Increased Interferon Signalling in Vaginal Tissue of Patients With Primary Sjögren Syndrome

Annie Visser; Jolien F van Nimwegen; Rick Wilbrink; Silvia C Liefers; Karin van der Tuuk; Marian J E Mourits; Gilles F H Diercks; Joost Bart; Bert van der Vegt; Léon C van Kempen; Hendrika Bootsma; Frans G M Kroese; Gwenny M Verstappen

doi:10.3899/jrheum.2023-1068

Increased Interferon Signalling in Vaginal Tissue of Patients With Primary Sjögren Syndrome

J Rheumatol. 2024 May 15:jrheum.2023-1068. doi: 10.3899/jrheum.2023-1068. Online ahead of print.

Affiliations

¹ A. Visser, BSc, University of Groningen, University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen, the Netherlands.
² J.F. van Nimwegen, MD, PhD, University of Groningen, University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen, the Netherlands.
³ R. Wilbrink, MD, University of Groningen, University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen, the Netherlands.
⁴ S.C. Liefers, PhD, University of Groningen, University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen, the Netherlands.
⁵ K. van der Tuuk, MD, PhD, University of Groningen, University Medical Center Groningen, Department of Obstetrics and Gynaecology, Groningen, the Netherlands.
⁶ M.J.E. Mourits, MD, PhD, University of Groningen, University Medical Center Groningen, Department of Obstetrics and Gynaecology, Groningen, the Netherlands.
⁷ G.F.H. Diercks, MD, PhD, University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands.
⁸ J. Bart, MD, PhD, University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands.
⁹ B. van der Vegt, MD, PhD, University of Groningen, University Medical Center Groningen, Department of Pathology and Medical Biology, Groningen, the Netherlands.
¹⁰ L.C. van Kempen, MD, PhD, University of Antwerp, Antwerp University Hospital, Department of Pathology, Antwerp, Belgium.
¹¹ H. Bootsma, MD, PhD, University of Groningen, University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen, the Netherlands.
¹² F.G.M. Kroese, PhD, PharmD, PhD, University of Groningen, University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen, the Netherlands.
¹³ G.M. Verstappen, PharmD, PhD, University of Groningen, University Medical Center Groningen, Department of Rheumatology and Clinical Immunology, Groningen, the Netherlands.

PMID: 38561184
DOI: 10.3899/jrheum.2023-1068

Abstract

Objective: Vaginal dryness is an important factor influencing sexual function in women with primary Sjögren syndrome (pSS). Previous studies showed a higher degree of inflammation in vaginal biopsies from patients with pSS compared to non-pSS controls. However, the molecular pathways that drive this inflammation remain unclear. Therefore, the aim of this study was to investigate inflammatory pathway activity in the vaginal tissue of patients with pSS.

Methods: Vaginal biopsies of 8 premenopausal patients with pSS experiencing vaginal dryness and 7 age-matched non-pSS controls were included. Expression of genes involved in inflammation and tissue homeostasis was measured using NanoString technology and validated using TaqMan Real-Time PCR. Vaginal tissue sections were stained by immunohistochemistry for myxovirus resistance protein 1 (MxA) and CD123 (plasmacytoid dendritic cells [pDCs]).

Results: The most enriched pathway in vaginal biopsies from patients with pSS compared to non-pSS controls was the interferon (IFN) signaling pathway (P < 0.01). Pathway scores for Janus kinase and signal transducer and activator of transcription (JAK-STAT) and Notch signaling were also higher (P < 0.01 for both pathways). Conversely, transforming growth factor-β signaling and angiogenesis pathway scores were lower in pSS (P = 0.02 and P = 0.04, respectively). Differences in IFN signaling between patients with pSS and non-pSS controls were confirmed by PCR and MxA tissue staining. No CD123+ pDCs were detected in vaginal biopsies. IFN-stimulated gene expression levels correlated positively with CD45+ cell numbers in vaginal biopsies and serum anti-SSA/Ro positivity.

Conclusion: Upregulation of IFN signaling in vaginal tissue of women with pSS, along with its association with tissue pathology, suggests that IFNs contribute to inflammation of the vaginal wall and potentially also to clinical symptomatology (ie, vaginal dryness).