Characterization of Lymphocytes Subsets in Peripheral Blood of Untreated 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 Bonotte⁵, Catherine Farnarier¹⁵, Jean-Robert Harle¹⁶, Nathalie Costedoat-Chalumeau⁷, Frederic Vely¹⁷ 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, ⁸HP Metz Belle Isle Hospital, Department of Internal Medicine, 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, ¹⁵Laboratoire d'immunologie, Hopital de la Conception, Marseille, France, ¹⁶Internal Medicine, Aix-Marseille Université, APHM, Marseille, France, ¹⁷CIML, 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: B cells, IgG4 Related Disease, T cells, T-Regulatory Cells and cytokines

Session Information

Date: Monday, November 9, 2015

Title: Miscellaneous Rheumatic and Inflammatory Diseases Poster Session II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

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. The etiology of the disease is unknown but a chronic antigen driven process leading to the production of IgG4 and IgG4⁺ plasmablasts is proposed. Various T cell subsets have been analyzed in the disease however in small studies. Their role remains unclear. We conducted a study to characterize peripheral blood immune cells subsets in patients with untreated IgG4-RD.

Methods:

Thirty patients with IgG4-RD were included prospectively in the study and compared to healthy controls (HC) and primary Sjögren syndrome (pSS) patients. Patients fulfilled the 2011 comprehensive IgG4-RD diagnostic criteria and the 2002 American-European Consensus Group criteria for pSS. PBMC of patients and controls were analyzed by flow cytometry on a BD FACS Canto II. T regulatory cells were characterized as CD4⁺ FoxP3⁺ CD25^highCD127^low, T cells were categorized as memory or naive by CD45RO and CD45RA expression, B cells were categorized as naive or switched memory by IgD and CD27 expression, plasmablasts were characterized as CD19⁺CD27^highCD38^high, dendritic cells were categorized as plasmacytoid or myeloid by CD11c and CD123 expression, NK cells were characterized as CD3^– CD56⁺CD16⁺.CD4⁺T helper subsets were analyzed after stimulation by intracellular staining for IL-4 (Th2), IFNg (Th1) and IL-17 (Th17). The cytokine production for IL-4, IL-10 and IL-17 was performed with the cytokine bead assay (CBA® kit, BD Biosciences) on supernatant of stimulated PBMC. Statistical analysis was performed on PRISM software.

Results:

The frequency and absolute number of total T cells, CD4⁺and CD8⁺T cells, CD45RA and CD45RO, total DC, T regulatory cells, NK cells, B and naive B cells did not show any changes between IgG4-RD patients and HC. pDC were decreased in IgG4-RD compared with HC (p=0.01) and pSS (p=0.01). Plasmablasts frequency (p=0.0003) and absolute numbers (p=0.0004) were increased in IgG4-RD patients when compared to HC. T helper subsets analysis showed an increase of Th2 cells (p=0.0004), Th17 cells (p=0.03) but not Th1 cells when compared to HC. The cytokine production by PBMC showed an increased release of IL-4 (p<0.0001), IL-10 (p=0.004) and IL-17 (p=0.001) by IgG4-RD compared to HC.

Conclusion: Baseline changes of immune cells in peripheral blood of IgG4-RD patients is characterized by plasmablast expansion, as previously reported, a decrease of plasmacytoid DC and a T helper switch to Th2 IL-4 producing cells. We also show an increase in IL-10 release and an increase of both Th17 cells and IL-17 release. Further studies are required to elucidate the role of these different subsets in the pathogenesis of IgG4-RD.

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. Characterization of Lymphocytes Subsets in Peripheral Blood of Untreated IgG4-Related Disease Patients [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/characterization-of-lymphocytes-subsets-in-peripheral-blood-of-untreated-igg4-related-disease-patients/. Accessed .

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