Pathogenic role of (S)IgA in IgA nephropathy

Abstract

Primary IgA nephropathy (IgAN) is the most common form of primary

glomerulonephritis world wide and leads to end stage renal disease in

30-50% of patients. The hallmark of IgAN is the deposition of IgA1 in

the mesangial area of the kidney. Since the inflammatory response which leads to progressive renal disease, is triggered and sustained by the deposition of IgA in the renal mesangium, it is important to determine by which mechanisms binding to mesangial cells (MC) occurs. Most likely both the intrinsic renal features, as well as circulating factors, such as structural alterations in serum IgA molecules are thought to be involved in the pathogenesis of IgAN. In this thesis we concentrated on two aspects. First identify and further characterize the IgA binding receptors potentially playing a role in IgA nephropathy, including FcRI/CD89, Fc/µR. Furthermore, we characterized the different molecular forms of IgA with special attention to the specific glycosylation patterns. Finally, we found a clear deposition of SIgA in the glomeruli of IgA nephropathy patients. Altogether, the data presented in this thesis support a role for SIgA in the pathogenesis of a subpopulation of IgAN patients.