Stratified medicine in primary Sjögren’s syndrome


Primary Sjögren’s syndrome (PSS) is a chronic complex immune-mediated rheumatic disease with no effective treatment to date. PSS affects 0.05-0.1% of the adults. A key barrier to therapeutic development is the marked heterogeneity in clinical manifestations and pathobiological profiles among PSS patients. We have recently described a strategy to stratify PSS patients into four subtypes with distinct clinical phenotypes and transcriptomic signatures.

Facts and figures

Project lead
W-F Ng
Newcastle University
FOREUM research grant: € 600.000

Meet the team

W-F Ng
Newcastle University
D Lendrem
Newcastle University
J-E Gottenberg
Strasbourg University
R Seror
Université Paris Sud
V Devauchelle-Pensec
Brest University
A Saraux
Brest University
S Bowman
University of Birmingham
F Barone
University of Birmingham
B Fisher
University of Birmingham
G Nordmark
Uppsala University
U Landegren
Uppsala University
R Omdal
Stavanger University Hospital
M Bombardieri
Queen Mary University London
P McMeekin


The proposal aims to further characterise the clinical significance and the underpinning pathotypes of 4 PSS subtypes. The specific objectives are:

1. To understand the natural history of the different PSS subtypes.

2. To validate the transcriptomic signatures of the PSS subtypes and re-calibrate (if necessary) for non-UK cohorts.

3. To further characterise the underpinning pathobiological profiles of the four PSS subtypes

4. To explore whether the four subtypes respond differently to treatments by reanalysing data from two clinical trials (JOQUER (hydroxychloroquine) and TRACTISS (Rituximab)

Patient voice

We formed a patient advisory board – comprising 7 patient research partners from 4 participating countries - to advise on what information to collect to best describe the burden that PSS brings to their daily lives. The health economist Dr Peter McMeekin joined us to facilitate group discussion in developing the pro-forma for data collection. We have invited 3 patient research partners to join our steering committee to provide guidance and oversight of the whole proposal.

Interim results

  • Biological differences between the four key PSS subtypes confirmed in the French and Scandinavian cohorts.
  • We have established these PSS subtypes are relatively stable over time.  
  • Transcriptional differences between the PSS subtypes confirmed. 
  • Patient advisory board established and patient-driven pro-forma for health outcome data in development. (English and French versions completed, awaiting finalization of the Norwegian and Swedish translations)
  • Historical clinical trials data reanalyzed which revealed differential responses to rituximab and hydroxychloroquine between the four substypes
  • Serum protein profiling of the subtypes ongoing
  • Preparation of collection of longitudinal outcome in progress


Tarn JR, et al. Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials. Lancet Rheumatology. 2019 Oct 1;1(2):PE85-E94.