TY - JOUR
T1 - Electron microscopy study of genesis and dynamics of immunodeposition in IgMk-IgG cryoglobulin-induced glomerulonephritis in mice
AU - Fornasieri, Alessandro
AU - Tazzari, Sara
AU - Li, Min
AU - Armelloni, Silvia
AU - Tarelli, Laura Torri
AU - Sessa, Adalberto
AU - D'Amico, Giuseppe
PY - 1998/3
Y1 - 1998/3
N2 - Cryoglobulinemic glomerulonephritis is particularly frequent in type II mixed IgMk-IgG cryoglobulinemia. The typical form is a membranoproliferative glomerulonephritis with a particular monocyte infiltration. In 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 aggregates of IgG-IgM immune complexes, probably favored by high endocapillary 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 glomerulonephritis in mice by injecting them twice a day for 3 days with 4 mg human IgMk-IgG cyroglobulins previously solubilized at 37°C. The dynamic 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 quantify the contracts between such 'thrombi' and mesangial or subendothelial deposits, we obtained serial, ultrathin, 0.5-μm sections that allowed us to reconstruct the whole glomerular tuft. Within each serial section, there was continuity between hyaline thrombi and mesangial or subendothelial deposits ranging from 80% to 85% of the capillary loops. The percentage was 100% for two adjacent serial sections. In conclusion, our data demonstrate directly for the first time that hyaline thrombi follow mesangial deposits. The high percentage of contacts between thrombi and mesangial or subendothelial deposits suggests that they result from in situ build-up of true huge endoluminal immunodeposits after saturation of the clearance capacity of the mesangium.
AB - Cryoglobulinemic glomerulonephritis is particularly frequent in type II mixed IgMk-IgG cryoglobulinemia. The typical form is a membranoproliferative glomerulonephritis with a particular monocyte infiltration. In 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 aggregates of IgG-IgM immune complexes, probably favored by high endocapillary 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 glomerulonephritis in mice by injecting them twice a day for 3 days with 4 mg human IgMk-IgG cyroglobulins previously solubilized at 37°C. The dynamic 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 quantify the contracts between such 'thrombi' and mesangial or subendothelial deposits, we obtained serial, ultrathin, 0.5-μm sections that allowed us to reconstruct the whole glomerular tuft. Within each serial section, there was continuity between hyaline thrombi and mesangial or subendothelial deposits ranging from 80% to 85% of the capillary loops. The percentage was 100% for two adjacent serial sections. In conclusion, our data demonstrate directly for the first time that hyaline thrombi follow mesangial deposits. The high percentage of contacts between thrombi and mesangial or subendothelial deposits suggests that they result from in situ build-up of true huge endoluminal immunodeposits after saturation of the clearance capacity of the mesangium.
KW - Cryoglobulinemia
KW - Experimental nephritis
KW - Glomerular immunodeposits
KW - Glomerulonephritis
KW - Rheumatoid factor
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M3 - Article
C2 - 9506680
AN - SCOPUS:0031940189
VL - 31
SP - 435
EP - 442
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
SN - 0272-6386
IS - 3
ER -