Characterization of Tissular T Follicular Helper Cells in IgG4-RD (TIFOLH4)

IgG4-related disease (IgG4-RD) is a recently identified rare disease characterized by inflammatory lesions with polyclonal lymphoplasmocytic infiltrate, with IgG4+ plasma cells predominance, and fibrosis in involved tissues. Despite a preferential involvement of exocrine organs, virtually all tissues can be affected by the disease. Corticosteroids are usually effective in this indication, but with poor tolerance and a high risk of relapse after decrease or withdrawal of this treatment. In this context, identification of new therapeutic targets is a major concern for these patients. Physiopathology of IgG4-RD remains actually unknown. In previous studies, it has been shown that T follicular Helper (Tfh) cells are expanded in the blood of these patients. Tfh cells have an important role in the formation of germinal centers (GCs), and ectopic GCs have been found in tissues of patients with IgG4-RD. Tfh cells have a major role in proliferation and differentiation of B cell compartment. In this context, this population could have an important contribution in the pathophysiology of IgG4-RD and could represent a therapeutic target in this disease.

TIFOLH4 study intend to analyze tissue Tfh cells in patients with IgG4-RD at diagnosis. This study is an exploratory prospective multicentric study. Thirty patients with a suspected diagnosis of IgG4-RD, because of 1 or more suggestive organ involved, will be included in the study. A 50 mL blood sample and a biopsy, obtained in the same time of the diagnostic biopsy sample, will be obtained in this study. The results obtained in patients with a confirmed diagnosis of IgG4-RD (" IgG4-RD group ") will be compared to results of patients with another diagnosis (" control group "). Main objective of the study is to show by confocal microscopy an expansion of the number of Tfh cells (CD3+CD4+PD1+ cells) in tissue of IgG4-RD patients compared to controls. Secondary objectives include : tissue analysis of Tfh subsets (Tfh1, Tfh2 and Tfh17) ; tissue analysis of B regulatory cells, T regulatory cells, and T helper cells (Th1, Th2, Th17); correlation between tissue and circulating biomarkers; tissue proteomic analysis; and functional analysis of circulating Tfh cells after sorting of these cells and co-culture tests with autologous naive B cells. All these results will be compared between the " IgG4-RD group " and the " control group ". This study should clarify the role of these Tfh populations in IgG4-RD, identify diagnostic tissue and blood biomarkers, and identify therapeutic targets in these patients.

Study Overview

• Status: Completed
• Conditions: Disease Immunoglobulin G4
• Intervention / Treatment: Biological: blood sample

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mikael EBBO, Doctor; Phone Number: 0491388831; Email: mikael.ebbo@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13354
    • Assistance Publique Hopitaux de Marseille
    • Contact: Mikael EBBO, Doctor; Phone Number: 0491388831; Email: mikael.ebbo@ap-hm.fr
    • Principal Investigator: Mikael EBBO, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient with a diagnosis of disease associated with IgG4
• Patient signed a consent
• Patient affiliated to the social security scheme

Exclusion Criteria:

• Patients with a corticosteroid therapy current or less than 3 months.
• Patients with an immunosuppressive treatment or being less than 3 months
• Patients with a biotherapy treatment by ongoing or less 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: diagnosis of disease associated with IgG4; patients suffering from organ initially compatible with a diagnosis of a disease associated with IgG4	Biological: blood sample; One blood sample of 50 milliliter 24 hours after the inclusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Location of TFH cells by immunofluorescence technical	Ratio of TFH cell on the number of total T lymphocytes by high power field in confocal microscopy in tissues of patients	36 months

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2018
• Primary Completion (Actual): February 8, 2021
• Study Completion (Actual): February 8, 2021

Study Registration Dates

• First Submitted: August 16, 2016
• First Submitted That Met QC Criteria: August 16, 2016
• First Posted (Estimated): August 19, 2016

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Immunoglobulin G4-Related Disease
• Other Study ID Numbers: 2016-28; 2016-A00943-48 (Registry Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No