Abstract: FR-OR057
Phenotypic and Molecular Signatures in Acute Interstitial Nephritis
Session Information
- Pathology: Novel Mechanisms and Modalities
November 07, 2025 | Location: Room 371A, Convention Center
Abstract Time: 04:50 PM - 05:00 PM
Category: Pathology and Lab Medicine
- 1800 Pathology and Lab Medicine
Authors
- Tortonese, Sarah, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France
- Isnard, Pierre, INSERM, Paris, Île-de-France, France
- Anglicheau, Dany, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France
- Lebraud, Emilie, INSERM, Paris, Île-de-France, France
- Rabant, Marion, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France
Background
Acute interstitial nephritis (AIN) is defined by the presence of an inflammatory infiltrate in the renal interstitium and can be associated with different causes. Each one of these causes presents with suggestive but non-specific clinical, biological and histological findings, making it difficult to establish a definitive etiological diagnosis.
We hypothesized that each AIN etiology could be defined by a specific phenotypic and molecular signature.
Methods
We used a 14-plex immunofluorescence panel (IFm) to phenotype the inflammatory infiltrate on FFPE tissue and sequenced RNA from frozen tissue of the same 20 renal biopsies characteristic of 4 distinct etiologies (sarcoidosis, TINU syndrome, immuno-allergic, infectious) and normal renal biopsies.
Results
IFm results showed a specific organization and composition of the infiltrate for each one of these etiologies. Infectious AIN had a higher proportion of neutrophils (12.9%) and CD4+ T lymphocytes (27.7%) whereas immuno-allergic AIN had a higher proportion of plasma cells (10.5%) compared with the other etiologies. TINU syndrome AIN had an M2 macrophages enriched infiltrate (23.2%) while sarcoidosis AIN has an M1 macrophages enriched infiltrate (21.3%), that also contains a high proportion of regulatory T lymphocytes (18.4%). From a molecular point of view, unsupervised clustering analysis of mRNAs allowed a correct clustering of biopsies from each etiology. Analysis of the molecular pathways involved in sarcoidosis AIN compared with normal biopsies using the ORA (Overrepresentation Analysis) method showed the involvement of interferon gamma and TNF alpha-dependent pathways, consistent with previous publications.
Conclusion
In conclusion, deep phenotyping of inflammatory infiltrates and molecular study of AIN biopsies of 4 etiologies highlight specific features of each AIN etiology.
Funding
- Government Support – Non-U.S.