# Antigen specificity of plasma cells in Hidradenitis suppurativa skin lesions

> **NIH NIH R21** · EMORY UNIVERSITY · 2024 · $264,227

## Abstract

Project Summary
Hidradenitis suppurativa (HS) is a chronic inflammatory dermatosis that causes recurrent scarring abscesses
and tunnels in the groin, axillae, and perineum. It affects approximately 325,000 Americans, predominantly
women and African Americans. Outside the US, 1% of people from high-income countries suffer from it. HS
causes recurrent scarring abscesses and reduced quality of life. Most patients live with constant pain, and this
leads to chronic opioid use, impaired relationships, and higher suicide risk. Patients with HS are 2-3 times more
likely to commit suicide than the general population, and this association is even stronger among women. There
is one FDA-approved cure, but it is effective only in 50% of those with moderate to severe disease. A better
understanding of HS pathogenesis is needed to develop novel treatment strategies to improve the quality of life
in those living with this devastating disease.
 Epstein Barr Virus (EBV), a ubiquitous gamma herpesvirus is associated with several autoimmune diseases
including Rheumatoid arthritis, Multiple Sclerosis (MS), and Systemic Lupus Erythematosus. A recent
longitudinal study with a large cohort provided strong evidence that EBV is a trigger for autoimmunity by
observing that EBV infection increased the risk of future MS onset by 32-fold. While the mechanisms by which
EBV may trigger autoimmunity are unclear, there is compelling evidence that chronic EBV reactivation and
molecular mimicry between EBV and human proteins are factors.
 Our preliminary data, suggests a link between EBV and HS. In preliminary studies, we compared sera from
HS patients with controls. We found that HS patients make antibodies that are reactive to (a) select epitopes in
EBV and (b) human self-antigens. Non-HS control individuals make antibodies against EBV but they do not make
antibodies against the expanded set of EBV epitopes that the HS patients do. These preliminary results suggest
a linkage between immune reactivity to novel EBV epitopes and self-antigens in HS. Interestingly, preliminary
studies show that HS skin lesions contain pauciclonal, class-switched, somatically mutated B cells and plasma
cells. The specificity of the antibodies encoded are unknown, and whether these play a crucial role in HS
pathogenesis remains unclear as well. Here we propose to (i) determine the clonal dynamics of B cells and
plasma cells in HS skin lesions (Aim 1), (ii) recreate human monoclonal antibodies encoded by these cells, and
test their ability to bind EBV and self-antigens. We will also map the unique epitopes in EBV targeted by these
HS skin lesion-derived monoclonal antibodies. We will then test if these EBV epitopes can be used as an ELISA
screening tool to assess disease severity in HS patients (Aim 2). The proposed work is significant because the
knowledge gained from these studies will help better understand the link between EBV and HS pathogenesis
and may help identify novel therapeutic strategies to...

## Key facts

- **NIH application ID:** 10988747
- **Project number:** 1R21AI186218-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** JOSHY JACOB
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $264,227
- **Award type:** 1
- **Project period:** 2024-07-17 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10988747

## Citation

> US National Institutes of Health, RePORTER application 10988747, Antigen specificity of plasma cells in Hidradenitis suppurativa skin lesions (1R21AI186218-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10988747. Licensed CC0.

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