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.

Keywords: Form cell; Lipoprotein glomerulopathy; Macrophage; apoE Tokyo/Maebashi; apoE2.

Fig. 1

Light microscopic findings of the first biopsy. a Lipoprotein thrombi (arrow) and foam cells (arrowhead) are observed within the same glomerulus. b-d Immunohistochemical studies using serial sections: Strong staining for both apoB (b) and apoE (c) is observed at lipoprotein thrombi, and positivity for apoE is also observed at sites other than the lipoprotein thrombi within the glomeruli. d CD68+ foam cells (arrowheads) have infiltrated in the apoE-positive part other than lipoprotein thrombi (arrow).

Fig. 2

Electron microscopic findings of the first biopsy. Intra-capillary lipoprotein thrombus-like substances (a) and foamy changes (b) are observed.

Fig. 3

a ApoE phenotype determined by isoelectric focusing polyacrylamide gel electrophoresis (IEF). Lane 1, apoE1/2 (patient); lane 2, apoE2/3; lane 3, apoE2/2; lane 4, apoE3/3 (wild type); lane 5, apoE4/4. b ApoE genotype examined by restriction fragment length polymorphism (RFLP). PCR-amplified DNA of the apoE gene, including codons 112 and 158, was digested with HhaI. Lane 1, DNA size marker; lane 2, patient; lane 3, ε3/3; lane 4, ε2/2; lane 5, ε3/4. In lane 2, the 91-, 78-, and 36-bp fragments which are consistent with ε2, are observed. Moreover, there are also 30-bp and around 60-bp fragments that are not observed in ε2, ε3, and ε4. c, d Sequence analysis of PCR-amplified DNA of the apoE gene. c A 9-bp deletion (3-amino acid deletion) in codon 141 to codon 143 of the apoE gene is observed. There are overlaps of nucleotide peaks before codon 144, indicating that the apoE alleles are heterozygous. d Both the sequence CGC (arginine; wild type) and the sequence TGC (cysteine) are observed in codon 158 of the apoE gene, indicating that the apoE2 (Arg158Cys) alleles are heterozygous.