Spontaneous Mesangioproliferative Glomerulonephritis in Pigtailed Macaques (Macaca nemestrina)

Abstract

Mesangioproliferative glomerulonephritis was found in 28 of 113 pigtailed macaques (Macaca nemestrina) that died in 1977. In five it was considered severe enough to cause significant renal dysfunction; in two of these it was the cause of death. The basic lesion was a proliferation of mesangial cells and deposition of mesangial matrix in the mesangial stalk, resulting in various degrees of stalk expansion and increased lobulation of the glomerular tuft. Preliminary immunofluorescence and ultrastructural studies suggests the pathogenesis of the lesion may involve deposition of antigen-IgM immune complexes in the mesangial region.

Formation, Clearance, Deposition, Pathogenicity, and Identification of Biopharmaceutical-related Immune Complexes

“…Giddens and colleagues (1981) reported that 14% of adult nemestrine macaques dying from spontaneous disease had GN and concurrent IgM glomerular deposits. However, very limited IgM deposits thought to contribute to the pathogenesis of the severe forms of the disease in nemestrine macaques (Boyce, Giddens, and Seifert 1981) similar to the more widespread drug-ADA complexes in some of the case study monkeys (Tables 3-4). Often, the antigen is unknown in the IC-related granular deposits in spontaneous glomerular disease in monkeys.…”

“…However, very limited IgM deposits were found in clinically normal nemestrine macaques without renal disease consistent with Brack’s marmoset studies, similar to the very limited IgM deposits observed in control monkeys from case 5 (Table 1). Antigen - IgM ICs in mesangium are thought to contribute to the pathogenesis of the severe forms of the disease in nemestrine macaques (Boyce, Giddens, and Seifert 1981) similar to the more widespread drug - ADA complexes in some of the case study monkeys (Tables 3–4).…”

“…4, 2014 IMMUNE COMPLEXES IN MONKEYS AND OTHER SPECIES randomly selected adults; 20 were aged 2 to 3 years, 12 were aged 7 to 8 years IgM deposits in mesagium or along glomerular basement membrane in 72% IgG, C1q, C4, and C3 granular deposits in 30% TEM-dense granular deposits along glomerular basement membrane and in subepithelial and mesangial locations Greatest increases in IgM deposits were in animals with decreased serum C3, igM, and IgA Persistent, nonprogressive disease over 3 to 11 months; no defined relationship to age No associated renal insufficiency with normal serum BUN, creatinine Poskitt et al (1974) Pigtailed macaques (Macaca nemestrina) " mesangial cells/matrix w/thickening of capillary walls IgM deposits in glomeruli common 14% of adults with spotaneous disease deaths had ''asymptomatic'' mesangioproliferative glomerular disease No clear relationship between IgM and mesangioproliferative disease Giddens et al (1981) Antigen-IgM ICs might contribute to pathogenesis of severe mesangioproliferative glomerular disease? Boyce, Giddens, and Seifert (1981) Rhesus macaques (Macaca mulatta)…”

“…fasicularis/irus) Mesangial cells/matrix and/or glomerular basement membrane (histopathology, TEM) in 41% of the 32 randomly selected adults; 20 were aged 2 to 3 years, 12 were aged 7 to 8 years IgM deposits in mesagium or along glomerular basement membrane in 72% IgG, C1q, C4, and C3 granular deposits in 30% TEM-dense granular deposits along glomerular basement membrane and in subepithelial and mesangial locations Greatest increases in IgM deposits were in animals with decreased serum C3, igM, and IgA Persistent, nonprogressive disease over 3 to 11 months; no defined relationship to age No associated renal insufficiency with normal serum BUN, creatininePoskitt et al (1974) Pigtailed macaques (Macaca nemestrina) " mesangial cells/matrix w/thickening of capillary walls IgM deposits in glomeruli common 14% of adults with spotaneous disease deaths had ''asymptomatic'' mesangioproliferative glomerular disease No clear relationship between IgM and mesangioproliferative diseaseGiddens et al (1981) Antigen-IgM ICs might contribute to pathogenesis of severe mesangioproliferative glomerular disease?Boyce, Giddens, and Seifert (1981) Rhesus macaques (Macaca mulatta)Hyalinized/sclerotic glomeruli Proliferative arteriopathy Mononuclear cell infiltrates Skelton-Stroud and Glaister (1987) Squirrel monkey (Saimiri boliviensis) 4 types of glomerular disease, 1 is IgM predominating mesangioproliferative glomerular disease IgM deposits in glomeruli common; seem to correlate with increases in mesangial matrix Other ICs not common Unknown antigen (environmental, dietary, infections?) No electron-dense deposits in mesangium or capillary basement membrane by TEMBorda, Idiart, and Negrette (2000) …”

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

“…19 Interstitial lesions include periglomerular lymphocytic infiltrates, focal to diffuse infiltrates of lymphocytes and plasma cells in the interstitium, and linear to diffuse fibrosis of the renal parenchyma. [4][5][6][7]12 However, macaques experimentally infected with simian immunodeficiency virus (SIV) appear to have a higher incidence of MesPGN or focal segmental glo- merulosclerosis (or both). 1,11 To our knowledge, this is the first report of CGN and MesPGN associated with IgA deposition in a macaque.…”