Juvenile idiopathic arthritis and rheumatoid arthritis: a narrative review of age-dependent, subtype-specific immune mechanisms, biomarkers, and treatment strategies
- 1The Second Clinical Medical College of Zhejiang Chinese Medical University
- 2State Key Clinical Specialty of Rheumatology, Department of Rheumatology, the Second Affiliated Hospital of Zhejiang Chinese Medical University
Abstract
Background: Juvenile idiopathic arthritis (JIA) and adult rheumatoid arthritis (RA) share chronic inflammatory arthritis, but their biological drivers and implications vary by developmental stage and phenotype. JIA arises during immune and skeletal maturation and encompasses heterogeneous conditions, whereas adult RA develops after skeletal maturity. Existing reviews have considered the diseases separately or focused on polyarticular JIA, leaving uncertain which adult RA-derived mechanisms, biomarkers, and treatment principles transfer to JIA phenotypes.
Main body: A targeted search of PubMed/MEDLINE and Web of Science through 25 September 2026 informed an age-by-endotype framework comparing JIA phenotypes with adult RA across immune and tissue mechanisms, structural consequences, biomarker function and evidence maturity, and treatment mechanism, exposure, and safety. Systemic JIA, conceptualized within the Still’s disease spectrum, diverges most from adult RA because of myeloid-cell activation, macrophage activation syndrome risk, and inflammation associated with interleukin-1, interleukin-6, and interleukin-18. Rheumatoid factor (RF)-positive polyarticular JIA shows partial convergence with adult seropositive RA through autoantibody-associated adaptive immunity, chronic synovitis, and erosive potential, but development and pediatric safety preclude equivalence. Oligoarticular JIA is distinguished by synovitis and uveitis, whereas enthesitis-related arthritis and juvenile psoriatic arthritis align more closely with entheseal and psoriatic-spectrum biology than with RA. Biomarker interpretation and treatment are phenotype-specific: ferritin, interleukin-18, and S100 proteins inform systemic hyperinflammation; RF and anti-citrullinated protein antibodies characterize RA-like polyarthritis; antinuclear antibodies inform uveitis surveillance; and human leukocyte antigen B27 supports classification in enthesitis-related arthritis. Treatment ranges from early interleukin-1 or interleukin-6 inhibition in systemic JIA to methotrexate, biologic disease-modifying antirheumatic drugs, and selected Janus kinase inhibitor use in RA-like polyarthritis after consideration of regulatory approval and individualized risk, and therapy directed at tumor necrosis factor or interleukin-17 in entheseal or psoriatic disease. Tissue, imaging, multi-omic, microbiome, and treatment-response biomarkers remain investigational.
Conclusions: The relationship between JIA and adult RA is phenotype- and domain-specific rather than universal. This framework identifies where adult-derived evidence can inform pediatric interpretation and where direct pediatric validation is required. Longitudinal, subtype-defined pediatric cohorts integrating tissue, imaging, and multi-omic data are needed to support mechanism-based, developmentally appropriate care.
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BibTeX
@article{sheng2026juvenile,
title = {{Juvenile idiopathic arthritis and rheumatoid arthritis: a narrative review of age-dependent, subtype-specific immune mechanisms, biomarkers, and treatment strategies}},
author = {Wenwen Sheng and Xinyue Yang and Zhenzhe Yu and Yongqi Yang and Huihe Chen and Yang Cheng and Weijie Wang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1873473},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1873473/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Juvenile idiopathic arthritis and rheumatoid arthritis: a narrative review of age-dependent, subtype-specific immune mechanisms, biomarkers, and treatment strategies
AU - Wenwen Sheng
AU - Xinyue Yang
AU - Zhenzhe Yu
AU - Yongqi Yang
AU - Huihe Chen
AU - Yang Cheng
AU - Weijie Wang
PY - 2026
DA - 2026/10/27
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1873473
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1873473/full
AB - Background: Juvenile idiopathic arthritis (JIA) and adult rheumatoid arthritis (RA) share chronic inflammatory arthritis, but their biological drivers and implications vary by developmental stage and phenotype. JIA arises during immune and skeletal maturation and encompasses heterogeneous conditions, whereas adult RA develops after skeletal maturity. Existing reviews have considered the diseases separately or focused on polyarticular JIA, leaving uncertain which adult RA-derived mechanisms, biomarkers, and treatment principles transfer to JIA phenotypes. Main body: A targeted search of PubMed/MEDLINE and Web of Science through 25 September 2026 informed an age-by-endotype framework comparing JIA phenotypes with adult RA across immune and tissue mechanisms, structural consequences, biomarker function and evidence maturity, and treatment mechanism, exposure, and safety. Systemic JIA, conceptualized within the Still’s disease spectrum, diverges most from adult RA because of myeloid-cell activation, macrophage activation syndrome risk, and inflammation associated with interleukin-1, interleukin-6, and interleukin-18. Rheumatoid factor (RF)-positive polyarticular JIA shows partial convergence with adult seropositive RA through autoantibody-associated adaptive immunity, chronic synovitis, and erosive potential, but development and pediatric safety preclude equivalence. Oligoarticular JIA is distinguished by synovitis and uveitis, whereas enthesitis-related arthritis and juvenile psoriatic arthritis align more closely with entheseal and psoriatic-spectrum biology than with RA. Biomarker interpretation and treatment are phenotype-specific: ferritin, interleukin-18, and S100 proteins inform systemic hyperinflammation; RF and anti-citrullinated protein antibodies characterize RA-like polyarthritis; antinuclear antibodies inform uveitis surveillance; and human leukocyte antigen B27 supports classification in enthesitis-related arthritis. Treatment ranges from early interleukin-1 or interleukin-6 inhibition in systemic JIA to methotrexate, biologic disease-modifying antirheumatic drugs, and selected Janus kinase inhibitor use in RA-like polyarthritis after consideration of regulatory approval and individualized risk, and therapy directed at tumor necrosis factor or interleukin-17 in entheseal or psoriatic disease. Tissue, imaging, multi-omic, microbiome, and treatment-response biomarkers remain investigational. Conclusions: The relationship between JIA and adult RA is phenotype- and domain-specific rather than universal. This framework identifies where adult-derived evidence can inform pediatric interpretation and where direct pediatric validation is required. Longitudinal, subtype-defined pediatric cohorts integrating tissue, imaging, and multi-omic data are needed to support mechanism-based, developmentally appropriate care.
SN - 1664-3224
ER -