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Clinical and Vaccine Immunology, October 2008, p. 1564-1571, Vol. 15, No. 10
1071-412X/08/$08.00+0     doi:10.1128/CVI.00206-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Longitudinal Analysis of Levels of Immunoglobulins against BK Virus Capsid Proteins in Kidney Transplant Recipients{triangledown}

P. Randhawa,1* D. Bohl,2 D. Brennan,2 K. Ruppert,1 B. Ramaswami,1 G. Storch,2 J. March,1 R. Shapiro,4 and R. Viscidi3

Diabetes Research Institute and Departments of Pathology,1 Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania,4 Department of Medicine, Washington University at St. Louis, St. Louis, Missouri,2 Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland3

Received 28 May 2008/ Returned for modification 11 July 2008/ Accepted 15 August 2008

This study sought to evaluate serology and PCR as tools for measuring BK virus (BKV) replication. Levels of immunoglobulin G (IgG), IgM, and IgA against BKV capsids were measured at five time points for 535 serial samples from 107 patients by using a virus-like particle-based enzyme-linked immunosorbent assay. Viral DNA in urine and plasma samples was quantitated. The seroconversion rate was 87.5% (14/16); 78.6% (11/14) and 14.3% (2/14) of patients who seroconverted developed viruria and viremia, respectively. Transient seroreversion was observed in 18.7% of patients at 17.4 ± 11.9 weeks posttransplant and was not attributable to loss of antigenic stimulation, changes in immunosuppression, or antiviral treatment. Titers for anti-BK IgG, IgA, and IgM were higher in patients with BKV replication than in those without BKV replication. A rise in the optical density (OD) of anti-BK IgA (0.19), IgM (0.04), or IgG (0.38) had a sensitivity of 76.6 to 88.0% and a specificity of 71.7 to 76.1% for detection of viruria. An anti-BK IgG- and IgA-positive phenotype at week 1 was less frequent in patients who subsequently developed viremia (14.3%) than in those who subsequently developed viruria (42.2%) (P = 0.04). Anti-BK IgG OD at week 1 showed a weak negative correlation with peak urine viral load (r = –0.25; P = 0.05). In summary, serial measurements of anti-BKV immunoglobulin class (i) detect onset of viral replication, (ii) document episodes of seroreversion, and (iii) can potentially provide prognostic information.


* Corresponding author. Mailing address: Department of Pathology, Division of Transplant Pathology, University of Pittsburgh, E737 UPMC-Montefiore Hospital, 3459 Fifth Ave., Pittsburgh, PA 15213. Phone: (412) 647-7646. Fax: (412) 647-5237. E-mail: randhawapa{at}msx.upmc.edu

{triangledown} Published ahead of print on 27 August 2008.


Clinical and Vaccine Immunology, October 2008, p. 1564-1571, Vol. 15, No. 10
1071-412X/08/$08.00+0     doi:10.1128/CVI.00206-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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