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STAT expression and TFH1 cells in CVID granulomatosis and sarcoidosis: immunological and histopathological comparisons

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Abstract

Granulomatous disease is a serious complication of common variable immunodeficiency (CVID-GD) that occurs in 8–22% of these patients and can mimic sarcoidosis, with which it shares certain clinical, biological, and radiological features. However, few studies to date have compared the two pathologies immunologically and histologically. Therefore, we analyzed the immunological-histological findings for different tissue samples from ten patients with CVID-GD and compared them to those of biopsy-proven sarcoidosis. Specifically, we wanted to know whether or not the signaling abnormalities observed in sarcoidosis granulomas are also present in CVID-GD. Morphological differences were found between CVID-GD histology and classical sarcoidosis: mainly, the former’s notable lymphoid hyperplasia associated with granulomas not observed in the latter. All CVID-GD involved organs contained several follicular helper-T (TFH) cells within the granulomatosis, while those cells were inconstantly and more weakly expressed in sarcoidosis. Moreover, CVID and sarcoidosis granulomas expressed the phosphorylated-signal transducer and activator of transcription (pSTAT)1 and pSTAT3 factors, regardless of the organ studied and without any significant difference between entities. Our results suggest that the macrophage-activation mechanism in CVID resembles that of sarcoidosis, thereby suggesting that Janus kinase (JAK)-STAT–pathway blockade might be useful in currently difficult-to-treat CVID-GD.

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Funding

This study was carried out with the Internal Medicine Department’s own funds.

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Authors and Affiliations

  1. Internal Medicine Department, Hôpital Haut-Lévêque, Bordeaux University Hospital, Avenue de Magellan, 33604, Pessac, France

    Jean-François Viallard & Maëlig Lescure

  2. Clinical Immunology Department, Saint-Louis Paris Diderot University Hospital, Paris, France

    Eric Oksenhendler

  3. Centre Hospitalier Universitaire de Bordeaux, Service d’Immunologie Et Immunogénétique FHU ACRONIM, Hôpital Pellegrin, Place Amélie-Raba-Léon, Bordeaux, France

    Patrick Blanco & Jonathan Visentin

  4. Pathology Department, Hôpital du Haut-Lévêque, Bordeaux University Hospital, Avenue de Magellan, Pessac, France

    Marie Parrens

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  1. Jean-François Viallard
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Contributions

JFV, ML, and EO enrolled CVID patients in the cohort and collected clinical data. PB and JV ran the flow cytometry analyses. ML and MP conducted the histological analyses and tissue immunohistochemical labeling. ML computed the statistical analyses of the data. MP created the histological figures. JFV and MP wrote the paper.

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Correspondence to Jean-François Viallard.

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Compliance with ethical standards

CVID patients were enrolled in the ALTADIH Cohort which was approved by the Bordeaux University Institutional Review Board on December 20, 2006 (no. 2.04.2007). Each CVID patient gave informed written consent before participating in the study. Retrospective non opposition to participate to the study was obtained from each sarcoidosis patient.

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The authors declare no competing interests.

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428_2023_3684_MOESM3_ESM.jpg

Supplementary file3 (JPG 267 KB) Supplemental Figure Lymph-node biopsies: left column: CVID; right column: sarcoidosis. A–B Immunohistochemical (IHC) CD8 labeling showing CD8+ T cells in the granulomas surrounding germinal centers (hematoxylin & eosin (HE)×100). C–D IHC CD4 labeling showing CD4+ T cells in the granulomas surrounding germinal centers, which were more abundant than CD8+ T cells (HE ×100). E–F Inducible T-cell costimulator (ICOS; CD278) labeling which was located in the same area as CD4 on serial sections of T cells (HE ×100). G–H CD57 labeling was in the same area as CD4 on serial sections of T cells (HE ×100)

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Viallard, JF., Lescure, M., Oksenhendler, E. et al. STAT expression and TFH1 cells in CVID granulomatosis and sarcoidosis: immunological and histopathological comparisons. Virchows Arch 484, 481–490 (2024). https://doi.org/10.1007/s00428-023-03684-6

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