{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:04:47Z","timestamp":1789538687364,"version":"build-2803163510"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"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>Tertiary lymphoid structures (TLS) are organized immune aggregates that develop in non-lymphoid tissues during chronic inflammation and are associated with adverse outcomes in various kidney diseases. Their role in antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis remains poorly characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single-center retrospective study included 74 patients with biopsy-confirmed ANCA-associated glomerulonephritis. Intrarenal TLS were graded from G0 to G4 and dichotomized into low-grade (G0-2, n=37) and high-grade (G3-4, n=37). Clinical, laboratory, histopathological, and immunohistochemical parameters, systemic inflammatory indices, and progression to end-stage renal disease (ESRD) were compared between groups. Renal survival was analyzed using Kaplan-Meier and univariate and multivariate Cox regression to identify independent factors independently associated with ESRD. A prognostic nomogram incorporating these independently associated factors was constructed and internally validated using bootstrap-resampled calibration curves and the C-index.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>High-grade TLS patients exhibited significantly lower estimated glomerular filtration rate (9.3 vs. 21.4 mL\/min\/1.73 m\u00b2, p&amp;lt;0.001), higher Birmingham Vasculitis Activity Score (17.0 vs. 14.0, p=0.016), lower complement C3, and higher C-reactive protein, as well as a greater prevalence of crescentic\/sclerotic histology (89.2% vs. 21.6%, p&amp;lt;0.001). High-grade TLS biopsies showed increased CD20+ B-cell and CD21+ follicular dendritic cell infiltration, while peripheral blood displayed a higher percentage of CD3+ T cells and an elevated Inflammation Burden Index (IBI). ESRD occurred in 51.4% of high-grade versus 27.0% of low-grade patients (p=0.032). High-grade TLS was associated with worse renal survival (log-rank p=0.021). In multivariate Cox regression, high-grade TLS, lower eGFR, lower complement C3, and sclerotic Berden class were identified as potential independent risk factors for ESRD in this cohort. A nomogram integrating these four predictors showed promising discriminative ability (C-index=0.897) and satisfactory calibration for predicting the probability of ESRD occurrence at 1 year.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>High-grade intrarenal TLS appear to be associated with more severe renal impairment, aggressive histopathology, and poor kidney survival in this ANCA-associated glomerulonephritis cohort. The finding that high-grade TLS may be independently associated with ESRD, together with the exploratory TLS-integrated nomogram, suggests a potential role for TLS grading in risk stratification. However, these preliminary findings warrant validation in larger prospective cohorts before any clinical application can be recommended.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1916074","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:31:48Z","timestamp":1789536708000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Histological grading of tertiary lymphoid structures correlates with renal impairment and adverse outcomes in ANCA-associated glomerulonephritis"],"prefix":"10.3389","volume":"17","author":[{"given":"Yujia","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, the First Affiliated Hospital, Fujian Medical University","place":["Fuzhou, Fujian, China"]},{"name":"Research Center for Metabolic Chronic Kidney Disease, the First Affiliated Hospital, Fujian Medical 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