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Title:Identification of critical transcriptomic signaling pathways in patients with H syndrome and Rosai-Dorfman disease
Authors:ID Lara-Reyna, Samuel (Author)
ID Poulter, James A. (Author)
ID Vasconcelos, Elton J.R. (Author)
ID Kačar, Mark, Klinika Golnik (Author)
ID McDermott, Michael F. (Author)
ID Tooze, Reuben (Author)
ID Doffinger, Rainer (Author)
ID Savic, Sinisa (Author)
Files:.pdf PDF - Presentation file, download (7,43 MB)
MD5: E580FDAD89C73040847595FF423EDCF3
Typology:1.01 - Original Scientific Article
Organization:Logo UKPBAG - University Clinic of Respiratory and Allergic Diseases Golnik
Abstract:Biallelic mutations in SLC29A3 cause histiocytosis-lymphadenopathy plus syndrome, also known as H syndrome (HS). HS is a complex disorder, with ~ 25% of patients developing autoinflammatory complications consisting of unexplained fevers, persistently elevated inflammatory markers, and unusual lymphadenopathies, with infiltrating CD68+, S100+, and CD1a[minus] histiocytes, resembling the immunophenotype found in Rosai-Dorfman disease (RDD). We investigated the transcriptomic profiles of monocytes, non-activated (M0), classically activated (M1), and alternatively activated macrophages (M2) in two patients with HS, one without autoinflammatory (HS1) and one with autoinflammatory complications (HS2). RNA sequencing revealed a dysregulated transcriptomic profile in both HS patients compared to healthy controls (HC). HS2, when compared to HS1, had several differentially expressed genes, including genes associated with lymphocytic-histiocytic predominance (e.g. NINL) and chronic immune activation (e.g. B2M). The transcriptomic and cytokine profiles of HS patients were comparable to patients with SAID with high levels of TNF. SERPINA1 gene expression was found to be upregulated in all patients studied. Moreover, higher levels of IFN[gamma] were found in the serum of both HS patients when compared to HC. Gene ontology (GO) enrichment analysis of the DEGs in HS patients revealed the terms "type I IFN," "IFN[gamma] signaling pathway," and "immune responses" as the top 3 most significant terms for monocytes. Gene expression analysis of lymph node biopsies from sporadic and H syndrome-associated RDD suggests common underlying pathological process. In conclusion, monocytes and macrophages from both HS patients showed transcriptomic profiles similar to SAIDs and also uniquely upregulated IFN[gamma] signature. These findings may help find better therapeutic options for this rare disorder.
Keywords:interferon-gamma, H syndrome, systemic autoinflammatory disease
Publication status:Published
Publication version:Version of Record
Place of publishing:Nizozemska
Publisher:Springer Nature
Year of publishing:2021
Number of pages:str. 441-457
Numbering:Vol. 41, iss. 2
PID:20.500.12556/DiRROS-13870 New window
ISSN on article:1573-2592
DOI:10.1007/s10875-020-00932-1 New window
COBISS.SI-ID:57920771 New window
Copyright:© 2020, The Author(s)
Note:Nasl. z nasl. zaslona; Soavtor iz Slovenije: Mark Kačar; Opis vira z dne 31. 3. 2021;
Publication date in DiRROS:08.04.2021
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Record is a part of a journal

Title:Journal of clinical immunology
Shortened title:J. clin. immunol.
COBISS.SI-ID:513180441 New window


License:CC BY 4.0, Creative Commons Attribution 4.0 International
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:07.12.2020

Secondary language

Keywords:interferon gama, sindrom H, sistemska avtovnetna bolezen