Increased interferon signalling in vaginal tissue of patients with primary Sjögren's syndrome.

Abstract

Vaginal dryness is an important factor influencing sexual function in women with primary Sjögren's syndrome (pSS). Previous studies showed a higher degree of inflammation in vaginal biopsies from pSS patients 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 pSS patients' vaginal tissue. Vaginal biopsies of eight premenopausal pSS patients with vaginal dryness complaints and seven 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)). The most enriched pathway in vaginal biopsies from pSS patients compared to non-pSS controls was the IFN signalling pathway (p=0.01). Pathway scores for JAK-STAT and Notch signalling were also higher (p=0.01, both pathways). Conversely, TGFβ-signalling and angiogenesis pathway scores were lower in pSS (p=0.02 and p=0.04, respectively). Differences in IFN signalling between pSS patients and non-pSS controls were confirmed by PCR and MxA tissue staining. No CD123+ pDCs were detected in vaginal biopsies. Interferon-stimulated gene expression levels correlated positively with CD45+ cell numbers in vaginal biopsies and serum anti-SSA/Ro positivity. Upregulation of IFN signalling 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 i.e. vaginal dryness.