Developing the basis for precision medicine in primary Sjögren’s syndrome

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease mainly affecting females, with substantial morbidity and increased mortality in lymphoma.

The clinical presentation varies considerably and selecting patients and evaluating outcomes in clinical trials has proven difficult. The specific genetic influence in development of pSS sub-phenotypes is largely unknown.

We have built one of the biggest patient cohorts worldwide in which we will implement stratification of patients with pSS based on susceptibility genes, epigenetic regulation, transcription- and proteomic profiles and integrate with clinical data to predict long-term outcome.We aim to identify novel risk genes and develop a polygenic risk score for pSS and its phenotypes, including lymphma.

Further, to identify epigenetic, transcriptomic and protein biomarkers for pSS with incident lymphomas and long-term outcome.

Interferon (IFN) activation assessed by a protein IFN and DNA methylation IFN score will be correlated with clinical manifestations and lymphoma.

Using single cell transcriptomics in PBMC and purified B cells, specific cell subtypes, clonality and receptor usage will be determined in pSS and its phenotypes, to elucidate disease mechanisms.The goal is to understand disease pathogenesis and use identified biomarkers to improve patient subgroup stratification, treatment, follow up and prognosis, specifically the risk for lymphoma – to bring precision medicine to patients with Sjögren’s syndrome.