# Kidney Tertiary Lymphoid Tissues and Poor Immunosuppressive Response in IgA Nephropathy

## TL;DR

This study finds that kidney tertiary lymphoid tissues are linked to poor response to immunosuppressive treatment in IgA nephropathy patients.

## Contribution

The study identifies TLTs as a novel predictor of immunosuppressive treatment outcomes in IgA nephropathy.

## Key findings

- 429 out of 845 IgAN patients had kidney interstitial TLTs, with 16.8% at advanced stages.
- TLTs presence and stage were strongly associated with poor immunosuppressive response.
- Combining TLTs with clinical and macrophage data improved prediction accuracy (AUC of 0.90).

## Abstract

Ectopic lymphoid structures termed as tertiary lymphoid tissues (TLTs) are observed in certain kidney diseases, including IgA nephropathy (IgAN); however, clinical relevance of TLTs remains unclear.

This prospective cohort study included 845 Chinese patients with IgAN with proteinuria ≥ 1 g/d despite 3 months of optimized supportive care with renin-angiotensin system inhibitors. Patients received immunosuppression for a median of 22 months. Kidney interstitial TLTs, defined as lymphocyte aggregates, were counted using immunochemistry and staged by the absence (stage I) or presence of follicular dendritic cells (FDCs) (stage II) or germinal centers (GCs) (stage III). The outcome was response to immunosuppression, defined as no remission with up to 12 months of immunosuppression.

Kidney interstitial TLTs were present in 429 of 845 patients with IgAN (50.8%), of whom 72 of 429 (16.8%) had TLTs at advanced stages (stage II or III). Compared with patients without TLTs, both the presence and stage of TLTs were associated with significantly increased risk of poor response to immunosuppression, with an adjusted odds ratio (95% confidence interval [CI]) of 3.07 (2.16–4.37), 2.97 (2.05–4.28), and 6.25 (3.39–11.53) in those with TLTs at any stage, stage I, and advanced stage, respectively. This grade association remained consistent across all prespecified subgroups. The stage and number of TLTs predicted poor response to immunosuppression with an area under receiver operating characteristic curve (AUC) of 0.81 (95% CI: 0.75–0.87). The AUC increased to 0.90 (95% CI: 0.87–0.94) when we combined TLTs with the clinical and glomerular macrophage data at biopsy.

The presence of interstitial TLTs at diagnosis was associated with poor response to immunosuppression in IgAN.