Differential expression of cell death-associated markers may reflect distinct renal lesion patterns in effusive and...

Feline infectious peritonitis (FIP) is a fatal, immune-mediated disease caused by the mutagenic variants of feline coronavirus and manifests as effusive (wet) and non-effusive (dry) clinical forms with distinct pathological features. Although necrosis is a common histopathological finding in FIP, the contribution of specific regulated cell death (RCD) pathway-associated protein expression patterns to tissue injury across different clinical forms remains poorly understood. This study aimed to concurrently and comparatively evaluate apoptosis, necroptosis, autophagy-associated cell death, and ferroptosis in the renal tissues of cats with effusive and non-effusive FIP.

Archival kidney samples from cats diagnosed with effusive (n = 18) and non-effusive (n = 18) FIP were included in the study. Immunohistochemistry on tissue sections was performed to assess markers associated with apoptosis by Caspase-3 and Caspase-8, necroptosis-associated signaling by RIP3, autophagy-associated activity by LC3-II, and ferroptosis-associated lipid metabolic susceptibility by ACSL-4. Necrosis was evaluated histomorphologically using a semi-quantitative scoring system, and immunohistochemical expression levels were digitally quantified and statistically compared between the groups.

Histopathological evaluation revealed widespread tubular degeneration and necrosis in both clinical forms, with no significant difference in necrosis scores between the effusive and the non-effusive FIP. In contrast, quantitative differences in RCD-associated marker expression were identified. The non-effusive form exhibited significantly higher Caspase-3, Caspase-8, and LC3-II immunoreactivity, suggesting a higher prevalence of markers associated with caspase-dependent apoptosis and autophagy-associated activity. Conversely, RIP3 and ACSL-4 immunoreactivity were significantly increased in the effusive form, indicating increased expression of markers associated with necroptosis-related and ferroptosis-related processes. All evaluated markers were detected in both disease forms, indicating overlapping expression profiles rather than mutually exclusive pathway involvement.

Collectively, these findings indicate that RCD-associated proteins are differentially expressed in the effusive and the non-effusive FIP, reflecting quantitative differences in marker expression rather than definitive evidence of pathway-specific activation. While the non-effusive form showed higher expression of markers associated with caspase-dependent apoptosis and autophagy-associated activity, the effusive form exhibited increased expression of proteins related to proinflammatory and oxidative cell death-associated pathways. These findings provide a descriptive immunohistochemical profile of cell death-associated markers in renal lesions of FIP and highlight the need for future studies using complementary molecular and protein-based approaches to further clarify their functional significance.