Kidney international reports · 2026
Immune Profiling Identifies High-Risk Neutrophil-Rich Subtype in Checkpoint Inhibitor Nephritis.
СтатьяНазвание и аннотация: Перевод в очереди
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Boudhabhay Idris, Lazareth Helene, Oniszczuk Julie, Burki Mathilde, Aubert Olivier, Redissi Alaeddine, Sakhi Hamza, Ferriere Elsa, Fabre Elizabeth, Lucibello Francesca, Girard Nicolas, Grunenwald Anne, Hamidi Houcine, Fleury Emma, Dragon-Durey Marie Agnes, Runyo Florence, Cohen Camille, Chhun Stephanie, Veyrenche Nicolas, Jamet Anne, Fourgeaud Jacques, Regnault Béatrice, Pérot Philippe, Meuleman Marie-Sophie, Mayinga Celine, Karras Alexandre, Duong Van Huyen Jean-Paul, Rabant Marion, Roumenina Lubka T, Isnard Pierre
Аннотация
INTRODUCTION: Immune checkpoint inhibitor (ICI)-induced acute interstitial nephritis (AIN) (ICI-AIN) is the leading cause of ICI-associated acute kidney injury (AKI). ICI-AIN is characterized by mononuclear immune infiltrates, although the mechanisms behind their toxicity remain unclear. We aimed to characterize these infiltrates in kidney biopsies and assess their correlation with clinical outcomes and therapeutic responses.
METHODS: We retrospectively analyzed 49 biopsy-proven ICI-AIN cases using multiplex immunofluorescence to quantify immune cells (macrophages, neutrophils, B cells, T cells, and plasmocytes). Unsupervised clustering was used to identify patient groups, which we then correlated with clinical presentation and outcomes. Finally, we explored the role of C5a/C5aR1 in neutrophil recruitment.
RESULTS: Unsupervised clustering revealed 3 immune phenotypes as follows: (i) low mononuclear (cluster 1), (ii) high mononuclear (cluster 2), and (iii) neutrophil-rich (cluster 3). Cluster 3 was associated with higher systemic inflammation (C-reactive protein: 84 vs. 15-24 mg/l, P = 0.0002; neutrophil-to-lymphocyte ratio (NLR): 7 vs. 3.2-2.3, P < 0.0001) and more severe initial AKI (peak creatinine: 360 vs. 215-208 μmol/l, P = 0.0001). Histologically, it was marked by granular casts and neutrophilic tubulitis (P < 0.0001). Despite the pyelonephritis-like appearance, urine cultures and metatranscriptomic analysis both ruled out infection. At 12 months, renal response rates to steroids were 93% (cluster 2), 67% (cluster 1), and 38% (cluster 3) (P = 0.004). Relapses occurred more frequently in cluster 3 (38% vs. 11% in cluster 1, 0% in cluster 2, P = 0.01). Urine C5a correlated with C5aR1+ neutrophil infiltration (rho = 0.78).
CONCLUSION: Our findings identify distinct ICI-AIN subtypes, with a neutrophil-rich cluster linked to complement activation and poor prognosis, offering insights into refining diagnosis and treatment strategies.
METHODS: We retrospectively analyzed 49 biopsy-proven ICI-AIN cases using multiplex immunofluorescence to quantify immune cells (macrophages, neutrophils, B cells, T cells, and plasmocytes). Unsupervised clustering was used to identify patient groups, which we then correlated with clinical presentation and outcomes. Finally, we explored the role of C5a/C5aR1 in neutrophil recruitment.
RESULTS: Unsupervised clustering revealed 3 immune phenotypes as follows: (i) low mononuclear (cluster 1), (ii) high mononuclear (cluster 2), and (iii) neutrophil-rich (cluster 3). Cluster 3 was associated with higher systemic inflammation (C-reactive protein: 84 vs. 15-24 mg/l, P = 0.0002; neutrophil-to-lymphocyte ratio (NLR): 7 vs. 3.2-2.3, P < 0.0001) and more severe initial AKI (peak creatinine: 360 vs. 215-208 μmol/l, P = 0.0001). Histologically, it was marked by granular casts and neutrophilic tubulitis (P < 0.0001). Despite the pyelonephritis-like appearance, urine cultures and metatranscriptomic analysis both ruled out infection. At 12 months, renal response rates to steroids were 93% (cluster 2), 67% (cluster 1), and 38% (cluster 3) (P = 0.004). Relapses occurred more frequently in cluster 3 (38% vs. 11% in cluster 1, 0% in cluster 2, P = 0.01). Urine C5a correlated with C5aR1+ neutrophil infiltration (rho = 0.78).
CONCLUSION: Our findings identify distinct ICI-AIN subtypes, with a neutrophil-rich cluster linked to complement activation and poor prognosis, offering insights into refining diagnosis and treatment strategies.