# Longitudinal characterization of the role of the mucosal virome and microbiome in juvenile idiopathic arthritis flares

> **NIH NIH R21** · UNIVERSITY OF MINNESOTA · 2024 · $375,100

## Abstract

PROJECT SUMMARY/ABSTRACT
Juvenile idiopathic arthritis (JIA) is an autoimmune disease characterized by chronic inflammatory arthritis
affecting children. It is the most common chronic pediatric rheumatic disease. Children with JIA are typically
treated with long-term immunosuppressive medications. Although there are many good treatments available to
treat JIA, disease flares are common, affecting approximately 40% of patients even after disease control is
achieved. Yet, the etiology of disease flares has not been well-studied. Pediatric rheumatologists commonly
blame viral infection as the causes of JIA flares, and although this is a reasonable assumption, there is little
evidence to support this claim. JIA shares common pathophysiology with adult rheumatoid arthritis (RA). RA
studies have led to the mucosal origin hypothesis, which theorizes that immune responses against mucosal
organisms drives the development of autoantibodies in pre-clinical RA, prior to evidence of joint inflammation.
More recently, studies have linked viral upper respiratory infections (URIs) as a ‘second hit’ that leads to onset
of arthritis in RA. If URIs have been linked to arthritis in adults, it is highly plausible that URIs are associated with
JIA onset and flares in children, particularly since young children have far more frequent URIs compared to
adults. There is only one prospective study of viral URIs in patients with JIA, and the study found that in 20% of
patients who had disease worsening, there was a temporal association with a symptomatic infection. This
proposed study hypothesizes that children with JIA have increased susceptibility to viral URIs, prolonged viral
carriage, and prolonged dysbiosis of the nasopharyngeal microbiome following URIs. It also hypothesizes that
JIA disease flares are temporally associated with URIs, regardless of the severity of the URI symptoms. The
hypotheses will be tested by enrolling a cohort of 35 young children with JIA and 35 healthy siblings to serve as
controls. The children will undergo weekly nasal swabs for 26 weeks over the respiratory viral season
(November-April). Symptoms, hospitalizations and antibiotic use will be collected weekly using electronic
surveys. The study will also assess for incident symptomatic and asymptomatic respiratory viral infections using
an amplicon-based next-generation sequencing technique and quantify microbiome alpha and beta diversity and
composition by 16S rRNA sequencing. The study will also assess for associations between viral URI, microbiome
changes, and JIA disease activity with a self-reported JIA disease flare survey, also collected weekly.
The results of this study may provide guidance to children with JIA about risk for URIs, period of infectivity and
associations between viral infection and disease flare. Importantly, if the study identifies a relationship between
the nasopharyngeal virome and microbiome and how it affects JIA disease activity, it may lead to the
identificatio...

## Key facts

- **NIH application ID:** 11056288
- **Project number:** 1R21AR083581-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Colleen Kelly Marie Correll
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $375,100
- **Award type:** 1
- **Project period:** 2024-09-20 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11056288

## Citation

> US National Institutes of Health, RePORTER application 11056288, Longitudinal characterization of the role of the mucosal virome and microbiome in juvenile idiopathic arthritis flares (1R21AR083581-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11056288. Licensed CC0.

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