# Principal Project

> **NIH NIH U19** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $334,000

## Abstract

Project Summary/Abstract
This project seeks to understand how T-B collaboration and specific autoantigens drive
inflammation and fibrosis in IgG4-related disease. In order to define antigenic drivers of IgG4-
related disease this proposal examines autoantigens that define IgG4-related disease. The
antigen-specificity of clonally expanded CD4+ cytotoxic T cells that are likely drivers of the
disease will also be determined. Cognate B cells will be identified in an antigen specific manner
and T and B cells interactions will be examined. Based on information on specific autoantigens
already obtained, autoantibodies and antigen specific B cells will be identified that are not only
seen initially at the time of diagnosis but that also return at the time of relapse following B cell
depletion induced remission. The autoantigens that dominate at the time of relapse are the likely
source of peptides that disease-related memory CD4+ T cells recognize. Autoantibodies will be
identified using HuProt protein arrays and validated by the Luciferase Immunoprecipitation
System assays and by ELISAs. Autoantigens will be dually labeled in order to identify and
characterize antigen-specific B cells. Overlapping peptides from key autoantigen proteins will be
used to activate autoantigen specific T cells, which will be characterized by flow cytometry and
transcriptomics. Mechanisms of inflammation and fibrosis driven by adaptive immune cells in
tissues will be characterized by imaging tissues and using systems biology approaches for
analysis.

## Key facts

- **NIH application ID:** 10844219
- **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:** $334,000
- **Award type:** 2
- **Project period:** 2014-05-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844219

## Citation

> US National Institutes of Health, RePORTER application 10844219, Principal Project (2U19AI110495-11). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10844219. Licensed CC0.

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