{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:16:14Z","timestamp":1787026574190,"version":"build-2736575974"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"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>Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder caused by GGC repeat expansions in NOTCH2NLC, leading to uN2CpolyG protein deposition. Although immune-mediated renal lesions have been described in NIID, the systemic immunoinflammatory profile associated with kidney injury and its relationship with genetic burden remain undefined. This study investigated peripheral immune alterations in NIID-related nephropathy and their correlation with repeat expansion size.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter retrospective study enrolled 150 genetically and pathologically confirmed NIID patients from nine tertiary hospitals (2019-2024). Using KDIGO criteria, patients were stratified into NIID with kidney injury (NIID-KD, n=100) and NIID with no kidney injury (NIID-ND, n=50) groups. Peripheral inflammatory markers were assessed in 110 patients, and 12 T-cell-related cytokines were measured in a subset of 35 patients. Multivariable analyses adjusting for disease duration were performed. GGC repeat numbers were quantified in 48 patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After adjustment for disease duration, the NIID-KD group maintained significantly higher white blood cell counts, neutrophil counts, monocyte counts, and neutrophil-to-lymphocyte ratio compared to NIID-ND (all\n                      <jats:italic>P<\/jats:italic>\n                      &amp;lt; 0.05). Cytokine profiling revealed selectively elevated IL-6 levels in the NIID-KD group (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.042), whereas IL-17 elevation did not persist after adjustment (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.239). No significant difference in GGC repeat expansion size was observed between groups among genotyped patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NIID-associated kidney injury is characterized by a distinct immunoinflammatory signature with sustained neutrophilic and monocytic activation and IL-6 upregulation, suggesting involvement of innate immunity and IL-6-mediated inflammation in renal pathology. The absence of direct correlation between repeat expansion size and kidney involvement indicates that while genetic mutation confers disease susceptibility, acquired inflammatory mechanisms critically determine renal phenotype. These findings provide clinical evidence linking proteinopathy to innate immune activation in NIID.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1797076","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T04:21:05Z","timestamp":1776140465000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Immunological characterization of neuronal intranuclear inclusion disease with kidney injury: an exploratory analysis in a multi-center cohort"],"prefix":"10.3389","volume":"17","author":[{"given":"Ying","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Neurology, The Affiliated Hospital of Xuzhou Medical University","place":["Xuzhou, China"]},{"name":"Department of Neurology, Xuzhou Medical University","place":["Xuzhou, China"]},{"name":"Department of Neurology, Suzhou Municipal Hospital","place":["Suzhou, 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