Genes deregulated in giant cell arteritis by Nanostring nCounter gene expression profiling in temporal artery biopsies

Objective To identify differentially expressed genes in temporal artery biopsies (TABs) from patients with giant cell arteritis (GCA) with different histological patterns of inflammation: transmural inflammation (TMI) and inflammation limited to adventitia (ILA), compared with normal TABs from patie...

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Main Authors: Francesco Muratore, Carlo Salvarani, Luca Cimino, Luigi Boiardi, Nicolò Pipitone, Stefania Croci, Alessandro Zerbini, Alberto Cavazza, Alessandra Bisagni, Alessandro Rossi, Maria Nicastro, Ilaria Ferrigno, Martina Bonacini, Angelo Ghidini, Giuseppe Malchiodi
Format: Article
Language:English
Published: BMJ Publishing Group 2024-09-01
Series:RMD Open
Online Access:https://rmdopen.bmj.com/content/10/3/e004600.full
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author Francesco Muratore
Carlo Salvarani
Luca Cimino
Luigi Boiardi
Nicolò Pipitone
Stefania Croci
Alessandro Zerbini
Alberto Cavazza
Alessandra Bisagni
Alessandro Rossi
Maria Nicastro
Ilaria Ferrigno
Martina Bonacini
Angelo Ghidini
Giuseppe Malchiodi
author_facet Francesco Muratore
Carlo Salvarani
Luca Cimino
Luigi Boiardi
Nicolò Pipitone
Stefania Croci
Alessandro Zerbini
Alberto Cavazza
Alessandra Bisagni
Alessandro Rossi
Maria Nicastro
Ilaria Ferrigno
Martina Bonacini
Angelo Ghidini
Giuseppe Malchiodi
author_sort Francesco Muratore
collection DOAJ
description Objective To identify differentially expressed genes in temporal artery biopsies (TABs) from patients with giant cell arteritis (GCA) with different histological patterns of inflammation: transmural inflammation (TMI) and inflammation limited to adventitia (ILA), compared with normal TABs from patients without GCA.Methods Expression of 770 immune-related genes was profiled with the NanoString nCounter PanCancer Immune Profiling Panel on formalin-fixed paraffin-embedded TABs from 42 GCA patients with TMI, 7 GCA patients with ILA and 7 non-GCA controls.Results Unsupervised clustering of the samples revealed two distinct groups: normal TABs and TABs with ILA in one group, 41/42 TABs with TMI in the other one. TABs with TMI showed 31 downregulated and 256 upregulated genes compared with normal TABs; they displayed 26 downregulated and 187 upregulated genes compared with TABs with ILA (>2.0 fold changes and adjusted p values <0.05). Gene expression in TABs with ILA resembled normal TABs although 38 genes exhibited >2.0 fold changes, but these changes lost statistical significance after Benjamini-Yekutieli correction. Genes encoding TNF superfamily members, immune checkpoints, chemokine and chemokine receptors, toll-like receptors, complement molecules, Fc receptors for IgG antibodies, signalling lymphocytic activation molecules, JAK3, STAT1 and STAT4 resulted upregulated in TMI.Conclusions TABs with TMI had a distinct transcriptome compared with normal TABs and TABs with ILA. The few genes potentially deregulated in ILA were also deregulated in TMI. Gene profiling allowed to deepen the knowledge of GCA pathogenesis.
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spelling doaj-art-6f26fffd2bca4abc9b6b5e0ae0e8465a2025-08-20T01:55:41ZengBMJ Publishing GroupRMD Open2056-59332024-09-0110310.1136/rmdopen-2024-004600Genes deregulated in giant cell arteritis by Nanostring nCounter gene expression profiling in temporal artery biopsiesFrancesco Muratore0Carlo Salvarani1Luca Cimino2Luigi Boiardi3Nicolò Pipitone4Stefania Croci5Alessandro Zerbini6Alberto Cavazza7Alessandra Bisagni8Alessandro Rossi9Maria Nicastro10Ilaria Ferrigno11Martina Bonacini12Angelo Ghidini13Giuseppe Malchiodi14Università degli Studi di Modena e Reggio Emilia, Modena, ItalySurgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, ItalyUnit of Ocular Immunology, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Rheumatology, Azienda USL - IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Rheumatology, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, ItalyClinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL - IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, Italy10 Unit of Pathology, Azienda Unità Sanitaria Locale-IRCCS, Reggio Emilia, ItalyUnit of Pathology, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, ItalyClinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, ItalyClinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL - IRCCS di Reggio Emilia, Reggio Emilia, ItalyUnit of Otolaryngology, Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia, Reggio Emilia, ItalyVascular Surgery Unit, Azienda USL - IRCCS di Reggio Emilia, Reggio Emilia, ItalyObjective To identify differentially expressed genes in temporal artery biopsies (TABs) from patients with giant cell arteritis (GCA) with different histological patterns of inflammation: transmural inflammation (TMI) and inflammation limited to adventitia (ILA), compared with normal TABs from patients without GCA.Methods Expression of 770 immune-related genes was profiled with the NanoString nCounter PanCancer Immune Profiling Panel on formalin-fixed paraffin-embedded TABs from 42 GCA patients with TMI, 7 GCA patients with ILA and 7 non-GCA controls.Results Unsupervised clustering of the samples revealed two distinct groups: normal TABs and TABs with ILA in one group, 41/42 TABs with TMI in the other one. TABs with TMI showed 31 downregulated and 256 upregulated genes compared with normal TABs; they displayed 26 downregulated and 187 upregulated genes compared with TABs with ILA (>2.0 fold changes and adjusted p values <0.05). Gene expression in TABs with ILA resembled normal TABs although 38 genes exhibited >2.0 fold changes, but these changes lost statistical significance after Benjamini-Yekutieli correction. Genes encoding TNF superfamily members, immune checkpoints, chemokine and chemokine receptors, toll-like receptors, complement molecules, Fc receptors for IgG antibodies, signalling lymphocytic activation molecules, JAK3, STAT1 and STAT4 resulted upregulated in TMI.Conclusions TABs with TMI had a distinct transcriptome compared with normal TABs and TABs with ILA. The few genes potentially deregulated in ILA were also deregulated in TMI. Gene profiling allowed to deepen the knowledge of GCA pathogenesis.https://rmdopen.bmj.com/content/10/3/e004600.full
spellingShingle Francesco Muratore
Carlo Salvarani
Luca Cimino
Luigi Boiardi
Nicolò Pipitone
Stefania Croci
Alessandro Zerbini
Alberto Cavazza
Alessandra Bisagni
Alessandro Rossi
Maria Nicastro
Ilaria Ferrigno
Martina Bonacini
Angelo Ghidini
Giuseppe Malchiodi
Genes deregulated in giant cell arteritis by Nanostring nCounter gene expression profiling in temporal artery biopsies
RMD Open
title Genes deregulated in giant cell arteritis by Nanostring nCounter gene expression profiling in temporal artery biopsies
title_full Genes deregulated in giant cell arteritis by Nanostring nCounter gene expression profiling in temporal artery biopsies
title_fullStr Genes deregulated in giant cell arteritis by Nanostring nCounter gene expression profiling in temporal artery biopsies
title_full_unstemmed Genes deregulated in giant cell arteritis by Nanostring nCounter gene expression profiling in temporal artery biopsies
title_short Genes deregulated in giant cell arteritis by Nanostring nCounter gene expression profiling in temporal artery biopsies
title_sort genes deregulated in giant cell arteritis by nanostring ncounter gene expression profiling in temporal artery biopsies
url https://rmdopen.bmj.com/content/10/3/e004600.full
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