Experimental Immunoglobulin A Nephropathy Induced by Gram-Negative Bacteria (1)

On the basis of clinical and experimental observations, a number of etiologic candi­dates for IgA nephropathy have already been suggested. Interaction of viral, bacterial or dietary antigens with the host mucosa may play an important role in the initial step of development of IgA nephropathy. Defective clearance of IgA immune complexes by hepatocytes or the reticuloendo­ thelial system seems to be a common feature in the pathogenesis of glomerular IgA and C3 deposition in these diseases.

There was constant deposition of IgM from a mild to moderate degree and variable positivity for IgG up to a mild degree in the mesangium from 10 to 30 weeks of age. Mice treated by intraperitoneal injection of H. influenzae showed a real positivity for IgA and C3 in the mesangium and paramesangial area, and histologically, the glomeruli showed mild mesangial thickening with hyper- cellularity in the mesangium, often with mesangial interpo­sition.

Sequential glomerular deposition of IgA and C3 are shown. The incidence of glomerular IgA deposi­tion in the mice of each IP subgroup was 37-71% for those that received gram-negative bacteria and 10-11% for those that received LPS. The higher incidence of glomerular deposi­tion of IgA and C3 among the IP subgroups that received gram-negative bacteria was statistically significant.

Mesangial deposition of IgA and C3 was observed more frequently and more intensely in the groups treated by intraperitoneal injection of bacterial cell precipitate (P subgroups).

Serum IgA was increased from 10- to 20-fold on average at 30 weeks of age in mice that received each antigen as well as FCA intraperitoneally. There was a significant increase in IgA specific for each antigen in comparison with the IP groups that received PBS or FCA.

Oral intake of gluten in regular fodder can induce glomerular IgA deposition in BALB/c mice. Induction of glomerular IgA deposition has been at­ tempted using a number of experimental approaches, in­cluding intraperitoneal injection of dextran or apoferritin into mice, intravenous injection of pretreated IgA-dinitrophenyl immune complexes into mice, oral administration of heterologous antigens, bile duct ligation in mice, and oral administra­tion of gluten or feeding of vomitoxin to mice.

1. Y. Endo, H. Kanbayashi, M. Hara, Experimental immunoglobulin A nephropathy induced by gram-negative bacteria. Nephron. 65, 196–205 (1993).