ELECTRON-MICROSCOPY STUDY OF GENESIS AND DYNAMICS OF IMMUNODEPOSITIONIN IGMK-IGG CRYOGLOBULIN-INDUCED GLOMERULONEPHRITIS IN MICE

Cryoglobulinemic glomerulonephritis is particularly frequent in type I I mixed IgMk-IgG cryoglobulinemia. The typical form is a membranoproli ferative glomerulonephritis with a particular monocyte infiltration. I n the most severe cases, there is occlusion of the capillary lumina by the same immunoglobulin constituents of the cryoprecipitate. While it is generally accepted that the ''hyaline thrombi'' are endoluminal ag gregates of IgG-lgM immune complexes, probably favored by high endocap illary concentration of cryoglobulins, the modality of generation has not been studied. To study the dynamic formation of such ''thrombi,'' we reproduced an experimental model of cryoglobulinemic glomerulonephr itis in mice by injecting them twice a day for 3 days with 4 mg human IgMk-lgG cryoglobulins previously solubilized at 37 degrees C. The dyn amic formation of immunodeposits was studied by immunofluorescence and electron microscopy. After 1 day, only mesangial deposits were found; after 3 days, in addition to mesangial deposition, all the capillary lumina were occluded by huge electron-dense bodies. To look for and qu antify the contacts between such ''thrombi'' and mesangial or subendot helial deposits, we obtained serial, ultrathin, 0.5-mu m sections that allowed us to reconstruct the whole glomerular tuft. Within each seri al section, there was continuity between hyaline thrombi and mesangial or subendothelial deposits ranging from 80% to 85% of the capillary l oops. The percentage was 100% for two adjacent serial sections. In con clusion, our data demonstrate directly for the first time that hyaline thrombi follow mesangial deposits. The high percentage of contacts be tween thrombi and mesangial or subendothelial deposits suggests that t hey result from in situ build-up of true huge endoluminal immunodeposi ts after saturation of the clearance capacity of the mesangium. (C) 19 98 by the National Kidney Foundation, Inc.