What does pericardial histology add? Clinicopathological patterns and inflammasome-associated signaling in pericarditis
Abstract
IntroductionPericarditis comprises heterogeneous inflammatory conditions whose etiology and immunopathological mechanisms are often difficult to establish. Histological examination is frequently performed at advanced disease stages, when morphological changes may reflect common inflammatory pathways rather than a specific cause. This study aimed to characterize histopathological patterns of pericarditis and investigate the involvement of the NLRP3 inflammasome and pyroptosis-associated pathways.Materials and methodsThis single-center retrospective study included 94 patients with pericarditis examined between January 2016 and May 2026. The cohort comprised 36 patients undergoing pericardial fenestration or pericardiectomy, 53 patients with pericarditis identified at autopsy, and 5 patients with post-transplant pericarditis. Histological assessment included inflammatory cell composition, lymphoid aggregates, fibrosis, calcification, vascularization, and vasculitis. In 15 patients, immunohistochemical and digital morphometric analyses assessed TMS1/ASC and NLRP3 expression, together with CD68 and CD3 infiltration.ResultsHistology provided definitive etiological information in a limited proportion of cases, mainly in neoplastic, granulomatous, and IgG4-related pericarditis. Distinct inflammatory patterns were nevertheless associated with clinical phenotypes. Pericarditis associated with systemic connective tissue diseases showed prominent active inflammation, including lymphoplasmacytic and neutrophilic infiltration and vasculitis. Idiopathic recurrent pericarditis (IRP) more frequently demonstrated lymphoid aggregates and relatively acellular fibrosis, whereas post-viral pericarditis showed predominantly low-grade inflammation. TMS1/ASC and NLRP3 expression was detected across all examined etiological groups, predominantly in macrophages and less frequently in lymphocytes, indicating activation of inflammasome-associated pathways irrespective of etiology. Quantitatively, TMS1-positive cells were significantly increased in systemic connective tissue disease-associated pericarditis and IRP compared with other etiologies, including cases of uncertain etiology (p = 0.038 and p = 0.042, respectively). NLRP3-positive cells were significantly increased only in IRP (p = 0.026).ConclusionAdvanced pericarditis demonstrates limited histological and immunohistochemical specificity for etiological diagnosis. TMS1/ASC and NLRP3 expression may occur irrespective of etiology and therefore should not be interpreted as specific etiological markers. However, quantitative differences in their expression, particularly in IRP, suggest differential activation of innate immune and pyroptosis-associated pathways. These findings support biological heterogeneity among pericarditis phenotypes and indicate that inflammasome profiling may contribute to mechanistic characterization of autoinflammatory pericardial disease.FundingThis work was supported by the Russian Science Foundation (RSF), Grant No. 25-25-00337, “Studying the Pathogenesis of Myocarditis and Pericarditis from the Perspective of Autoinflammation and Autoimmunity.”
Related
- GDF15 contributes to inflammasome-associated excessive mechanoresponses of hyperlipidemic PdL fibroblasts
- Monocyte-macrophage sensing of calciprotein particles in CKD-associated vascular calcification: lysosomal stress and inflammasome activation
- RNA-SpecFlow: RNA-Conditioned Spectral Flow for Histology Synthesis
- MorphoProt: RNA-Conditioned Integration of Multiscale Histology for Spatial Protein Inference
- Octave: Scale-resolved Evaluation of Spatial Gene Expression Prediction from Histology
BibTeX
@article{makarov2026what,
title = {{What does pericardial histology add? Clinicopathological patterns and inflammasome-associated signaling in pericarditis}},
author = {Igor Makarov and Valentina Myachikova and Taiana Makarova and Konstantin Konasov and Galina Boyko and Lubov Mitrofanova and Olga Moiseeva},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.2004094},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.2004094},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - What does pericardial histology add? Clinicopathological patterns and inflammasome-associated signaling in pericarditis
AU - Igor Makarov
AU - Valentina Myachikova
AU - Taiana Makarova
AU - Konstantin Konasov
AU - Galina Boyko
AU - Lubov Mitrofanova
AU - Olga Moiseeva
PY - 2026
DA - 2026/11/09
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.2004094
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.2004094
AB - IntroductionPericarditis comprises heterogeneous inflammatory conditions whose etiology and immunopathological mechanisms are often difficult to establish. Histological examination is frequently performed at advanced disease stages, when morphological changes may reflect common inflammatory pathways rather than a specific cause. This study aimed to characterize histopathological patterns of pericarditis and investigate the involvement of the NLRP3 inflammasome and pyroptosis-associated pathways.Materials and methodsThis single-center retrospective study included 94 patients with pericarditis examined between January 2016 and May 2026. The cohort comprised 36 patients undergoing pericardial fenestration or pericardiectomy, 53 patients with pericarditis identified at autopsy, and 5 patients with post-transplant pericarditis. Histological assessment included inflammatory cell composition, lymphoid aggregates, fibrosis, calcification, vascularization, and vasculitis. In 15 patients, immunohistochemical and digital morphometric analyses assessed TMS1/ASC and NLRP3 expression, together with CD68 and CD3 infiltration.ResultsHistology provided definitive etiological information in a limited proportion of cases, mainly in neoplastic, granulomatous, and IgG4-related pericarditis. Distinct inflammatory patterns were nevertheless associated with clinical phenotypes. Pericarditis associated with systemic connective tissue diseases showed prominent active inflammation, including lymphoplasmacytic and neutrophilic infiltration and vasculitis. Idiopathic recurrent pericarditis (IRP) more frequently demonstrated lymphoid aggregates and relatively acellular fibrosis, whereas post-viral pericarditis showed predominantly low-grade inflammation. TMS1/ASC and NLRP3 expression was detected across all examined etiological groups, predominantly in macrophages and less frequently in lymphocytes, indicating activation of inflammasome-associated pathways irrespective of etiology. Quantitatively, TMS1-positive cells were significantly increased in systemic connective tissue disease-associated pericarditis and IRP compared with other etiologies, including cases of uncertain etiology (p = 0.038 and p = 0.042, respectively). NLRP3-positive cells were significantly increased only in IRP (p = 0.026).ConclusionAdvanced pericarditis demonstrates limited histological and immunohistochemical specificity for etiological diagnosis. TMS1/ASC and NLRP3 expression may occur irrespective of etiology and therefore should not be interpreted as specific etiological markers. However, quantitative differences in their expression, particularly in IRP, suggest differential activation of innate immune and pyroptosis-associated pathways. These findings support biological heterogeneity among pericarditis phenotypes and indicate that inflammasome profiling may contribute to mechanistic characterization of autoinflammatory pericardial disease.FundingThis work was supported by the Russian Science Foundation (RSF), Grant No. 25-25-00337, “Studying the Pathogenesis of Myocarditis and Pericarditis from the Perspective of Autoinflammation and Autoimmunity.”
SN - 1664-3224
ER -