Histological grading of tertiary lymphoid structures correlates with renal impairment and adverse outcomes in ANCA-associated glomerulonephritis.

Authors

Yujia Wang, Kaiqi Huang, Jiaye Fang, Caiming Chen, Zigui Zheng, Xuan Tao, Jianxin Wan, Hong Chen, Huabin Ma, Yanfang Xu

Published in

Frontiers in immunology. Volume 17. Pages 1916074. Epub Sep 16, 2026.

Abstract

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.
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.
High-grade TLS patients exhibited significantly lower estimated glomerular filtration rate (9.3 vs. 21.4 mL/min/1.73 m², p<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<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.
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.

PMID:
42818786
Bibliographic data and abstract were imported from PubMed on 01 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.