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Journal of Clinical Microbiology, August 2009, p. 2577-2585, Vol. 47, No. 8
0095-1137/09/$08.00+0     doi:10.1128/JCM.00030-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Antibody Responses to Recombinant Polyomavirus BK Large T and VP1 Proteins in Young Kidney Transplant Patients{triangledown}

Sohrab Bodaghi,1 Patrizia Comoli,2 Robert Bösch,1 Alberta Azzi,3 Rainer Gosert,1 David Leuenberger,1 Fabrizio Ginevri,4 and Hans H. Hirsch1,5*

Transplantation Virology, Institute for Medical Microbiology, Department of Biomedicine, University of Basel, Basel, Switzerland,1 Pediatric Hematology/Oncology, IRCCS Policlinico S. Matteo, Pavia, Italy,2 Department of Public Health, University of Firenze, Florence, Italy,3 Pediatric Nephrology Unit, G. Gaslini Institute, Genoa, Italy,4 Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Basel, Switzerland5

Received 7 January 2009/ Returned for modification 1 May 2009/ Accepted 20 May 2009

BK virus (BKV)-specific immunity is critical for polyomavirus-associated nephropathy, but antibody responses are incompletely defined. We compared the hemagglutination inhibition assay (HIA) with immunoglobulin G enzyme immunoassays (EIA) to BKV proteins expressed in baculovirus-infected insect cells. N-terminal, internal, and C-terminal domains of the BKV large T antigen (BKLT) were fused to glutathione S-transferase (GST), yielding GST-BKLTD1, GST-BKLTD2, and GST-BKLTD3, respectively. The BKV capsid VP1 was expressed as a GST fusion (BKVP1) or as a native VP1 assembled into viruslike particles (BKVLP). We tested 422 sera from 28 healthy donors (HD), 99 dialysis patients (DP; median age, 15 years; range, 3 to 32 years), and 46 age-matched kidney transplant patients (KTP; median age, 15 years; range, 2 to 33 years). In HD, HIA and BKVLP EIA both yielded a 91.7% seroreactivity, whereas all other EIA responses were lower (BKVP1, 83.3%; BKLTD1, 25%; BKLTD2, 29%; BKLTD3, 40%). HIA titers significantly correlated with EIA levels for BKVLP, BKVP1, and BKLTD1 but not for BKLTD2 or BKLTD3, which were barely above the cutoff. In DP, the seroreactivities of HIA, BKVLP, and BKLTD1 were lower than that in HD (63.6%, 86.9%, and 10.1%, respectively) and they had lower titers (P < 0.001). In KTP, seropositivities for BKVLP, BKVP1, and BKLTD1 were 78%, 50%, and 17%, respectively, but anti-BKVLP levels increased significantly in KTP with viruria and viremia, whereas anti-BKLTD1 levels increased after clearing sustained BKV viremia. In conclusion, anti-BKVLP is equivalent to HIA in HD but is more sensitive to determine the BKV serostatus in DP and KTP. In KTP, anti-BKVLP responds to recent BKV viruria and viremia, whereas anti-BKLTD1 may indicate emerging BKV-specific immune control.


* Corresponding author. Mailing address: Transplantation Virology, Institute for Medical Microbiology, Department of Biomedicine, University of Basel, CH-4003 Basel, Switzerland. Phone: 41 61 267 3262. Fax: 41 61 267 3283. E-mail: hans.hirsch{at}unibas.ch

{triangledown} Published ahead of print on 27 May 2009.


Journal of Clinical Microbiology, August 2009, p. 2577-2585, Vol. 47, No. 8
0095-1137/09/$08.00+0     doi:10.1128/JCM.00030-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.