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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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/3/535 |
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| author | Annabelle Small Suzanne Cole Jing J. Wang Sunil Nagpal Ling-Yang Hao Mihir D. Wechalekar |
| author_facet | Annabelle Small Suzanne Cole Jing J. Wang Sunil Nagpal Ling-Yang Hao Mihir D. Wechalekar |
| author_sort | Annabelle Small |
| collection | DOAJ |
| 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 <i>n</i> = 10 patients with SjS and <i>n</i> = 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. |
| first_indexed | 2024-03-09T23:41:36Z |
| format | Article |
| id | doaj.art-27def70639894b7e969f5a412e2f8886 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-09T23:41:36Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-27def70639894b7e969f5a412e2f88862023-11-23T16:49:59ZengMDPI AGJournal of Clinical Medicine2077-03832022-01-0111353510.3390/jcm11030535Attenuation of the BTLA/HVEM Regulatory Network in the Circulation in Primary Sjögren’s SyndromeAnnabelle Small0Suzanne Cole1Jing J. Wang2Sunil Nagpal3Ling-Yang Hao4Mihir D. Wechalekar5College of Medicine and Public Health, Flinders University, Adelaide, SA 5042, AustraliaDiscovery Immunology, Janssen R&D, 1400 McKean Road, Spring House, PA 19477, USACollege of Medicine and Public Health, Flinders University, Adelaide, SA 5042, AustraliaImmunology Research Unit, GSK, 1250 S Collegeville Road, Collegeville, PA 19426, USADiscovery Immunology, Janssen R&D, 1400 McKean Road, Spring House, PA 19477, USACollege of Medicine and Public Health, Flinders University, Adelaide, SA 5042, AustraliaPrimary 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 <i>n</i> = 10 patients with SjS and <i>n</i> = 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.https://www.mdpi.com/2077-0383/11/3/535Sjögren’s syndromeBTLAHVEMco-stimulation |
| spellingShingle | Annabelle Small Suzanne Cole Jing J. Wang Sunil Nagpal Ling-Yang Hao Mihir D. Wechalekar Attenuation of the BTLA/HVEM Regulatory Network in the Circulation in Primary Sjögren’s Syndrome Journal of Clinical Medicine Sjögren’s syndrome BTLA HVEM co-stimulation |
| 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 sjogren s syndrome |
| topic | Sjögren’s syndrome BTLA HVEM co-stimulation |
| url | https://www.mdpi.com/2077-0383/11/3/535 |
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