Elsevier

Laboratory Investigation

Volume 84, Issue 1, 1 January 2004, Pages 63-70
Laboratory Investigation

Article
Age-dependent decrease of polymeric Ig receptor expression and IgA elevation in ddY mice: a possible cause of IgA nephropathy

https://doi.org/10.1038/labinvest.3700012Get rights and content
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Abstract

Individual animals in the closed colony population of ddY mice were analyzed to clarify the major cause of age-dependent elevation of serum IgA and the appearance of human IgA nephropathy (IgAN)-like symptoms. Based on the serum IgA levels, the mice were classified into two subgroups. One was a high serum IgA group with some manifestations of IgAN through aging (ddYHigh), and the other was a normal serum IgA group without IgAN (ddYNorm). The ratio of urinary IgA to serum IgA was significantly reduced in ddYHigh mice, suggesting an impaired IgA clearance via secretion through the epithelial barrier. The actual clearance rate of the intravenously injected dimeric IgA in ddYHigh mice was found to be slower than that in ddYNorm mice. Furthermore, we found that the polymeric Ig receptors (pIgRs) that mediate transcytosis of IgA were poorly expressed in the glomeruli as well as in the intestine of ddYHigh mice, whereas the pIgRs were more abundantly expressed in ddYNorm mice. In addition, the comparative study using polymerase chain reaction showed that decreased pIgR expression occurred at the transcriptional level in the ddYHigh population. Taken together, these results suggest that a systemic defect in pIgR expression may result in impaired IgA secretion and accumulation of IgA in the serum of ddYHigh mice. The age-dependent changes of pIgR expression in the dimeric IgA secretion sites of ddYHigh mice suggest a possible cause for the elevation of serum IgA level and the pathogenesis of IgAN-like disease.

Keywords

IgA nephropathy
pIgR
ddY mice
RT-PCR
mucosal immunity

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