Primary Sjögren’s syndrome (SS) is the second-most common systemic autoimmune disease.

Primary SS causes insufficient moisture production in certain glands of the body, leading to dry eyes and mouth. People with primary SS can experience complications with their lungs and kidneys. A major risk for these patients is also the development of lymphomas.

Unfortunately, there is currently no cure for this disease and the diagnosis of complicating lymphoma is usually delayed months or even years after onset, leading to poor outcomes.

Dr Jing Jing Wang has received a Flinders Foundation Health Seed Grant to address these issues by identifying potential biomarkers for earlier detection and new treatments for primary SS, in particular a blood antibody marker known as ‘rheumatoid factor’.

Rheumatoid factors are a group of autoantibodies. They are commonly found in the saliva and serum of people with primary SS and are independent predictors of lymphoma in primary SS.

Dr Wang and her team will study the molecular composition of rheumatoid factors in the blood and tissues from patients with primary Sjögren’s syndrome, who developed lymphoma, and identify molecular signatures for early diagnostic markers.

The new research will use advanced proteomic technology to profile molecular signatures of pathogenic (disease causing) rheumatoid factors in primary SS, using sophisticated instrumentation called ‘mass spectrometry’.

“In preliminary studies using mass spectrometry-based proteomic technology, we have sequenced rheumatoid factors directly from human serum and showed that pathogenic rheumatoid factor ‘clonotypic’ peptides are detectable years before the clinical presentation of life-threatening vasculitis in patients with primary SS. This indicates that these surrogate peptides may serve as early diagnostic markers,” Dr Wang said.

“Furthermore, we pioneered the use of quantitative barcode proteomics where specific protein sequences are used to ‘barcode’ the lymphoma clones to demonstrate expansion of rheumatoid factor clones during disease progression, and also their disappearance with immunosuppression treatments.

“Knowledge gained through this research will empower clinicians and directly benefit autoimmune patients with earlier diagnosis and better prediction of treatment response.”

Dr Wang believes this proteomic approach could be adapted to other autoimmune diseases (e.g. lupus and rheumatoid arthritis) and infectious diseases, such as influenza and COVID-19).

Research category: Biomedical

Project title: Molecular analysis of pathogenic rheumatoid factor repertoires in patients with primary Sjögren’s syndrome 

Lead researcher: Dr Jing Jing Wang