Prospects and Perspectives on IgA Nephropathy from Animal Models

Abstract

The focus of this chapter is a systematic and critical review of the insights that experimental models have contributed to our understanding of IgA nephropathy (IgAN). We consider the generation of IgA subject to glomerular deposition, the partitioning of IgA between the circulation and glomeruli, the clearance of IgA and complexes containing IgA from the circulation, the 'upstream' effectors of glomerular pathophysiology, the inflammatory mediators that connect intraglomerular stimuli to functional and morphologic effects, and the contribution of animal models to our current understanding of the role that glycosylation of IgA plays in the genesis of IgAN. In each of these subsections, the evidence in favor of each principle or hypothesis is weighed in consideration of other potentially contradictory evidence and relevant issues related to IgAN in patients. The key limitations of each model system are presented, and where possible, reconciliation of discrepant observations are proposed. Subsequently, a synopsis of spontaneous models that do not offer particular mechanistic insights, and a compilation of experimental therapeutic initiatives, are reviewed. In all respects, the discussion of observations in patients or cells in vitro is limited to points where these data impinge upon interpretation of the data derived from the animal models.

Animal models of kidney inflammation in translational medicine

“…But the use of this model is limited by lot-to-lot variations apoferritin preparations that reliably induce IC-GN. Several models of IgA nephropathy (IgAN) link mesangial IgA deposition, complement activation, mesangioproliferative GN, and proteinuria [6]. Such models may reliably mimic the aspect of glomerular inflammation and progression to glomerulosclerosis.…”

Follicular dendritic cell secreted protein FDC-SP controls IgA production

“…A few other mouse models of IgAN have been described, including the ddY mouse and B cell activating factor transgenic mice. 36 B cell activating factor transgenic mice produce a more severe, acute form of IgAN with very large elevation of IgA and IgG and significant kidney pathology affect both males and females. 25,37 The ddY mouse exhibits spontaneous glomerular IgA deposition and provides a multigenic disease model.…”

Induction of IgA Deposits and Glomerulonephritis by IgA Rheumatoid Factor

“…The authors explore the nephritogenic potential of two different monoclonal IgA rheumatoid factors (designated as [6][7][8][9][10][11][12][13][14][15][16][17][18][19] IgA and 46-42 IgA) specific for murine IgG2a in relation to potential differences in glycosylation of these IgA antibodies.…”

“…Almost all of the increased prevalence of albuminuria over the prior decade could be explained by increased prevalence of hypertension, diabetes, and obesity, suggesting that increased prosperity in the so-called developing world will bring an increased burden of proteinuric CKD. 8,9 In JASN, the work by Sandoval et al 10 presents a detailed description of factors influencing the accuracy of a recently developed technique (two-photon intravital microscopy) that has unexpectedly lent support to a controversial…”