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Comparison of Immunohistochemical Staining for Large T Antigen and Capsid Protein VP1 in BK Polyomavirus-Associated Nephropathy. | LitMetric

AI Article Synopsis

  • The study investigates the role of VP1 capsid protein expression in BK polyomavirus-associated nephropathy (BKPyVAN), comparing it to the commonly used SV40 large T antigen (TAg) staining for diagnosis.
  • Immunohistochemical analysis on biopsy samples revealed VP1 positivity in various cellular locations, but it appeared in fewer tubules compared to TAg, suggesting possible underdiagnosis in cases with minimal viral replication.
  • A significant correlation was found between the percentage of VP1-positive tubules and increased serum creatinine levels, indicating that higher VP1 expression may signal advanced tubular damage and potential graft dysfunction.

Article Abstract

Aim: Most transplant centres use SV40 large T antigen (TAg) staining for the diagnosis and assessment of BK polyomavirus-associated nephropathy (BKPyVAN). This study was performed to evaluate the significance of capsid protein VP1 expression in BKPyVAN.

Methods: We performed immunohistochemical staining using anti-SV40 TAg and anti-BKPyV VP1 antibodies in 16 index biopsies and 12 re-biopsies of BKPyVAN and compared the patterns of positivity and the percentage of positive tubules by counting whole specimens. We investigated the correlation between serum creatinine increase from baseline and the percentage of positive tubules for both markers in 16 index biopsies.

Results: In VP1 staining, positive findings were observed not only in the nuclei of tubular epithelial cells but also in the cytoplasm, cells shedding into the lumen, intra-tubular casts, and in the interstitium. Two of 28 biopsies (7.1%) showed TAg-positive and VP1-negative results, in which TAg-positive cells were detected only in a single tubule. The median (interquartile range) percentage of positive tubules was 2.8% (0.7-9.8%) for TAg and 1.4% (0.5-3.9%) for VP1 staining (p = 0.2). In 16 index biopsies, serum creatinine increases significantly correlated with the percentage of VP1-positive tubules (r = 0.49, p = 0.02), while this correlation revealed borderline significance with TAg-positive tubules.

Conclusions: VP1 expression showed various patterns, but was detected in half as many tubules as TAg staining, which might lead to false negatives in the samples with minimal viral replication. However, increased VP1-positive tubules indicate advanced tubular damage and possible association with graft dysfunction.

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Source
http://dx.doi.org/10.1159/000510967DOI Listing

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