a lesser extent of TFH17 (CCR6+CXCR3-) cells. Interestingly, CD4+CXCR5+PD1+TFHcells normalized under treatment. IgG4-RD is characterized by a shift of circulating T cells toward a TH2/TFH2 and TH17/TFH17 polarization. This immunological imbalance might be implicated in the disease's pathophysiology. Treatment regimens targeting such T cells warrant further evaluation.
authors.affiliation: AP-HM, Service de Médecine Interne, Hôpital de la Timone, Marseille, France; Aix-Marseille Université, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Grados
authors.affiliation: AP-HM, Service de Médecine Interne, Hôpital de la Timone, Marseille, France; Aix-Marseille Université, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
authors.forename: Mikael
authors.initials: M
authors.lastname: Ebbo
authors.affiliation: Aix-Marseille Université, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France; AP-HM, Service d'Immunologie, Hôpital de la Conception, Marseille, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Piperoglou
authors.affiliation: Service de Médecine Interne, CHU Cochin, AP-HP, Paris, France; Université Paris Descartes, Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Groh
authors.affiliation: Service de Médecine Interne, CHU Cochin, AP-HP, Paris, France; Université Paris Descartes, Paris, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Regent
authors.affiliation: Service de Médecine Interne, CHU le Bocage, Dijon, France; Université de Bourgogne, Dijon, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Samson
authors.affiliation: Service de Médecine Interne, CHU Cochin, AP-HP, Paris, France; Université Paris Descartes, Paris, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Terrier
authors.affiliation: AP-HM, Unité d'Aide Méthodologique, Aix-Marseille Université , Marseille , France.
authors.forename: Anderson
authors.initials: A
authors.lastname: Loundou
authors.affiliation: Service de Médecine Interne, CHU Cochin, AP-HP, Paris, France; Université Paris Descartes, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Morel
authors.affiliation: Service de Médecine Interne, CHU le Bocage, Dijon, France; Université de Bourgogne, Dijon, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Audia
authors.affiliation: Service de Médecine Interne, Hôpital Sainte Blandine , Metz , France.
authors.forename: François
authors.initials: F
authors.lastname: Maurier
authors.affiliation: Service de Médecine Interne, CHU de Nantes, Nantes, France; Université de Nantes, Nantes, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Graveleau
authors.affiliation: Service de Médecine Interne, CHU de Nantes, Nantes, France; Université de Nantes, Nantes, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hamidou
authors.affiliation: Service d'Immunologie clinique, Groupe hospitalier mutualiste , Grenoble , France.
authors.forename: Amandine
authors.initials: A
authors.lastname: Forestier
authors.affiliation: Service de Médecine Interne, CHU Dupuytren , Limoges , France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Palat
authors.affiliation: AP-HM, Service de Médecine Interne, Hôpital de la Timone , Marseille , France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bernit
authors.affiliation: Service de Médecine Interne, CHU le Bocage, Dijon, France; Université de Bourgogne, Dijon, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Bonotte
authors.affiliation: AP-HM, Service d'Immunologie, Hôpital de la Conception , Marseille , France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Farnarier
authors.affiliation: AP-HM, Service de Médecine Interne, Hôpital de la Timone, Marseille, France; Aix-Marseille Université, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
authors.forename: Jean-Robert
authors.initials: JR
authors.lastname: Harlé
authors.affiliation: Service de Médecine Interne, CHU Cochin, AP-HP, Paris, France; Université Paris Descartes, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Costedoat-Chalumeau
authors.affiliation: Aix-Marseille Université, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France; AP-HM, Service d'Immunologie, Hôpital de la Conception, Marseille, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Vély
authors.affiliation: AP-HM, Service de Médecine Interne, Hôpital de la Timone, Marseille, France; Aix-Marseille Université, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Schleinitz
keywords: IgG4-related disease; Sjögren’s syndrome; T follicular helper cells; T helper cells; plasmablasts