# Establishing the contributions of monogenic etiologies to hidradenitis suppurativa pathogenesis

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $700,744

## Abstract

Pathological inflammation is a source of substantial morbidity underlying clinically diverse diseases that are
marked by irreversible tissue damage. Hidradenitis suppurativa (HS) is a prevalent inflammatory skin disease
that shares features with these other disorders, including repeated bouts of unprovoked inflammation causing
pain, hyperplasia, aberrant healing, and fibrosis. HS is debilitating, difficult to manage, and has many unmet
medical needs. Notably, HS is in dire need of new treatments, with the lone FDA-approved drug failing to illicit a
clinical response in ~35% of patients. Human genetic studies help to identify and prioritize drug targets and
improve drug development success rates. However, relatively few human genetic studies have been performed
for HS and these have been conducted in small cohorts. Furthermore, although African Americans are at three
times the risk of HS, they have been excluded from those studies. Importantly, no GWAS or exome wide studies
have been published for HS. To date, four monogenic etiologies have been described for HS, one of which
implicates an inborn error of immunity (IEI). IEI are single-gene disorders comprising a class of nearly 500
extensively studied genes that cause improper function of the immune system, resulting in pathological
inflammation, autoimmunity, and/or increased susceptibility to infection. IEI underlie a range of phenotypes that
span multi-organ dysfunction to more focal outcomes, and some include HS and/or clinical features that overlap
with HS. There is immunological and clinical overlap between HS and IEI, and yet IEI have not been rigorously
investigated with HS genetic studies. Furthermore, IEI contribute to the genetic architecture of prevalent
multifactorial disorders and can have important clinical implications for the patients that harbor them by
presenting opportunities for targeted interventions and individualized screening. As was found to be the case for
other inflammatory diseases such as inflammatory bowel disease and atopic dermatitis, we hypothesize IEI are
important components of HS pathogenesis. Specifically, we will first test the hypothesis that some people with
an HS diagnosis have an IEI by generating exome data and performing a diagnostic analysis followed by
validation of identified mutations. Next, we will test the hypothesis that IEI pathways are a component of HS
pathogenesis. We will use burden testing with exome data and genome-wide association studies to identify
genes, pathways, and cell types that are relevant to HS and then determine the prevalence of IEI genes and
pathways in HS. Our approach is to leverage large HS cohorts with ancestral diversity that we have built with
clinical collaborators who specialize in HS treatment and industry partners running HS clinical trials. The
successful completion of these studies will help to identify subsets of HS research participants with IEI (some of
which will have immediate clinical relevance), will dete...

## Key facts

- **NIH application ID:** 11159205
- **Project number:** 7R01AR080796-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Lynn Petukhova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $700,744
- **Award type:** 7
- **Project period:** 2024-06-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11159205

## Citation

> US National Institutes of Health, RePORTER application 11159205, Establishing the contributions of monogenic etiologies to hidradenitis suppurativa pathogenesis (7R01AR080796-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11159205. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*