German Shorthaired Pointer dogs with exfoliative cutaneous lupus erythematosus develop immune-complex membranous glomerulonephropathy

Abstract

German Shorthaired Pointer (GSHP) dogs with a UNC93B1 gene mutation develop exfoliative cutaneous lupus erythematosus (ECLE) and kidney disease resembling lupus nephritis in humans. The objective of this study was to characterize the kidney disease by light microscopy, immunofluorescence, and electron microscopy in a population of GSHP dogs with ECLE. Medical records were reviewed, and light microscopy of kidneys from 7 GSHP dogs with a previous histologic diagnosis of ECLE was performed. Immunofluorescence of fresh-frozen kidney from 1 dog and transmission electron microscopy of kidney from that dog and 2 additional dogs were performed. Five of 7 dogs had proteinuria diagnosed by urinalysis or urine protein-to-creatinine ratio. Two of 7 dogs were intermittently hypoalbuminemic, and none were azotemic. Histologic findings included early (2 dogs) to late (5 dogs) membranous glomerulonephropathy characterized by mild-to-severe glomerular capillary loop thickening and tubular proteinosis. In all 7 cases, trichrome staining revealed red granular immune deposits on the subepithelial surface of the glomerular basement membrane. Immunofluorescence revealed strong granular labeling for immunoglobulins and complement protein C3. Electron microscopy demonstrated subepithelial electron-dense immune deposits encircled by the remodeled glomerular basement membrane. These findings are diagnostic of immune-complex membranous glomerulonephropathy and are similar to class V lupus in humans. This cohort of GSHP dogs with ECLE developed immune-complex membranous glomerulonephropathy, which we hypothesize is a manifestation of systemic lupus erythematosus. GSHP dogs with ECLE should undergo clinical evaluation of renal function for early identification and treatment.

Keywords: canine; cutaneous lupus erythematosus; glomerular disease; immune-complex glomerulopathy; proteinuria; renal biopsy.

Figure 1.

Histologic lesions in the skin and kidney of German Shorthair Pointer (GSHP) dogs with exfoliative cutaneous lupus erythematosus. (a) Exfoliative cutaneous lupus erythematosus, haired skin, 10-month-old GSHP dog. The epidermal changes are characterized by lymphocytic interface dermatitis with basal layer vacuolar change, pigmentary incontinence, and orthokeratotic hyperkeratosis. Hematoxylin and eosin (HE). (b–d) Late membranous glomerulonephropathy, kidney, dog. (b, c) Glomeruli are characterized by global diffuse capillary loop thickening (arrows), mild mesangial hypercellularity, Bowman’s capsule thickening, and synechia. HE (b) and period acid-Schiff (c). (d) Numerous small red granular immune deposits are on the external (subepithelial) surface of the glomerular basement membrane (arrows). Masson’s trichrome.

Figure 2.

Late membranous glomerulonephropathy, kidney, dog. (a) Strong, granular IgG labeling is observed along glomerular basement membranes. IgG immunofluorescence. (b) Multiple electron-dense deposits are in the subepithelial zones of capillary loops and are encircled by new basement membrane material (solid arrows). Some have evidence of resorption with a mottled appearance (empty arrow). Transmission electron microscopy, scale bar = 1 μm.