# Autoantibody mediated pathogenesis in chronic rhinosinusitis with nasal polyps: mechanisms and consequences

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $395,000

## Abstract

Project Summary
B-cells and antibodies are a critical interface between the innate and adaptive immune systems since they
have both natural and acquired recognition of microbial antigens. However, the antibodies that naturally bind
microbial antigens frequently also react with self-antigens and, in health, these autoreactive B-cells have to be
stringently regulated to prevent autoimmunity. Recent evidence from our laboratory has previously
demonstrated that B-cells, plasmablasts and self-reactive autoantibodies against DNA and the basement
membrane are strikingly elevated in nasal polyp tissue especially in patients with severe disease. Furthermore,
we find that highly specific markers for antibody-mediated complement activation like C4d and C1rs-inh are
found at high levels within nasal polyp tissue suggesting these antibodies are activating potent pro-
inflammatory immune cascades. Our central hypotheses for the proposed work are: 1) that the these
autoantibodies are cross-reactive with natural antibodies that bind microbial antigens, 2) that the levels of
autoreactive antibodies may predict nasal polyp recurrence and 3) that the autoreactive B-cells in nasal polyps
may represent a pathogenic manifestation of a subtype of B-cells called B-1 cells that have been well
characterized in mice but remain enigmatic in humans. In the highly translational research proposed, we will
leverage the Principal Investigator’s expertise as a surgeon-scientist whose clinical interests focus on CRS
patients with his research interests in mucosal immunity. Specific aims in the experiments will: (1) identify the
specific tissue antigens that are recognized by nasal polyp derived antibodies and evaluate their potential to
cross-react with microbial proteins and activate complement; (2) comprehensively analyze samples collected
from a prospective observational trial of nasal polyp recurrence after sinus surgery for autoantibodies and
complement. Survival analysis will then be used to evaluate the biomarkers that provide significant prognostic
information; and (3) isolate the cells producing autoantibodies to identify lineage markers, conduct analysis of
antibody structural diversity and generate monoclonal autoantibodies from these cells for future studies. If
successful, these studies will firmly establish a novel pathogenic mechanism in a debilitating upper airway
disease, validate novel biomarkers of prognostic value, and discover fundamental features of human mucosal
B-cells.

## Key facts

- **NIH application ID:** 10148632
- **Project number:** 5R01AI134952-04
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Bruce K Tan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $395,000
- **Award type:** 5
- **Project period:** 2018-05-25 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10148632

## Citation

> US National Institutes of Health, RePORTER application 10148632, Autoantibody mediated pathogenesis in chronic rhinosinusitis with nasal polyps: mechanisms and consequences (5R01AI134952-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10148632. Licensed CC0.

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