Granulomas in Common Variable Immunodeficiency Display Different Histopathological Features Compared to Other Granulomatous Diseases.

Autor: van Stigt AC; Erasmus Medical Center, Laboratory of Medical Immunology, Department of Immunology, Dr. Molewaterplein 40, Rotterdam, 3015 GD, The Netherlands.; Department of Internal Medicine, Division of Allergy and Clinical Immunology, Erasmus Medical Center, Rotterdam, The Netherlands., von der Thüsen JH; Department of Pathology and Clinical Bioinformatics, Erasmus Medical Center, Rotterdam, The Netherlands., Mustafa DAM; Department of Pathology and Clinical Bioinformatics, Erasmus Medical Center, Rotterdam, The Netherlands.; The Tumor Immuno-Pathology Laboratory, Department of pathology, Erasmus Medical Center, Rotterdam, The Netherlands., van den Bosch TPP; Department of Pathology and Clinical Bioinformatics, Erasmus Medical Center, Rotterdam, The Netherlands., Lila KA; Department of Pathology and Clinical Bioinformatics, Erasmus Medical Center, Rotterdam, The Netherlands., Vadgama D; Department of Pathology and Clinical Bioinformatics, Erasmus Medical Center, Rotterdam, The Netherlands.; The Tumor Immuno-Pathology Laboratory, Department of pathology, Erasmus Medical Center, Rotterdam, The Netherlands.; Department of Pulmonary Medicine, Erasmus Medical Center, Rotterdam, The Netherlands., van Hagen M; Erasmus Medical Center, Laboratory of Medical Immunology, Department of Immunology, Dr. Molewaterplein 40, Rotterdam, 3015 GD, The Netherlands.; Department of Internal Medicine, Division of Allergy and Clinical Immunology, Erasmus Medical Center, Rotterdam, The Netherlands., Dalm VASH; Erasmus Medical Center, Laboratory of Medical Immunology, Department of Immunology, Dr. Molewaterplein 40, Rotterdam, 3015 GD, The Netherlands.; Department of Internal Medicine, Division of Allergy and Clinical Immunology, Erasmus Medical Center, Rotterdam, The Netherlands., Dik WA; Erasmus Medical Center, Laboratory of Medical Immunology, Department of Immunology, Dr. Molewaterplein 40, Rotterdam, 3015 GD, The Netherlands., IJspeert H; Erasmus Medical Center, Laboratory of Medical Immunology, Department of Immunology, Dr. Molewaterplein 40, Rotterdam, 3015 GD, The Netherlands. h.ijspeert@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Journal of clinical immunology [J Clin Immunol] 2024 Oct 07; Vol. 45 (1), pp. 22. Date of Electronic Publication: 2024 Oct 07.
DOI: 10.1007/s10875-024-01817-3
Abstrakt: Granulomatous disease affects up to 20% of patients with Common Variable Immunodeficiency (CVID). Granulomas are comprised of highly activated immune cells, and emerge in response to antigenic triggers. In CVID granulomas however, the underlying pathophysiology is unclear and the specific trigger remains unknown. Granuloma formation in CVID is often compared to sarcoidosis, although clinical context and prognosis differ, suggesting a different pathogenesis. The aim of this study was to investigate if the cellular organization and proteomics of granulomas in CVID is different from other granulomatous diseases. Therefore, tissue slides from formaldehyde fixed paraffin embedded biopsies obtained from patients with CVID, sarcoidosis, tuberculosis and foreign-material induced pseudo-sarcoidosis were stained with hematoxylin and eosin and assessed for histopathological characteristics. Targeted spatial protein analysis was performed, and immune fluorescent multiplex assays were used to analyze the cellular organization. Histological analysis revealed that CVID granulomas were smaller, less circumscribed, with fewer multinucleated giant cells and minimal fibrosis compared to the other granulomatous diseases. Spatial protein analysis showed that granulomas in all diseases expressed CD68, CD11c, CD44, CD127, and PD-L1. However in CVID, reduced expression of the fibrosis-related protein fibronectin, but enrichment of CD163, CD3 and FAPα inside CVID granulomas was observed. Immunofluorescence analysis conformed a different cellular organization in CVID granulomas with increased influx of neutrophils, macrophages, T and B lymphocytes. In conclusion, granulomas in CVID display a different histological and cellular organization with increased influx of myeloid and lymphoid cells, compared to sarcoidosis, tuberculosis and pseudo-sarcoidosis, indicating a distinct pathogenesis underlying granuloma formation.
(© 2024. The Author(s).)
Databáze: MEDLINE
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