Strain-specific renal toxicity of heterologous antilymphocyte gamma-globulin in mice.

Abstract

SUMMARY Severe glomerulonephritis followed one to five weekly i.p. injections in TLFM mice of rabbit antimouse lymphocyte γ-globulin (ALG). Glomerulonephritis did not occur in C57BL mice subjected to the same regimen. Administration of normal rabbit γ-globulin (NRG) to RFM mice also caused renal glomerular changes, but no obvious clinical illness or death. Electron microscopy revealed severe alterations in renal glomerular basement membranes after ALG treatment, including subepithelial deposition of electron-dense material and fusion of epithelial foot processes. Subepithelial and subendothelial deposits were seen after NRG treatment. Immunofluorescence microscopy revealed the presence of both rabbit and mouse y-globulins in damaged glomeruli after administration of ALG and NRG. These changes, together with the clinical signs, indicated that an immune complex scrum sickness nephritis followed ALG treatment in RFM mice. A mild form of the disease occurred after treatment with NRG. These results show that, dangerous hypersensitivity reactions may follow administration of highly purified ALG. The selective toxicity of ALG in RFM, but not in C57BL, mice may be related to preexisting renal or autoimmune disease in the RFM strain. The results imply a need for caution in using ALG in patients with coexisting renal disease or autoimmune disease.