# Elucidating IgA nephropathy through Genetic Studies of IgA1 Glycosylation

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $665,167

## Abstract

Summary
IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and is the most
frequent cause of kidney failure in Asians, and the leading cause of glomerulonephritis in Caucasian
populations; however, this disease is uncommon in African populations. Kidney biopsies are required for the
diagnosis and are characterized by immunodeposits of IgA1 with C3 (and occasionally IgG and IgM) in the
glomerulus, which in turn damages the kidneys.
We have previously utilized state of the art approaches in genomics, biochemistry, and immunology to
understand IgAN to provide insight into IgAN pathogenesis. In this proposal we will continued to elucidate IgAN
pathogenesis, using genetics, biochemistry, immunology and animal models. We will use an exome-wide
association study to identify rare mutations in IgAN, stratified by IgA1 glycosylation defects. We will generate a
transcriptomic map of IgA-producing B-cells derived from IgAN patients to define the molecular networks in
regulating galactose deficient IgA1. Finally, using Galnt14 knockout mice we will evaluate the role of O-
glycosylation in the homing and trafficking of B-lymphocytes in response to an antigenic challenge.
Our research proposal therefore focuses of IgAN pathogenesis, genetic variants, host factors, biochemical and
immunological analysis and the interactions of these different components. At the conclusion of this project, we
will have identified novel variants using exome-wide association studies, generated a transcriptomic map and
defined networks in regulating galactose-deficient IgA1, and the role of O-glycosylation in the homing and
trafficking of B-lymphocytes, elucidating new mechanisms for IgAN pathogenesis.

## Key facts

- **NIH application ID:** 10399589
- **Project number:** 5R01DK082753-11
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** ALI G GHARAVI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $665,167
- **Award type:** 5
- **Project period:** 2009-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10399589

## Citation

> US National Institutes of Health, RePORTER application 10399589, Elucidating IgA nephropathy through Genetic Studies of IgA1 Glycosylation (5R01DK082753-11). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10399589. Licensed CC0.

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