Absence of Tubuloreticular Inclusions In a Transgenic Mice Model of Lupus-Like Nephritis

Document Type

Conference Proceeding

Publication Date

3-2018

Publication Title

Laboratory Investigation

Abstract

Background: Tubuloreticular inclusion bodies (TRI), often located in the endoplasmic reticulum of glomerular endothelium, are considered relatively specific for lupus nephritis types 2 to 5, except HIV associated nephropathy. The etiology of TRI in lupus nephritis remains unclear. Our previous studies have demonstrated that gp96 transgenic (96tm) mice model were characteristic for lupus-like nephritis, similar to human types 2 and 3 lupus nephritis; they were associated with high serum levels of ANA and double-stranded DNA, immunofluorescent deposition of immunoreactants and immune complex deposits as seen in 96tm (J of Immunology 2006; 177: 6880-6888). The aim of this study was to scrutinize TRI by electron microscopy (EM) in 96tm mice for potential etiology of TRI. Design: 30 genetically engineered mice were divided into two broad groups: Group 1: wild-type (WT)/ negative control mice (n=15) and Group 2: transgenic mice (n=15). Negative control mice did not express functional Toll-like receptor (TLR-/- mice) or Toll-IL-1R domaincontaining adapter protein (TIRAP-/- mice), whereas the transgenic mice expressed surface gp96. These were further divided into pure 96tm mice, TLR-/- 96tm mice and TIRAP-/- 96tm mice. They were examined using EM. Location of electron dense deposits was graded as 0 (no deposit), 1+ (minimal deposits in mesangium), 2+ (mesangial expansion by deposits) and 3+ (with subendothelial deposits). TRIs were carefully searched for, in glomerular subendothelial and epithelial cells. Results: Controls were either negative for deposits or showed minimal deposits. Type II and type III lupus nephritis demonstrated mesangial and subendothelial deposits (Table 1). Additional modification of TLR or TIRAP in transgenic mice showed partial reduction in deposits. However, none of the control or transgenic mice kidneys presented with any TRI in the glomerular endothelial or epithelial cells. Conclusions: We failed to identify TRI in this model of lupus-like nephritis, raising 2 possibilities: 1. Transgenic mice model does not fulfill all the criteria and might not be entirely representative of human lupus nephritis. 2. In our experience TRI are more common with type 3 and 4 lupus nephritis. Hence, we propose that type 2 and 3 lupus nephritis in 20 weeks old mice might not have reached a level of renal damage yet.

Volume

98

Issue

Suppl 1

First Page

806

Comments

United States and Canadian Academy of Pathology (USCAP) 107th Annual Meeting, March 17-23, 2018, Vancouver, BC, Canada

Last Page

806

DOI

10.1038/labinvest.2018.24

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