Systemic Lupus Erythematosus (SLE; «lupus») begins several years before the actual time of diagnosis, when a person has no or very mild symptoms but her/his immune cells start malfunctioning and produces antinuclear («ANAs») and other auto-antibodies (so called «preclinical lupus»). This gives an opportunity for planning preventive strategies which could potentially restore immune system function and delay (or even, prevent) lupus.
The aim of the project is to define the subgroup of individuals who are at high risk for progression into SLE. For this, we established a multi-centre inception cohort of 298 individuals with mild or non-diagnostic symptoms and positive autoantibodies (ANA [anti-nuclear antibodies]), or first-degree relatives (FDRs) of SLE patients, monitored prospectively for multiple demographics, medical, lifestyle/environmental exposures, clinical data and use of medications. After an average 18 months, 12.4% of individuals have progressed into SLE. Blood transcriptome analysis is used to define a gene signature predictive of the transition from preSLE to SLE state, and integration with the abovementioned covariates will lead to a composite ‘lupus prediction risk score’. In a complementary analysis, we are using the gene signatures of early established SLE and severe SLE (active nephritis) to define the underlying molecular aberrancies of step-wise progression from healthy state to mild/non-specific and clinical overt autoimmunity.
Lupus exists in preclinical form (i.e., before it is clinically obvious) for a period of several months or even years, during which period serological abnormalities such as positive anti-nuclear antibodies (ANAs) may be detectable. However, not all individuals with positive ANA will develop lupus. In this project, we have monitored a large group of individuals with positive ANA or mild clinical features, to determine who are at high-risk to progress into lupus. After about 18 months of follow-up, about 12% of these individuals developed lupus. We are currently analysing their age, family and obstetrical history, smoking behaviour, physical activity and diet to determine what factors determine increased propensity for lupus. Importantly, we conjecture that much of this “predisposition” is reflected into changes (variations) in the genomic make-up (i.e., expression of genes) in the blood immune system, which we will assay in order to create a prognostic “score”. These findings could be useful to provide personalized counselling and monitoring in people with positive ANAs or other signs and symptoms suggestive of lupus.