The Role of Glomerular and Serum Expression of Lymphocyte Activating Factors BAFF and APRIL in Patient with Membranous and IgA Nephropathies

Abstract

Increased activity of B lymphocytes underpins many autoimmune conditions. A key component of the humoral immune response involves the A PRoliferation-Inducing Ligand (APRIL) and B-cell-activating factor (BAFF) system. These proteins are responsible for the activation, maturation, and survival of B lymphocytes, playing a pivotal role in autoimmunity. Therefore, targeting the BAFF/APRIL system proves promising for the treatment of various autoimmune diseases. Meticulous research into pathomechanisms of lupus nephritis (LN) has enabled the introduction of biological treatments targeting the BAFF-mediated pathway, significantly improving prognosis. In certain types of glomerulonephritis (GN), increased levels of the BAFF/APRIL system might be associated with higher proteinuria, elevated serum creatinine, but also with specific histopathological features. This indicates that biological therapies currently available could be repurposed for conditions where increased activation of B lymphocytes plays a critical role in the disease's pathophysiology. Understanding the mechanisms underlying autoimmune diseases will facilitate the adaptation of novel drugs for orphan diseases. That is why the use of chimeric antigen receptor T (CAR-T) cells as agents against B-cells receptor (BCR), represents a highly targeted and potentially optimal treatment approach. This study summarizes current knowledge about the role of the BAFF/APRIL system in lymphocyte activation mechanisms, particularly in GN. It also discusses existing biological treatments and explores future directions for drug development based on the CAR-T cell technology.

Keywords: APRIL; BAFF; IgA nephropathy; autoimmunity; glomerulonephritis; membranous nephropathy.