SLE is the prototypic autoimmune disease and efforts are underway to better understand its cause and find new therapeutic approaches. To this end, we conducted a study where samples of SLE patients were analyzed to provide further insights into molecular (genomic) markers that predict the disease course, the response to different therapies and the damage caused by the disease to different tissues. For the first task, we used cutting edge biological and informatic approaches. Our identified novel genes and pathways that contribute to disease flares, severity and specific manifestations such as nephritis, which might be further explored as potential therapies. Following these analyses, we mapped a list of 15 genes that can predict major organ involvement (kidney, brain, etc.) in a given SLE patient, based upon the pattern of gene expression of these genes. Our analysis also confirmed the critical role of the immune system (e.g. over-expression of the antiviral interferon-alpha) in the causation of the SLE. These results could potentially assist the early diagnosis of SLE. Of interest, combining genetic variation (i.e. inter-individual changes in the DNA) with gene expression, we showed that besides immune cells in the blood, other organs such as the liver and the brain are involved in causing the disease.
In other studies run in parallel, we discovered that mouse and human bone marrow (the organ that makes the cells of the blood) in SLE produce more cells that cause inflammation. Moreover, a specific type of blood cells (neutrophils) is produced in a totally different fashion in SLE compared to healthy individuals. The comparison of hematopoietic progenitors between mice and humans provides a more clear picture of the biology of the lupus hematopoietic stem cell and a better understanding how bone marrow is involved in lupus.