# Pathobiology of ANCA Glomerulonephritis: Targeting Adaptive and Innate Immune Processes for Precision Therapies

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $678,823

## Abstract

ABSTRACT
 Anti-neutrophil cytoplasmic autoantibodies (ANCA) glomerulonephritis (GN) is a life-threatening
autoimmune disease. While current immunosuppressive agents produce remission in the majority of patients,
our treatment has had precision more akin to a chainsaw rather than a scalpel. The lack of specific, targeted
immune therapy leaves patients with an overly handicapped immune system and a host of toxic side effects. Our
proposal seeks to to finally advance the field toward more precise and targeted therapies with far less potential
for harm.
 Building upon our prior body of work, we will attempt to exploit the adaptive autoimmune responses seen
in ANCA GN as targets for immunomodulatory therapies by multiple approaches. By using our previously
developed epitope mapping techniques, we will engineer chimeric autoantibody receptor (CAAR) T cells that will
specifically target only those B cells that express the pathogenic ANCA antibody epitopes. In another approach,
we will profile the heterogeneous population of T regulatory cells. After identifying those that are fully
suppressive, we will attempt to expand this population in vitro and confirm that they retain their suppressive
function. This work will determine whether in future studies, we can first harvest these cells from ANCA GN
patients, expand them in vitro, and reintroduce them into patients to provide immunomodulatory effects that
would reintroduce autoimmune tolerance. Utilizing our well-characterized mouse model of myeloperoxidase
(MPO) ANCA GN, we will explore the mechanisms by which T (and B) regulatory cells suppress autoimmunity
and leverage this knowledge to develop pre-clinical models of T regulatory cell therapy.
 In addition to the potential role of cell-based therapies, we will explore the role of the innate immune
system in ANCA GN using our established MPO mouse model and novel models that we have developed of
granulomatous disease. These models will also us to identify components of the innate immune response that
may be amenable to novel therapies. Further, we will determine whether we can manipulate the epigenetic
changes that alter expression of the autoantigen proteins targeted by the autoimmune processes that drive
ANCA GN.
 These foundational studies have been designed with the intent to inform Investigative New Drug (IND)
applications to the Food and Drug Administration (FDA). This work will usher in a new therapeutic era for ANCA
GN, characterized by greater precision, less toxicity and perhaps, longer duration.

## Key facts

- **NIH application ID:** 10029222
- **Project number:** 1R01DK125350-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** DOMINIC J CIAVATTA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $678,823
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10029222

## Citation

> US National Institutes of Health, RePORTER application 10029222, Pathobiology of ANCA Glomerulonephritis: Targeting Adaptive and Innate Immune Processes for Precision Therapies (1R01DK125350-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10029222. Licensed CC0.

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