Systemic lupus erythematosus (SLE) is a complex disease characterized by the appearance of autoantibodies against nuclear antigens and the involvement of multiple organ systems, including the kidneys. The precise immunological events that trigger the onset of clinical manifestations of SLE are not yet well understood. Our team has identified an important role for microRNA-21 in SLE pathogenesis through regulation of T cell responses. This is of exceptional importance since biotechnology companies are currently developing drugs against miR-21 expression. Furthermore, following a systems approach we have identified novel kinases involved in SLE pathobiology and also found a microRNA (miR-422a) regulating KLK4 expression in renal biopsies from SLE patients, suggesting that inhibition of miR-422a could have a therapeutic potential in these patients.
A. Stagakis E, Bertsias G, Verginis P, Nakou M, Hatziapostolou M, Kritikos H, Iliopoulos D, Boumpas DT. Identification of novel microRNA signatures linked to human lupus disease activity and pathogenesis: miR-21 regulates aberrant T cell responses through regulation of PDCD4 expression. Ann Rheum Dis 70:1496-506, 2011.
This was the first study showing that microRNAs are involved in the pathogenesis of systemic lupus erythematosus.
B. Nakou M, Bertsias G, Stagakis I, Centola M, Tassiulas I, Hatziapostolou M, Kritikos I, Goulielmos G, Boumpas DT, Iliopoulos D. Gene network analysis of bone marrow mononuclear cells reveals activation of multiple kinase pathways in human systemic lupus erythematosus. PLoS One 2010; 5:e13351.
C. Krasoudaki E, Banos A, Stagakis E, Loupasakis K, Drakos E, Sinatkas V, Zampoulaki A, Papagianni A, Iliopoulos D, Boumpas DT, Bertsias GK. MicroRNA analysis of renal biopsies in human lupus nephritis demonstrates up-regulated miR-422a driving reduction of kallikrein-related peptidase 4. Nephrol Dial Transplant, 2015.