Apolipoprotein E Immunostaining Has Diagnostic Utility in Differentiating Dense Deposit Disease and C3
Ozge Hurdogan1, Safak Mirioglu2, Ahmet Burak Dirim3
1Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Abstract:
Electron microscopy (EM) has been essential for the diagnosis of dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). Recent research showed significantly higher accumulation of apolipoprotein E (ApoE) in DDD compared with C3GN and tested the use of ApoE immunohistochemistry for DDD diagnosis. We aimed to investigate the diagnostic value of ApoE in DDD and C3GN using 3 distinct ApoE clones-D719N, EP1373Y, and 1B2C9. Kidney biopsies of 26 DDD and 18 C3GN, diagnosed based on EM findings, were subjected to immunohistochemical analyses using ApoE clones D719N, EP1373Y, and 1B2C9. Kidney biopsies of 8 immune complex-mediated membranoproliferative glomerulonephritis, 13 acute postinfectious glomerulonephritis, 13 focal segmental glomerulosclerosis, 6 minimal change disease, 13 membranous nephropathy, 11 lupus nephritis, and 9 fibrillary glomerulonephritis constituted the control group. The staining pattern, intensity, and distribution were evaluated in each renal compartment. Linear/predominantly linear staining of score 2 to 3 intensity in a diffuse/global distribution was interpreted as diagnostic for DDD. DDD and C3GN cases were reclassified using each clone individually. D719N confirmed the diagnosis of DDD in 76.9% of the cases, whereas EP1373Y and 1B2C9 in 84.6%. All 3 clones confirmed C3GN diagnosis in 94.4% of the cases. EP1373Y and 1B2C9 demonstrated superior sensitivity (85% vs 77%) and overall diagnostic accuracy compared with D719N (89% vs 85%). Clone 1B2C9 showed significantly more intense background staining compared with D719N and EP1373Y in all cases (P < .001). No cases in the control group showed false-positive staining, except for 66.7% of fibrillary glomerulonephritis. Notably, 2 among 6 D719N-negative DDDs were transplant biopsies, and 2 belonged to the same patient with Barraquer-Simons syndrome. All 3 ApoE clones, D719N, EP1373Y, and 1B2C9, can be used for routine diagnosis in the absence of EM or as an adjunct to EM to increase diagnostic accuracy in differentiating DDD and C3GN.
