Pro-fibrotic role of IgG4 antibodies in the pathogenesis of IgG4-related disease

Concept

IgG4-related disease (IgG4RD) is a fibrotic disorder of unknown etiology named for the peculiar accumulation of IgG4 antibodies in affected organs. Depletion of IgG4 producing B-lymphocytes after treatment with rituximab reverses myofibroblast activation in affected tissues suggesting that B-lymphocytes and IgG4 antibodies might directly contribute to tissue fibrosis in this condition.
The project will demonstrate overlooked fibrotic properties of IgG4 antibodies and to explore the therapeutic potential of their inhibition.

Facts and Figures

Project lead
E Della Torre
San Raffaele Hospital (SRH)
dellatorre.emanuel@hsr.it
FOREUM research grant € 200'000
2021 - 2024

Meet the Team

E Della Torre
San Raffaele Hospital (SRH)
S Ostuzzi
ALOMAR Associazione Lombarda Malati Reumatici
I Galetti
Gruppo Italiano Lotta alla Sclerodermia (GILS)
A Vieira
Liga Portuguesa Contra as Doenças Reumáticas
V Guimaraes
Liga Portuguesa Contra as Doenças Reumáticas

Objectives

With the present research project we aim:
1. to demonstrate a direct pro-fibrotic effect of IgG4 antibodies from IgG4RD patients
2. to identify fibrotic molecular properties of IgG4 antibodies from IgG4RD patients
3. to explore the therapeutic potential of inhibiting the pro-fibrotic activity of IgG4 antibodies
In addition, the project will include a parallel work package conceived to engage patients over and beyond voluntary sample donation and discussion of scientific outputs. In particular, we will take advantage of this FOREUM Call and collaborate with  experienced PRP in order to:
4. to identify IgG4RD specific “patient reported outcomes” (PRO) and develop the first ad hoc QoL questionnaire for IgG4RD (IgG4RD QoL).

Patient Voice

By implementing a patient-specific “work package”, our study will actively involve experienced Patient Research Partners and a large number of patients with IgG4RD in the full research project. This ideal enterprise will proficiently raise
awareness on clinical and psychological instances that have never been systematically addressed before in IgG4RD, thus outlining a new era of personalized medical care tailored on patients’ needs and based on targeted therapeutic approaches.

Goals/Milestones

Milestone 1: Demonstration of a pro-fibrotic effect of IgG or IgG subclasses
Milestone 2: Identification of fibrotic molecular properties of IgG or IgG subclasses
Milestone 3: Identification of novel possible therapeutic targets
Milestone 4: Development of a Quality of Life Questionnaire for IgG4RD