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Attenuation of the BTLA/HVEM Regulatory Network in the Circulation in Primary Sjögren’s Syndrome

Primary Sjögren’s syndrome (SjS) is an inflammatory autoimmune disorder which targets the lacrimal and salivary glands, resulting in glandular dysfunction. Currently, the immune drivers of SjS remain poorly understood and peripheral biomarkers of disease are lacking. The present study therefore soug...

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Autores principales: Small, Annabelle, Cole, Suzanne, Wang, Jing J., Nagpal, Sunil, Hao, Ling-Yang, Wechalekar, Mihir D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8837091/
https://www.ncbi.nlm.nih.gov/pubmed/35159987
http://dx.doi.org/10.3390/jcm11030535
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author Small, Annabelle
Cole, Suzanne
Wang, Jing J.
Nagpal, Sunil
Hao, Ling-Yang
Wechalekar, Mihir D.
author_facet Small, Annabelle
Cole, Suzanne
Wang, Jing J.
Nagpal, Sunil
Hao, Ling-Yang
Wechalekar, Mihir D.
author_sort Small, Annabelle
collection PubMed
description Primary Sjögren’s syndrome (SjS) is an inflammatory autoimmune disorder which targets the lacrimal and salivary glands, resulting in glandular dysfunction. Currently, the immune drivers of SjS remain poorly understood and peripheral biomarkers of disease are lacking. The present study therefore sought to investigate the immune cell constituents of the SjS peripheral blood, and to assess the role of the BTLA/HVEM/CD160 co-stimulatory network by characterizing expression within the periphery. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood of n = 10 patients with SjS and n = 10 age- and sex-matched healthy control donors. Cells were divided and stained with three panels of antibodies, allowing assessment of T, B, and myeloid cell subsets, and measurement of BTLA, HVEM, and CD160 surface expression by flow cytometry. We identified distinct alterations in proportions of peripheral T, B, and myeloid cell types in SjS compared with healthy controls. Expression of BTLA/CD160/HVEM and frequency of BTLA/CD160/HVEM-expressing cells were significantly altered in peripheral SjS lymphocytes. The proportion of T cells co-expressing BTLA/HVEM and CD160/HVEM were significantly reduced in SjS. We found decreased BTLA and HVEM levels on peripheral B and T cells of SjS patients, and decreased BTLA/HVEM and CD160/HVEM co-expression, demonstrating dysregulation of the BTLA/HVEM axis in the peripheral blood of SjS patients. These results indicate the potential of targeting the BTLA-HVEM axis for the treatment of SjS.
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spelling pubmed-88370912022-02-12 Attenuation of the BTLA/HVEM Regulatory Network in the Circulation in Primary Sjögren’s Syndrome Small, Annabelle Cole, Suzanne Wang, Jing J. Nagpal, Sunil Hao, Ling-Yang Wechalekar, Mihir D. J Clin Med Article Primary Sjögren’s syndrome (SjS) is an inflammatory autoimmune disorder which targets the lacrimal and salivary glands, resulting in glandular dysfunction. Currently, the immune drivers of SjS remain poorly understood and peripheral biomarkers of disease are lacking. The present study therefore sought to investigate the immune cell constituents of the SjS peripheral blood, and to assess the role of the BTLA/HVEM/CD160 co-stimulatory network by characterizing expression within the periphery. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood of n = 10 patients with SjS and n = 10 age- and sex-matched healthy control donors. Cells were divided and stained with three panels of antibodies, allowing assessment of T, B, and myeloid cell subsets, and measurement of BTLA, HVEM, and CD160 surface expression by flow cytometry. We identified distinct alterations in proportions of peripheral T, B, and myeloid cell types in SjS compared with healthy controls. Expression of BTLA/CD160/HVEM and frequency of BTLA/CD160/HVEM-expressing cells were significantly altered in peripheral SjS lymphocytes. The proportion of T cells co-expressing BTLA/HVEM and CD160/HVEM were significantly reduced in SjS. We found decreased BTLA and HVEM levels on peripheral B and T cells of SjS patients, and decreased BTLA/HVEM and CD160/HVEM co-expression, demonstrating dysregulation of the BTLA/HVEM axis in the peripheral blood of SjS patients. These results indicate the potential of targeting the BTLA-HVEM axis for the treatment of SjS. MDPI 2022-01-21 /pmc/articles/PMC8837091/ /pubmed/35159987 http://dx.doi.org/10.3390/jcm11030535 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Small, Annabelle
Cole, Suzanne
Wang, Jing J.
Nagpal, Sunil
Hao, Ling-Yang
Wechalekar, Mihir D.
Attenuation of the BTLA/HVEM Regulatory Network in the Circulation in Primary Sjögren’s Syndrome
title Attenuation of the BTLA/HVEM Regulatory Network in the Circulation in Primary Sjögren’s Syndrome
title_full Attenuation of the BTLA/HVEM Regulatory Network in the Circulation in Primary Sjögren’s Syndrome
title_fullStr Attenuation of the BTLA/HVEM Regulatory Network in the Circulation in Primary Sjögren’s Syndrome
title_full_unstemmed Attenuation of the BTLA/HVEM Regulatory Network in the Circulation in Primary Sjögren’s Syndrome
title_short Attenuation of the BTLA/HVEM Regulatory Network in the Circulation in Primary Sjögren’s Syndrome
title_sort attenuation of the btla/hvem regulatory network in the circulation in primary sjögren’s syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8837091/
https://www.ncbi.nlm.nih.gov/pubmed/35159987
http://dx.doi.org/10.3390/jcm11030535
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