Lupus Nephritis: Advances in the Knowledge of its Immunopathogenesis Without the Expected Therapeutic Success? Nefritis lúpica: ¿avances en el conocimiento de su inmunopatogénesis sin los esperables logros terapéuticos?

Systemic lupus erythematosus (SLE) is a polygenic and multifactorial syndrome, characterized by deep and diverse alterations in immunoregulation and loss of tolerance, and pathogenic autoantibody production is expressed by multiorgan involvement; nephritis (NL) is common and causes high morbidity and mortality.1 In SLE there is an increase in apoptosis gene dysregulation as a result of alterations in the handling and purification of nucleosomes and chromatin, formation of autoantibodies and immune cell dysfunction (antigen presenting macrophages, T and B cells). This translates into a tissue infiltration of immune cells, increased cytokine expression (interferon, interleukin 17, 6 and tumor necrosis factor, among others), and as the production of anti-DNA autoantibodies that are associated with endothelial dysfunction as well as of other cells and tissues, and their consequent failure.1 LN is accompanied by structural and functional modification of podocytes and proteins involved in tissue damage. Nucleosomal DNA and immune complexes activate TLR9 receptors on B cells, and on plasmacytoid dendritic cells. B lymphocyte stimulator (BLyS or BAFF-activating factor), proliferation-inducing ligand (APRIL) and weak inducers of apoptosis from the TNF family (TWEAK) are cytokines involved in inflammatory processes and autoimmunity. Viral and bacterial products and drugs (some that decrease DNA methylation) intrarenally stimulate immune cells, leading to proteinuria. Ultraviolet light induces apoptosis of keratinocytes, increasing the load of dead cells and their inefficient clearance and exacerbates SLE. Immune complexes are related to the type, duration and severity of LN, with mesangial, subendothelial or subepithelial deposits, and the concurrent activation of complement. The immune complexes bind to receptors (Fc and complement TLR), activate kidney cells (macrophages, dendritic cells, podocytes), attract leukocytes (via adhesion molecules and complement