Immunoglobulin-A Nephropathy with Crescentic Glomerulonephritis in a Pigtailed Macaque (Macaca nemestrina)

Abstract

Abstract.A 4-year-old female pigtailed macaque (Macaca nemestrina), experimentally coinfected with simian immunodeficiency virus (SIVmac251) and Mycobacterium bovis (bacillus Calmette-Guerin), was euthanatized 1 year after infection because of weight loss and labored breathing. On gross examination, both kidneys were found to be markedly enlarged (right: 54.7 g and left: 51.7 g; normal Ͻ 20 g). Renal lesions were evaluated by histopathologic, immunohistochemical, and ultrastructural methods. Light microscopy revealed that the glomeruli were diffusely hypercellular with expansion of the mesangial matrix, and crescent formation affected approximately 60% of the glomeruli. By immunohistochemical evaluation, it was found that the crescents were composed principally of macrophages, as seen by CD68 (KP1), MRP8, MAC387, and HAM56 expression. Electron microscopic examination of the glomeruli revealed extensive intramembranous, subendothelial, and mesangial electron-dense deposits and multifocal fusion of the visceral epithelial foot processes. Immunofluorescence, used to determine the composition of the electron-dense deposits, revealed diffuse granular mesangial and capillary staining for immunoglobulin A (IgA). The renal changes described in this case report are most consistent with the findings of crescentic gloerulonephritis with IgA immune complex deposition in the glomerular basement membrane and mesangium as described in humans with IgA nephropathy.

Using the Pathogenic and Nonpathogenic Nonhuman Primate Model for Studying Non-AIDS Comorbidities

“…Other SHIV-infected macaques presented with nephrotic syndrome, characterized by peripheral edema, hypoalbuminemia, and proteinuria [ 91 ]. A case of immunoglobulin-A nephropathy with crescentic glomerulonephritis was described in a PTM coinfected with SIVmac and Mycobacterium tuberculosis [ 92 ]. Finally, we previously described a high frequency of thrombotic microangiopathy (TMA) in the SIVsab-infected PTMs [ 33 ••], a condition described in HIV patients which is associated with a poor prognostic and accelerated death [ 67 ].…”

Pathological changes in nephritis cases of non‐human primates in Assam

“…No deposition was recorded in the present study in routine H&E sections. Borda et al 4 . recorded nephritis in a pig tailed macaque where the renal changes were most consistent with crescentic glomerulonephritis with IgA immune complex deposition in the glomerular basement membrane.…”

“…The first case of fibrillary glomerulonephritis with pulmonary‐renal syndrome in Amazonian Woolly monkey ( Lagothrix lagotricha ) was reported by Brown et al 3 . Borda et al 4 experimentally co‐infected a pigtailed macaque with simian immunodeficiency virus and Mycobacterium bovis where the glomeruli were diffusely hypercellular with expansion of the mesangial matrix and crescent formation in the affected glomeruli. The renal changes were most consistent with the findings of crescentic glomerulonephritis with IgA immune complex deposition in the glomerular basement membrane.…”

Prospects and Perspectives on IgA Nephropathy from Animal Models

“…In addition to the aforementioned spontaneous IgAN that arises in primates [55,56], macaques infected with simian immunodeficiency virus (with or without complicating infection with M. bovis) also develop IgAN [159] or an IgAN-like glomerulonephritis [160]. In pigs, spontaneous IgAN is associated with mycoplasma infection [161], and feeding nivalenol induces IgAN [162] similar to that provoked in mice by this dietary toxin [53].…”