# Natural history and validation of surrogate biomarkers and patient-reported outcomes for SJIA-LD

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2024 · $206,016

## Abstract

Project Summary / Abstract
Chronic lung disease in children with systemic juvenile idiopathic arthritis (SJIA-LD) is a life-threatening disorder
which is increasing in incidence and for which there are no proven effective treatments. SJIA-LD manifests as
interstitial lung disease (ILD) with varying degrees of pulmonary alveolar proteinosis (PAP), fibrosis, and
pulmonary artery hypertension, and frequently progresses to hypoxic respiratory failure. Although research is
urgently needed to define optimal treatments for SJIA-LD, key knowledge gaps remain that are barriers
to future research: a case definition, prospective evaluation of clinical disease progression, surrogate
biomarkers of disease activity, and LD-specific patient-reported outcomes (PROs). Our objectives are to
define SJIA-LD, its clinical disease progression, and surrogate biomarkers, to accelerate future research in this
disease. We have developed and published preliminary outcome measures, identified serum inflammatory
mediators and markers of lung injury in SJIA-LD patients, and piloted surveys to identify SJIA-LD specific
symptoms that can be measured using validated PROs. To operationalize these preliminary findings, we have
launched a pilot multicenter prospective cohort study of SJIA-LD, which to date has enrolled 45 patients through
the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. Our central hypothesis
is that this proposed SJIA-LD study will result in the ability to accurately define SJIA-LD cases and
characterize disease trajectories, and validate surrogate biomarkers of clinical disease progression and
LD-specific PROs. In this study, we will enroll ~80 SJIA-LD patients across the CARRA network, and
prospectively collect clinical data, biosamples and PROs over 2 years of follow-up. In Aim 1, we will determine
the clinical SJIA-LD characteristics and progression by collecting LD features at baseline and longitudinally, and
use this to support a data-derived expert consensus definition of SJIA-LD. In Aim 2, we will validate biomarkers
of inflammation and lung injury in children with SJIA-LD by determining longitudinal (baseline, 6-months, and
end-of-study) levels of cytokines, chemokines and lung injury markers, their responsiveness to change, and
correlating them with clinical disease activity. In Aim 3, we will utilize PRO measures that reflect quality of life
and lung disease symptoms in children with SJIA-LD by tracking changes in existing measures captured through
the CARRA Registry, as well as in previously-validated lung disease-specific instruments which measure patient-
reported SJIA-LD symptoms. We will leverage the CARRA Registry and infrastructure to longitudinally assess
clinical disease features, surrogate biomarkers of disease activity, lung damage and PROs in a prospective
cohort of children with SJIA-LD. Successful completion of the proposed aims are necessary to accelerate future
clinical research, including interventional studi...

## Key facts

- **NIH application ID:** 10977804
- **Project number:** 1R01AR084717-01
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** YUKIKO KIMURA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $206,016
- **Award type:** 1
- **Project period:** 2024-08-15 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10977804

## Citation

> US National Institutes of Health, RePORTER application 10977804, Natural history and validation of surrogate biomarkers and patient-reported outcomes for SJIA-LD (1R01AR084717-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10977804. Licensed CC0.

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