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

IF 7.2 2区医学 Q1 IMMUNOLOGY Journal of Clinical Immunology Pub Date : 2024-10-07 DOI:10.1007/s10875-024-01817-3

Astrid C van Stigt, Jan H von der Thüsen, Dana A M Mustafa, Thierry P P van den Bosch, Karishma A Lila, Disha Vadgama, Martin van Hagen, Virgil A S H Dalm, Willem A Dik, Hanna IJspeert

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Abstract

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.

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常见变异性免疫缺陷症肉芽肿的组织病理学特征与其他肉芽肿病不同

肉芽肿病会影响多达 20% 的常见变异性免疫缺陷病（CVID）患者。肉芽肿由高度活化的免疫细胞组成，是对抗原诱因的反应。然而，CVID 肉芽肿的基本病理生理学尚不清楚，具体诱因也不明确。CVID 中肉芽肿的形成常与肉样瘤病相提并论，但两者的临床背景和预后不同，这表明两者的发病机制不同。本研究旨在探讨 CVID 肉芽肿的细胞组织和蛋白质组学是否有别于其他肉芽肿疾病。因此，研究人员用苏木精和伊红对 CVID、肉芽肿病、结核病和异物诱发的假肉芽肿病患者的甲醛固定石蜡包埋活检组织切片进行染色，并评估其组织病理学特征。进行了靶向空间蛋白质分析，并使用免疫荧光多重测定法分析细胞组织。组织学分析表明，与其他肉芽肿疾病相比，CVID肉芽肿更小、周界更小、多核巨细胞更少、纤维化程度最低。空间蛋白质分析表明，所有疾病的肉芽肿都表达 CD68、CD11c、CD44、CD127 和 PD-L1。但在CVID中，纤维化相关蛋白纤连蛋白的表达减少，但CD163、CD3和FAPα在CVID肉芽肿中富集。免疫荧光分析表明，CVID 肉芽肿中的细胞组织有所不同，中性粒细胞、巨噬细胞、T 淋巴细胞和 B 淋巴细胞的涌入增多。总之，与肉芽肿病、结核病和假肉芽肿病相比，CVID 的肉芽肿显示出不同的组织学和细胞组织，髓细胞和淋巴细胞大量涌入，这表明肉芽肿的形成有其独特的发病机制。

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来源期刊

Journal of Clinical Immunology 医学-免疫学

CiteScore

12.20

自引率

9.90%

发文量

218

审稿时长

2 months

期刊介绍： The Journal of Clinical Immunology publishes impactful papers in the realm of human immunology, delving into the diagnosis, pathogenesis, prognosis, or treatment of human diseases. The journal places particular emphasis on primary immunodeficiencies and related diseases, encompassing inborn errors of immunity in a broad sense, their underlying genotypes, and diverse phenotypes. These phenotypes include infection, malignancy, allergy, auto-inflammation, and autoimmunity. We welcome a broad spectrum of studies in this domain, spanning genetic discovery, clinical description, immunologic assessment, diagnostic approaches, prognosis evaluation, and treatment interventions. Case reports are considered if they are genuinely original and accompanied by a concise review of the relevant medical literature, illustrating how the novel case study advances the field. The instructions to authors provide detailed guidance on the four categories of papers accepted by the journal.