B-Cell Activation Biomarkers in Salivary Glands Are Related to Lymphomagenesis in Primary Sjögren’s Disease: A Pilot Monocentric Exploratory Study

Primary Sjögren’s disease is primarily driven by B-cell activation and is associated with a high risk of developing non-Hodgkin’s lymphoma (NHL). Over the last few decades, microRNA-155 (miR-155) has arisen as a key regulator of B-cells. Nevertheless, its role in primary Sjögren’s disease remains el...

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Main Authors: Dario Bruno, Barbara Tolusso, Gianmarco Lugli, Clara Di Mario, Luca Petricca, Simone Perniola, Laura Bui, Roberta Benvenuto, Gianfranco Ferraccioli, Stefano Alivernini, Elisa Gremese
Format: Article
Language:English
Published: MDPI AG 2024-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/25/6/3259
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author Dario Bruno
Barbara Tolusso
Gianmarco Lugli
Clara Di Mario
Luca Petricca
Simone Perniola
Laura Bui
Roberta Benvenuto
Gianfranco Ferraccioli
Stefano Alivernini
Elisa Gremese
author_facet Dario Bruno
Barbara Tolusso
Gianmarco Lugli
Clara Di Mario
Luca Petricca
Simone Perniola
Laura Bui
Roberta Benvenuto
Gianfranco Ferraccioli
Stefano Alivernini
Elisa Gremese
author_sort Dario Bruno
collection DOAJ
description Primary Sjögren’s disease is primarily driven by B-cell activation and is associated with a high risk of developing non-Hodgkin’s lymphoma (NHL). Over the last few decades, microRNA-155 (miR-155) has arisen as a key regulator of B-cells. Nevertheless, its role in primary Sjögren’s disease remains elusive. Thus, the purpose of this study was (i) to explore miR-155, B-cell activating factor (BAFF)-receptor (BAFF-R), and Interleukin 6 receptor (IL-6R) expression in the labial salivary glands (LSG) of patients with primary Sjögren’s disease, aiming to identify potential B-cell activation biomarkers related to NHL development. Twenty-four patients with primary Sjögren’s disease, and with available tissue blocks from a LSG biopsy performed at diagnosis, were enrolled. Among them, five patients developed B-cell NHL during follow-up (7.3 ± 3.1 years). A comparison group of 20 individuals with sicca disease was included. Clinical and laboratory parameters were recorded and the LSG biopsies were evaluated to assess local inflammation in terms of miR-155/BAFF-R and IL-6R expression. Stratifying the primary Sjögren’s disease cohort according to lymphomagenesis, miR-155 was upregulated in primary Sjögren’s disease patients who experienced NHL, more so than those who did not experience NHL. Moreover, miR-155 expression correlated with the focus score (FS), as well as BAFF-R and IL-6R expression, which were increased in primary Sjögren’s disease patients and in turn related to neoplastic evolution. In conclusion, epigenetic modulation may play a crucial role in the aberrant activation of B-cells in primary Sjögren’s disease, profoundly impacting the risk of NHL development.
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spelling doaj.art-3318819503d74c07bd9baaba219a55a52024-03-27T13:45:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01256325910.3390/ijms25063259B-Cell Activation Biomarkers in Salivary Glands Are Related to Lymphomagenesis in Primary Sjögren’s Disease: A Pilot Monocentric Exploratory StudyDario Bruno0Barbara Tolusso1Gianmarco Lugli2Clara Di Mario3Luca Petricca4Simone Perniola5Laura Bui6Roberta Benvenuto7Gianfranco Ferraccioli8Stefano Alivernini9Elisa Gremese10Clinical Immunology Unit, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, ItalyImmunology Core Facility, Gemelli Science and Technology Park, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, ItalyRare Disease Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, ItalyImmunology Core Facility, Gemelli Science and Technology Park, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, ItalyRheumatology Division, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, ItalyClinical Immunology Unit, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, ItalyInstitute of Pathology, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, ItalyInstitute of Pathology, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, ItalyDepartment of Internal Medicine, Catholic University of the Sacred Heart, 00168 Rome, ItalyImmunology Core Facility, Gemelli Science and Technology Park, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, ItalyClinical Immunology Unit, Fondazione Policlinico Universitario A. Gemelli-IRCCS, 00168 Rome, ItalyPrimary Sjögren’s disease is primarily driven by B-cell activation and is associated with a high risk of developing non-Hodgkin’s lymphoma (NHL). Over the last few decades, microRNA-155 (miR-155) has arisen as a key regulator of B-cells. Nevertheless, its role in primary Sjögren’s disease remains elusive. Thus, the purpose of this study was (i) to explore miR-155, B-cell activating factor (BAFF)-receptor (BAFF-R), and Interleukin 6 receptor (IL-6R) expression in the labial salivary glands (LSG) of patients with primary Sjögren’s disease, aiming to identify potential B-cell activation biomarkers related to NHL development. Twenty-four patients with primary Sjögren’s disease, and with available tissue blocks from a LSG biopsy performed at diagnosis, were enrolled. Among them, five patients developed B-cell NHL during follow-up (7.3 ± 3.1 years). A comparison group of 20 individuals with sicca disease was included. Clinical and laboratory parameters were recorded and the LSG biopsies were evaluated to assess local inflammation in terms of miR-155/BAFF-R and IL-6R expression. Stratifying the primary Sjögren’s disease cohort according to lymphomagenesis, miR-155 was upregulated in primary Sjögren’s disease patients who experienced NHL, more so than those who did not experience NHL. Moreover, miR-155 expression correlated with the focus score (FS), as well as BAFF-R and IL-6R expression, which were increased in primary Sjögren’s disease patients and in turn related to neoplastic evolution. In conclusion, epigenetic modulation may play a crucial role in the aberrant activation of B-cells in primary Sjögren’s disease, profoundly impacting the risk of NHL development.https://www.mdpi.com/1422-0067/25/6/3259primary Sjögren’s disease (primary Sjögren’s disease)lymphomagenesismicroRNA-155BAFF-receptorIL-6 receptorbiomarkers
spellingShingle Dario Bruno
Barbara Tolusso
Gianmarco Lugli
Clara Di Mario
Luca Petricca
Simone Perniola
Laura Bui
Roberta Benvenuto
Gianfranco Ferraccioli
Stefano Alivernini
Elisa Gremese
B-Cell Activation Biomarkers in Salivary Glands Are Related to Lymphomagenesis in Primary Sjögren’s Disease: A Pilot Monocentric Exploratory Study
International Journal of Molecular Sciences
primary Sjögren’s disease (primary Sjögren’s disease)
lymphomagenesis
microRNA-155
BAFF-receptor
IL-6 receptor
biomarkers
title B-Cell Activation Biomarkers in Salivary Glands Are Related to Lymphomagenesis in Primary Sjögren’s Disease: A Pilot Monocentric Exploratory Study
title_full B-Cell Activation Biomarkers in Salivary Glands Are Related to Lymphomagenesis in Primary Sjögren’s Disease: A Pilot Monocentric Exploratory Study
title_fullStr B-Cell Activation Biomarkers in Salivary Glands Are Related to Lymphomagenesis in Primary Sjögren’s Disease: A Pilot Monocentric Exploratory Study
title_full_unstemmed B-Cell Activation Biomarkers in Salivary Glands Are Related to Lymphomagenesis in Primary Sjögren’s Disease: A Pilot Monocentric Exploratory Study
title_short B-Cell Activation Biomarkers in Salivary Glands Are Related to Lymphomagenesis in Primary Sjögren’s Disease: A Pilot Monocentric Exploratory Study
title_sort b cell activation biomarkers in salivary glands are related to lymphomagenesis in primary sjogren s disease a pilot monocentric exploratory study
topic primary Sjögren’s disease (primary Sjögren’s disease)
lymphomagenesis
microRNA-155
BAFF-receptor
IL-6 receptor
biomarkers
url https://www.mdpi.com/1422-0067/25/6/3259
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