# An autoimmune center of excellence for the study of IgG4-related disease

> **NIH NIH U19** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $774,410

## Abstract

Project Summary/Abstract
This proposal focuses on the study of IgG4-related disease in part to obtain insights about the
underlying mechanisms that specifically initiate and help maintain this disease. However, the
broader goal is to leverage unusual and “advantageous” aspects of this disease to gain broader
insights about the underlying principles and mechanisms that potentially lead to the initiation
and maintenance of many human autoimmune disorders, in a more general sense. The
indolent nature of IgG4-related disease is a factor behind why patients are typically initially seen
in an untreated state. The dramatic response to B cell depletion therapy allows easy follow-up
up to and at the time of remission and the regular systematic follow up of patients allows us to
investigate these patients as they relapse many months later. Sequential analyses will be
performed sequentially on peripheral blood mononuclear cells, serum and on the stool (for
microbiome). We will use Protein arrays, ELISAs and Luciferase Immunoprecipitation Systems
assays to help categorize patients according to their auto-antibody profiles, identify antigen
specific B cells and use overlapping peptides to identify memory T cells against self-antigens
that induce T-B collaboration and potentially drive the initial disease and the relapse. Potential
cross-reactivity of microbial peptide specific CD4+ T cell for self-antigens will also be assessed.
Tissue interrogation approaches that incorporate systems biology tools will be used to examine
disease end organs to better understand immune mechanisms that drive fibrosis, and when
possible draining lymph nodes, to attempt to understand immune dysregulation events that may
help initiate the disease.

## Key facts

- **NIH application ID:** 10844211
- **Project number:** 2U19AI110495-11
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** SHIV Subramaniam PILLAI
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $774,410
- **Award type:** 2
- **Project period:** 2014-05-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844211

## Citation

> US National Institutes of Health, RePORTER application 10844211, An autoimmune center of excellence for the study of IgG4-related disease (2U19AI110495-11). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10844211. Licensed CC0.

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