Kidney damages mediated by the immune system have been reported for glomerular diseases, tubulointerstitial nephritis, and rejection of the allograft posttransplantation. B-lymphocytes have an important role in the pathogenesis for these kidney diseases. There are increasing evidences that TNF-like ligands which regulate B-cell homeostasis such as B-lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) can be used to detect kidney diseases as well as acute rejection of the kidney allograft. This chapter will review these two ligands, BLyS and APRIL, and its promising prospect in detecting glomerular diseases and acute rejection of the kidney allograft.
BLyS and APRIL are found in the plasma and membrane proteins of macrophages, monocytes, and dendritic cells. Both can activate the proliferation of B-cells and plasma cells. They are expressed on tissues of the lymph node, bone marrow, synovium, and kidney. Even though both cytokines share a common receptor on the B-cells, however, their roles in B-cell activation are significantly different. When BLyS is activated, this will result in severe B-cell hyperplasia in BLyS-transgenic mice. In contrast, when APRIL is activated, there is no effect on the homeostasis of the lymphoid in APRIL-transgenic mice.
BLyS was initially discovered to be a potential therapeutic target for lupus patients. Later, it was shown that both BLyS and APRIL were somehow associated with lupus nephritis. Both cytokines are expressed on the infiltrating monocytes and/or macrophages of patients with lupus nephritis. It remains unknown whether the blockade of both cytokines can be used to treat the lupus disease. However, serum APRIL has been shown to be a useful biomarker in detecting lupus nephritis in patients with a poor prognosis.
In kidney transplantation, B-cell is an important factor for the long-term survival of the kidney allograft. High levels of BLyS or APRIL can activate alloreactive B-cells by inducing antibodies against the donor antigens (donor-specific antibody, DSA) and result in rejection of the allograft. Aside from that, BLyS is an important growth factor for IL-10-producing B-cells known as the regulatory B-cells. It has been shown that BLyS from the mice can increase a proportion of regulatory B-cells ex vivo. These evidences indicate that BLyS plays a major role in the activation and regulation of the immune system affecting the success and/or outcome of the kidney transplantation.