{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T02:59:04Z","timestamp":1771901944564,"version":"3.50.1"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Rheumatoid arthritis (RA) is a chronic autoimmune arthritis that predominantly affects adults, whereas juvenile idiopathic arthritis (JIA) comprises a heterogeneous group of childhood\u2212onset arthritides defined by age at onset, clinical phenotype, and immunological profile. Although RA and JIA are classified as distinct diseases, they share overlapping clinical and immunological features, and the nosological relationship between RA and some JIA subtypes remains debated. The global burden of RA and JIA in young people, and the similarities and differences in their underlying immunogenetic features, remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We utilized GBD 2021 data to describe trends in incidence, prevalence, and disability-adjusted life years for RA in individuals aged 0\u201319 years, as defined within the GBD framework, from 1990 to 2021. In parallel, we performed two\u2212sample Mendelian randomization (MR) using genome\u2212wide association study summary statistics from European\u2212ancestry cohorts to assess associations of genetically proxied levels of 731 immune\u2212cell traits, 91 circulating inflammatory proteins, and 1,400 serum metabolites with RA and JIA risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      From 1990 to 2021, global age\u2212standardized incidence and prevalence of RA in individuals aged 0\u201319 years increased, whereas disability\u2212adjusted life years declined slightly. The aggregated burden was higher in females and in high\u2212sociodemographic index regions. MR identified overlapping genetically proxied immune\u2212cell and inflammatory protein traits for RA and JIA, including CD28 on CD8\n                      <jats:sup>+<\/jats:sup>\n                      CD45RA\n                      <jats:sup>+<\/jats:sup>\n                      T cells, CD25 on memory B cells, signaling lymphocytic activation molecule, and Fms\u2212like tyrosine kinase 3 ligand, whereas higher genetically predicted levels of activated regulatory T cells and HLA\u2212DR on dendritic cells were associated with lower risk in both diseases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study highlights a rising global burden of GBD\u2212defined RA among children and adolescents and delineates shared and distinct patterns of genetically predicted immune\u2212cell, inflammatory protein, and metabolite traits associated with RA and JIA. These observations suggest that immunologically informed approaches could complement existing age- and phenotype-based classifications and help refine early recognition and risk stratification of inflammatory arthritis across the life course.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1661461","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T06:30:08Z","timestamp":1768372208000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Global burden and genetic insights of RA and JIA in ages 0\u201319 years: GBD 2021 and MR analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Pingyu","family":"An","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The Second Affiliated Hospital of Harbin Medical University","place":["Harbin, 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