by Eleni A. Frangou, Clinical Professor, Department of Basic and Clinical Sciences, UNIC Medical School.
Introduction by Professor Aleksandar Jovanovic, Head of the Department of Basic and Clinical Sciences, UNIC Medical School.
Systemic Lupus Erythematosus (SLE) is the prototypic systemic autoimmune disease characterized by damage in multiple organs, such as the skin, joints, nervous system, and the kidneys. Lupus mainly affects individuals of childbearing age and is highly heterogeneous in clinical manifestations, severity, and response to treatment. Despite efforts, the pathogenesis remains elusive, treatment is empirical, and morbidity and mortality remain increased.
Using state-of-the art technologies (such as transcriptomics, imaging, and functional analyses), a novel multistep pathway mediating kidney injury in lupus that can be targeted at multiple stages through drug repositioning was identified. A comparative cross-tissue (spleen, brain, kidney, blood) and cross-species (mice and humans) transcriptome analysis further identified genes and pathways associated with the progression from the pre-clinical stage to full blown disease. Using mouse genes as predictors of human disease, a machine-learning algorithm predicting those lupus patients that will develop kidney damage in the future was developed. Finally, computational systems analyses prioritized common cross-species genes as kidney-specific therapeutic targets in lupus.
Application of these techniques and approaches can extend beyond lupus and the kidneys, and may guide us towards precision medicine, the medicine that identifies the right therapy to be given to the right patient at the right time.