A prediction score for individuals at risk for Systemic Lupus Erythematosus (SLE) by integrating clinical, serologic and transcriptomic data

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.

• Suspected systemic rheumatic diseases in patients presenting with cytopenias. Nikolopoulos D, Adamichou C, Bertsias G. Best Pract Res Clin Rheumatol. 2019 Aug;33(4):101425. doi: 10.1016/j.berh.2019.06.007.
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• In an early SLE cohort the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria classify non-overlapping groups of patients: use of all three criteria ensures optimal capture for clinical studies while their modification earlier classification and treatment. Adamichou C, Nikolopoulos D, Genitsaridi I, Bortoluzzi A, Fanouriakis A, Papastefanakis E, Kalogiannaki E, Gergianaki I, Sidiropoulos P, Boumpas DT, Bertsias GK. Ann Rheum Dis. 2020 Feb;79(2):232-241. doi: 10.1136/annrheumdis-2019-216155.
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• An Update on the Diagnosis and Management of Lupus Nephritis. Kostopoulou M, Adamichou C, Bertsias G. Curr Rheumatol Rep. 2020 Jun 4;22(7):30. doi: 10.1007/s11926-020-00906-7.
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• Update on the diagnosis and management of systemic lupus erythematosus. Fanouriakis A, Tziolos N, Bertsias G, Boumpas DT. Ann Rheum Dis. 2021 Jan;80(1):14-25. doi: 10.1136/annrheumdis-2020-218272.
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• Lupus or not? SLE Risk Probability Index (SLERPI): a simple, clinician-friendly machine learning-based model to assist the diagnosis of systemic lupus erythematosus. Adamichou C, Genitsaridi I, Nikolopoulos D, Nikoloudaki M, Repa A, Bortoluzzi A, Fanouriakis A, Sidiropoulos P, Boumpas DT, Bertsias GK. Ann Rheum Dis. 2021; doi: 10.1136/annrheumdis-2020-219069
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EULAR Abstracts

2020

• Comparative transcriptome analyses across tissues and species identify targetable genes for human Systemic Lupus Erythematosus (SLE) and Lupus Nephritis (LN). E. Frangou, P. Garantziotis, M. Grigoriou, A. Banos, N. Panousis, E. Dermitzakis, G. Bertsias, D. Boumpas, A. Filia. (EULAR 2020, Poster Presentation THU0014).
• A multicenter “at-risk” cohort for the discovery of environmental, clinical and molecular predictors for the transition into systemic lupus erythematosus (SLE). C. Adamichou, D. Nikolopoulos, M. Nikoloudaki, Z. Rahme, M. Fredi, A. Pieta, A. Repa, A. Parma, E. Kalogiannaki, N. Avgustidis, N. Kougkas, A. Banos, A. Eskitzis, A. Bortoluzzi, S. Jacobsen, P. Sidiropoulos, E. Dermitzakis, M. Mosca, L. Inês, L. Andreoli, A. Tincani, A. Fanouriakis, G. Bertsias. (EULAR 2020, Poster Presentation FRI0155).
   

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