Experimental Glomerulonephritis Induced with the Major Antigen of Rat Kidney

Abstract

The major antigen of rat kidney (KMA) isolated in an immunochemically purified form was injected into homologous rats at 2-week intervals during 42 weeks. Circulating antibodies against KMA were constantly found in the sera of all immunized animals after 4 months of KMA treatment. Marked proteinuria accompanied by a significant increase in the serum γ-globulin level occurred only several months after the appearance of circulating antibodies. Histological examinations of the KMA-treated rat kidney revealed mild but definite glomerular lesions of the membranous, non-proliferative type. Rat γ-globulin was found as a mixed, linear and granular, deposit along the basement membranes and the mesangial regions. However, rat β_1C-globulin was found as an exclusively granular deposit in the same areas, but more intensively in the mesangium. The acid elution of KMA-treated rat kidney contained γ-globulin which reacted with KMA. As compared with Edgington’s nephritogenic tubular antigen RTE-α₅, KMA was found to be completely different. However, it was also localized exclusively in the proximal tubular cells. Its presence in normal rat serum and liver has been suggested as a source of autologous immunogens in the long-term development of an autoimmune complex nephritis in the rat.

Partial Purification of Human Kidney Antigens

“…The discovery of immunologi cal cross-reactivity between kidney antigens and /3-haemolytic streptococci, and also Escherichia coli [13], makes studies on kid ney-specific antigens even more important. On the basis of these findings, the cross reactions have been claimed to be at least partly responsible for the pathogenesis of glomerulonephritis and the scarring of pye lonephritis [14], Many of the problems concerning the chemistry [6,19] structure [15] and biologi cal significance [7,11,12,17] of the kid ney-specific antigens are still unsolved due to the fact that satisfactory methods of puri fying and isolating such antigens have not been developed. In a previous paper [1], in dications of the existence of kidney-specific antigens were reported.…”

Immunochemical and Enzymatic Studies on the Soluble Antigens of Normal Human Kidney

“…Concerning more specifically the kidney, we have used in our laboratories immunochemical methods to identify several mouse and rat tissue antigens [19,20]: data have also been obtained by other workers in the calf [21] and in man [22,23]. Moreover, we have isolated and characterized the kidney major antigen (KMA) [24] and showed its nephritogenic effects in homologous rat [25]: E d g in g t o n et al [I] have also characterized a kidney tubular antigen with nephritogenic activity: McPhaul and D ixon [26] have isolated a glomerular basement membrane antigen in normal adult serum and urine. Even with all this knowledge, the behavior of most of the kidney tissue antigens is still obscure.…”