Ultrastructural and Histochemical Mesangial Alterations in Callitrichid IgM Nephropathy (Primates: Platyrrhina)

Brack, M.; Weber, Manfred

doi:10.1159/000188472

Cited by 16 publications

(19 citation statements)

References 11 publications

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“…1,2,4 In the present study, we therefore examined details of the histopathologic characteristics of the background renal lesions in common marmosets.…”

Section: Discussionmentioning

confidence: 99%

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Spontaneous Glomerular and Tubulointerstitial Lesions in Common Marmosets (Callithrix jacchus)

Isobe¹,

Adachi²,

Hayashi³

et al. 2011

Vet Pathol

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Spontaneous progressive nephropathy dominated by glomerular lesions in common marmosets has been reported. However, the histopathologic characteristics, including the relationship between glomerular and tubulointerstitial lesions, have not been described in detail. In the present study, the authors examined the histopathologic characteristics of the background renal lesions in common marmosets (3 males and 9 females, 3 to 8 years old). The severity of glomerular lesions was graded into 3 classes: grade I, no alteration; grade II, hilar/focal increase of mesangial matrix; grade III, global/diffuse increase of mesangial matrix. Tubulointerstitial lesions (tubular regeneration and hyperplasia and interstitial inflammation and fibrosis) were scored according to the area of each lesion. The renal lesions were characterized by enlargement of glomeruli, expanded mesangial area with increase of periodic acid-Schiff reaction-positive matrix, tubular regeneration and hyperplasia, and interstitial inflammation and fibrosis. Glomerular lesions progressed with increasing mesangial matrix and aging. Additionally, the tubulointerstitial lesions became exacerbated with progressing glomerular lesions. Tubular hyperplasia was divided into 4 types according to the structure of the cell layer (simple or stratified-like), the area of increased lining cells (partial or entire), cytoplasmic staining (eosinophilic or basophilic), brush border and thickness of basement membrane, and the activity of cell proliferation. In conclusion, the background renal lesions in common marmosets were characterized by glomerular lesions with increase of mesangial matrix, which progressed with aging, and secondary tubulointerstitial lesions, including tubular hyperplasia. Those lesions were thus diagnosed as progressive glomerulonephropathy in common marmosets.

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“…1,2,4 In the present study, we therefore examined details of the histopathologic characteristics of the background renal lesions in common marmosets.…”

Section: Discussionmentioning

confidence: 99%

“…2,4 The nephropathy was characterized by mesangial proliferative glomerulonephritis (increase of mesangial cells and matrix) and tubulointerstial nephritis. The pathogenesis of the disease is yet unknown, although participation of IgM and IgA has been reported.…”

mentioning

confidence: 99%

Spontaneous Glomerular and Tubulointerstitial Lesions in Common Marmosets (Callithrix jacchus)

Isobe¹,

Adachi²,

Hayashi³

et al. 2011

Vet Pathol

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“…C1q and C4 also have been demonstrated (Poskitt et al 1974). When sequential studies of spontaneous IC deposition and GN/glomerulopathy are performed, it appears that mesangial granular IgM deposits precede histologic evidence of pathology (Brack 1995;Brack and Weber 1995). Giddens and colleagues (1981) reported that 14% of adult nemestrine macaques dying from spontaneous disease had GN and concurrent IgM glomerular deposits.…”

Section: Ihc Findings In Monkey Glomerular Diseasementioning

confidence: 99%

“…) No electron-dense deposits in mesangium or capillary basement membrane by TEM Borda, Idiart, and Negrette (2000) Common marmoset (Callithrix jacchus) Mesangial IgM deposits in early infancy without histologic alterations Mesangial lesions appear at 3 months, increase between 4 and 12 months of age Early lesions consisted of symmetrical (axial) proliferation of mesangial cells and matrix Later lesions characterized by excessive mesangial matrix deposition Brack and Fooke (1991), Brack (1988), Brack (1995), Brack and Rothe (1981), Brack and Weber (1995) Baboon (Papio cynocephalus) 27/60 catheterized baboons 15 had mesangioproliferative GN with proteinuria, hypoalbuminemia, generalized edema (nephritic syndrome?) 8/10 sepsis (2/10 had septic catheter) Herellea sp., Streptococcus sp., Klebsiella sp., Staphylococcus sp., Providencia sp.…”

Section: Systemic or Generalized Drug-ada Ic Formation Associated Witmentioning

confidence: 99%

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

et al. 2014

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Vascular inflammation, infusion reactions, glomerulopathies, and other potentially adverse effects may be observed in laboratory animals, including monkeys, on toxicity studies of therapeutic monoclonal antibodies and recombinant human protein drugs. Histopathologic and immunohistochemical (IHC) evaluation suggests these effects may be mediated by deposition of immune complexes (ICs) containing the drug, endogenous immunoglobulin, and/or complement components in the affected tissues. ICs may be observed in glomerulus, blood vessels, synovium, lung, liver, skin, eye, choroid plexus, or other tissues or bound to neutrophils, monocytes/macrophages, or platelets. IC deposition may activate complement, kinin, and/or coagulation/fibrinolytic pathways and result in a systemic proinflammatory response. IC clearance is biphasic in humans and monkeys (first from plasma to liver and/or spleen, second from liver or spleen). IC deposition/clearance is affected by IC composition, immunomodulation, and/or complement activation. Case studies are presented from toxicity study monkeys or rats and indicate IHC-IC deposition patterns similar to those predicted by experimental studies of IC-mediated reactions to heterologous protein administration to monkeys and other species. The IHC-staining patterns are consistent with findings associated with generalized and localized IC-associated pathology in humans. However, manifestations of immunogenicity in preclinical species are generally not considered predictive to humans.

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“…Glomerular sclerosis and tubulointerstitial nephritis were found in the advanced lesions. Previously, these renal lesions were described as ''IgM nephropathy'' because the frequency of the IgM deposition to the mesangium was high (Brack 1988(Brack , 1995Brack and Weber 1995). Also, it was reported that IgA was involved in this nephropathy (Brack et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Morphological Study of Progressive Glomerulonephropathy in Common Marmosets (Callithrix jacchus)

et al. 2013

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Spontaneous progressive glomerulonephropathy often occurs in common marmosets. However, there are few detailed reports concerning the agerelated progressive process of glomerular changes. We discuss the glomerular changes in the early stage and the progressive changes in the advanced stage of nephropathy. We investigated the kidneys of common marmosets (2-11 years old; 9 males and 12 females) using hematoxylin and eosin, periodic acid-Schiff, periodic acid-methenamine-silver, and Masson's trichrome (MT) stains and a transmission electron microscope. There was no remarkable change in urine cytology, hematology, or blood chemistry. In the early stage of nephropathy, effacement of podocyte foot processes was observed ultrastructurally even though there were no marked glomerular lesions in the light microscopy. Subsequently, mesangial proliferation occurred from the hilar to peripheral side along the tuft. In the middle stage, red deposits were visible at the glomerular basement membrane (GBM) and the mesangial region directly under the GBM (paramesangial area) with the MT stain. Electron dense deposits were seen at the same area. In the advanced stage, the irregularity became prominent with or without dense deposits. It is necessary to investigate in detail whether the change of podocyte in the early stage was immuno-mediated or due to podocyte failure.

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Ultrastructural and Histochemical Mesangial Alterations in Callitrichid IgM Nephropathy (Primates: Platyrrhina)

Cited by 16 publications

References 11 publications

Spontaneous Glomerular and Tubulointerstitial Lesions in Common Marmosets (Callithrix jacchus)

Spontaneous Glomerular and Tubulointerstitial Lesions in Common Marmosets (Callithrix jacchus)

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

Morphological Study of Progressive Glomerulonephropathy in Common Marmosets (Callithrix jacchus)

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