1. ¹Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan
2. ²Department of Pediatrics, Nippon Medical School, Tokyo, Japan
3. ³Department of Pathology, Nihon University School of Dentistry, Tokyo, Japan
4. ⁴Yakult Central Institute for Microbiological Research, Tokyo, Japan

Correspondence: Hidemi Takahashi, Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. E-mail: htkuhkai@nms.ac.jp

Received 24 September 2003; Accepted 2 October 2003; Published online 20 November 2003.

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 (ddY^High), and the other was a normal serum IgA group without IgAN (ddY^Norm). The ratio of urinary IgA to serum IgA was significantly reduced in ddY^High mice, suggesting an impaired IgA clearance via secretion through the epithelial barrier. The actual clearance rate of the intravenously injected dimeric IgA in ddY^High mice was found to be slower than that in ddY^Norm 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 ddY^High mice, whereas the pIgRs were more abundantly expressed in ddY^Norm mice. In addition, the comparative study using polymerase chain reaction showed that decreased pIgR expression occurred at the transcriptional level in the ddY^High 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 ddY^High mice. The age-dependent changes of pIgR expression in the dimeric IgA secretion sites of ddY^High mice suggest a possible cause for the elevation of serum IgA level and the pathogenesis of IgAN-like disease.