# Scleroderma Renal Crisis as a Genetic Complementopathy

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2020 · $220,734

## Abstract

Abstract
Systemic sclerosis (SSc), also called scleroderma, is a rare disease characterized by fibrosis of connective
tissues. Some patients with SSc develop a complication called scleroderma renal crisis (SRC), which is
characterized by sudden onset of new high blood pressure and evidence of kidney damage. Though patients
can be treated with ACE inhibitors, there is still a high morbidity. Many individuals require kidney transplant or
dialysis. The pathology of SRC is strikingly similar to a different set of sudden onset kidney diseases called
thrombomicroangiopathies, or TMAs. TMAs often have an identified genetic cause, primarily by excessive
activation of the complement cascade. Complement activity is an enzymatic cascade that is used to fight
infections and dispose of cellular/tissue debris. In individuals with TMAs the complement system activates
inappropriately and damages the kidney. Because of the similarity to these two conditions, we propose that
SRC may actually be caused in some people by complement activation due to the presence of rare genetic
variants. We will identify rare variants associated with altered complement function in both Caucasians (Aim 1)
and African-Americans (Aim 2) that have scleroderma and either did or did not develop SRC. By comparing
only individuals with scleroderma to each other, we will increase our chances of finding genetic risk variants for
SRC only. In Aim 3, we will perform immunohistochemistory on SRC kidney biopsies to identify complement
deposition. Ultimately, if our hypothesis proves correct, it will open the door for the development of novel
clinical tests to identify individuals with scleroderma at risk of renal crisis, and we would also be able to try new
therapeutics that block excessive activation of complement.

## Key facts

- **NIH application ID:** 9876068
- **Project number:** 1R21AR076534-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** John Atkinson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $220,734
- **Award type:** 1
- **Project period:** 2020-05-06 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9876068

## Citation

> US National Institutes of Health, RePORTER application 9876068, Scleroderma Renal Crisis as a Genetic Complementopathy (1R21AR076534-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9876068. Licensed CC0.

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