New insights into the pathogenesis of IgA nephropathy

Abstract

IgA nephropathy is the most common form of glomerulonephritis in many parts of the world and remains an important cause of end-stage renal disease. Current evidence suggests that IgA nephropathy is not due to a single pathogenic insult, but rather the result of multiple sequential pathogenic “hits”. An abnormally increased level of circulating poorly O-galactosylated IgA1 and the production of O-glycan-specific antibodies leads to the formation of IgA1-containing immune complexes, and their subsequent mesangial deposition results in inflammation and glomerular injury. While this general framework has formed the foundation of our current understanding of the pathogenesis of IgA nephropathy, much work is ongoing to try to precisely define the genetic, epigenetic, immunological, and molecular basis of IgA nephropathy. In particular, the precise origin of poorly O-galactosylated IgA1 and the inciting factors for the production of O-glycan-specific antibodies continue to be intensely evaluated. The mechanisms responsible for mesangial IgA1 deposition and subsequent renal injury also remain incompletely understood. In this review, we summarize the current understanding of the key steps involved in the pathogenesis of IgA nephropathy. It is hoped that further advances in our understanding of this common glomerulonephritis will lead to novel diagnostic and prognostic biomarkers, and targeted therapies to ameliorate disease progression.

Effects of Hydroxychloroquine on Proteinuria in Immunoglobulin A Nephropathy

“…Theoretically, HCQ can suppress innate immune system activation by mucosal antigens via TLR inhibition, which results in reduced mucosal IgA-committed B cell proliferation [18]. Because the mis-homing of these mucosal B cells to bone marrow may be the source of Gd-IgA1 in the circulation [18], serum Gd-IgA1 levels may be reduced with HCQ therapy.…”

Association of CD147 renal expression with morphologic lesions of Oxford classification in IgA nephropathy patients

“…Immunoglobulin A (IgA) nephropathy can be considered as deposits of IgA in mesangial area of glomeruli or mesangiocapillary region, which may result in glomerular inflammation (1). Nephropathy of IgA, is the most frequent glomerulonephritis worldwide (1,2).…”

“…Nephropathy of IgA, is the most frequent glomerulonephritis worldwide (1,2). Nephropathy of IgA, has a highly variable course, either clinically or pathologically.…”

“…Clinical aspect of this disease may range from asymptomatic hematuria to a rapid course detected as a progressive glomerulonephritis (2,3). IgA nephropathy is mostly associated with the detection of microscopic hematuria or recurrent macroscopic hematuria (1)(2)(3). It is a benign disease in many patients.…”

“…Furthermore, numerous investigations have detected some clinical aspects having prognostic implication (2)(3)(4)(5). Some parameters like proportion of proteinuria, progressive kidney dysfunction and male gender have prognostic implication (1,2). Studies regarding morphological lesions, as prognostic factors for development to end-stage kidney failure in nephropathy of IgA, have reported various findings (1-3).…”