Macrophage Infiltration into the Glomeruli in Lipoprotein Glomerulopathy

Abstract

Lipoprotein glomerulopathy (LPG) is characterized by histopathological features showing intra-glomerular lipoprotein thrombi and type III hyperlipoproteinemia (HLP), with heterozygote mutation of apolipoprotein (apo) E gene. On the other hand, as another renal lipidosis with type III HLP, apoE2 homozygote-related glomerulopathy (apoE2-GN) showing foamy macrophages has been reported. The case of a 25-year-old man who had LPG by clinical behavior and gene analysis, but demonstrated atypical histopathological features with a substantial amount of foamy macrophage infiltration in the glomeruli, is presented. The combination of alleles for apoE Tokyo/Maebashi and classical apoE2 (Arg158Cys) was inferred to be the leading cause of the unique renal pathology with lipoprotein thrombi and foamy macrophages. In addition, foamy macrophages infiltrated some part of the apoE-positive region within the glomerulus, but did not exist in lipoprotein thrombi despite apoE positivity, suggesting that properties of apoE are crucial in the development of LPG rather than macrophage function. This case provides important information related to the pathogenesis of LPG and apoE2-GN.

Pathogenesis, histopathologic findings and treatment modalities of lipoprotein glomerulopathy: A review

“…Furthermore, Ito et al38 generated LPG-like changes in ApoE and FcRγ double-knockout mice by injecting various apoE vectors. These results suggest that macrophage impairment may be one of the mechanisms responsible for the development of lipoprotein thrombi and the absence of macrophages in LPG 2…”

“…Lipoprotein glomerulopathy (LPG) is a rare autosomal recessive disorder, which determines marked proteinuria and progression to kidney failure. The compromised glomeruli exhibit ectatic capillary lumina occupied by lipoprotein thrombi 1 , 2 , 3. LPG typically compromises Asian patients, in special Japanese, and males outnumber females two to one.…”

“…LPG typically compromises Asian patients, in special Japanese, and males outnumber females two to one. Serum levels of lipoprotein are typically increased especially β-lipoprotein and pre-β-lipoprotein 2 , 4 , 5 , 6. LPG can resemble type III hyperlipoproteinemia, but atherosclerosis, corneal arcus, and cutaneous xanthomas are very uncommon.…”

Apolipoprotein E–related glomerular disorders

“…One case 23 with apoE2/3 was associated with marked non-immune subendothelial EDDs. The other case 24 had the combination of heterozygous apoE2 and apoE Tokyo/Maebashi 25,26 isoforms and showed infiltration of foamy macrophages in addition to lipoprotein thrombi. As apoE Tokyo/Maebashi, 25,26 an in-frame deletion of Leu141 to Lys143, is one of the representative mutations for LPG, atypical histopathologic changes may be induced by a compound heterozygote.…”

A case of diagnosing lipoprotein glomerulopathy in Russia

“…С другой стороны, вариант мутации Kyoto (Cys 25 Arg) располагается далеко от рецепторсвязующего домена и сопровождается системным липидозом и гиперлипидемией, демонстрируя повышенную связующую активность эндотелия капилляров клубочка [17]. В последних исследованиях [19] установлено, что комбинация аллелей, например АpoE Tokyo/Maebashi и apoE2 (Arg158Cys), вносит дополнительные изменения в патоморфологическую картину заболевания.…”