Immunoglobulin G, A, and M Responses to BK Virus in Renal Transplantation

Randhawa, Parmjeet; Gupta, Gaurav; Vats, Abhay; Shapiro, Ron; Viscidi, Raphael P.

doi:10.1128/cvi.00114-06

Cited by 53 publications

(45 citation statements)

References 50 publications

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“…Anti-agnoprotein IgG was detected in only 15% and 7.5% of HD and KT patients, respectively, which was significantly lower than the 63% and 80% seropositivity for VP1 and the 42% and 62% seropositivity for LTD1, respectively. In adult populations similar to our study groups, BKV seroprevalence rates of between 60 and 90% have been reported using assays which detect antibody responses directed against the major capsid protein VP1 by EIA or by inhibiting its interaction with receptor-like glycosylated surface structures of type O erythrocytes, i.e., by hemagglutination inhibition (18,23,25,32). The higher VP1-type response may partly be due to the fact that the host immune system is more readily and even systemically (re)exposed to viral surface proteins which typically contain neutralizing epitopes (11).…”

Section: Discussionsupporting

confidence: 80%

Human Polyomavirus Type 1 (BK Virus) Agnoprotein Is Abundantly Expressed but Immunologically Ignored

Leuenberger

Andresen

Gosert

et al. 2007

Clin Vaccine Immunol

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Impaired BK virus (BKV)-specific immunity is a key risk factor of polyomavirus-associated nephropathy. We hypothesized that BKV agnoprotein might constitute an important immune target, as it is highly expressed after infection in vitro. We demonstrate abundant expression of BKV agnoprotein in vivo by immunostaining of kidney transplant (KT) biopsy specimens. Antibody responses to the recombinant affinity-purified BKV agnoprotein, large tumor (LT), and VP1 antigens in 146 sera from 38 KT patients and in 19 sera from 16 healthy donors (HD) were compared by enzyme immunoassay. In HD, low titers of anti-agnoprotein immunoglobulin G (IgG) were found in 15% of sera, compared to 41% for anti-LT antigen and 63% for anti-VP1. No anti-BKV IgM was detectable. In KT patients, anti-agnoprotein IgG and IgM were found in 8% and 3.6% of sera, compared to 63% and 18% for anti-LT IgG and IgM and 80% and 41% for anti-VP1 IgG and IgM, respectively. Anti-LT antigen and anti-VP1, but not anti-agnoprotein, activities increased during and after BKV viremia in KT patients. To investigate specific cellular immune responses, we compared levels of gamma interferon production in peripheral blood mononuclear cells (PBMC) of 10 HD and 30 KT patients by enzyme-linked immunospot assay. In HD, the median numbers of gamma interferon spot-forming units per million PBMC for the agnoprotein, LT antigen, and VP1 peptides were 1, 23, and 25, respectively, whereas the responses in KT patients were 2, 24, and 99, respectively. We conclude that BKV agnoprotein, though abundantly expressed in vivo, is poorly recognized immunologically.The human polyomavirus BK virus (BKV) is the primary etiological agent of polyomavirus-associated nephropathy (PVAN), which causes irreversible graft loss in 1 to 10% of kidney transplant (KT) patients (15, 31). BKV was first discovered in 1970 in the urine of a KT patient with the initials B.K. who had ureteric stenosis and abundant decoy cell shedding (9). However, BKV asymptomatically infects 60 to 90% of the human population (23) and establishes a state of nonreplicative infection in the renourinary tract (13, 15). Intermittent low-level urinary replication with BKV loads of Յ10e6 per ml is detected in 5% of immunocompetent individuals, whereas high-level replication with BKV loads of Ն10e7 per ml is found in 20 to 60% of immunosuppressed patients (15). In KT patients, high-level urine BKV replication is found in 30%, which may be followed by BKV viremia in 13% and by histologically confirmed PVAN in 8% of patients (18). The risk factors for PVAN are not conclusively defined and likely involve complementing determinants of the triad of recipient, graft, and virus (17). Disruption of the balance between the BKV replication and host immune control is generally viewed as a key element of PVAN pathogenesis (5). In the absence of validated antivirals, reducing maintenance immunosuppression represents the primary treatment option for presumptive or definitive PVAN (3,39).BKV belongs to the genus Polyomavirus of the Polyomavir...

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Section: Discussionsupporting

confidence: 80%

Human Polyomavirus Type 1 (BK Virus) Agnoprotein Is Abundantly Expressed but Immunologically Ignored

Leuenberger

Andresen

Gosert

et al. 2007

Clin Vaccine Immunol

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“…All have reported marked increases in anti-BK IgG antibody titer under conditions associated with viral replication (viruria, viremia, or nephropathy). Elevation of anti-BK IgA and anti-BK IgM class antibodies in the same clinical setting has been reported in a retrospective cross-sectional study of kidney transplant patients at the University of Pittsburgh (42). The current study examined antibody class and OD in a prospectively collected set of samples.…”

Section: Discussionmentioning

confidence: 57%

“…For this study, BKV-specific antibodies in plasma samples were measured using a VLP-based ELISA (42). This assay does not show cross-reactivity with anti-JC virus antibodies.…”

Section: Methodsmentioning

confidence: 99%

“…Immunoglobulin classes were usually not measured, and the patients studied were not well characterized from a clinical perspective. Several recent studies have used enzyme-linked immunosorbent assay (ELISA) technology and have shown marked elevations in anti-BKV antibodies in patients with active viral replication (4,22,23,31,42). It has been difficult to show definitively whether this intense humoral immune response actually contributes to resolution of viral nephropathy.…”

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confidence: 99%

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

Randhawa

Bohl

Brennan

et al. 2008

Clin Vaccine Immunol

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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.

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“…For 7 cases, either a second-matched control could not be identified or a serum sample from the control was not available. These 239 samples were tested for BKV and JCV seroreactivity using VLP EIA at 1:200 and 1:100 dilutions, respectively as described previously (6,(23)(24)(25). COVs used for BKV and JCV were an OD > 0.200 and OD > 0.150, respectively and were determined following the same methodology described above for the MCV EIA.…”

Section: Further Exploratory Subsample Analysismentioning

confidence: 99%

Antibody Response to Merkel Cell Polyomavirus Associated with Incident Lymphoma in the Epilymph Case–Control Study in Spain

Robles

Poloczek

Casabonne

et al. 2012

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Merkel cell polyomavirus (MCV) has been identified as the cause of Merkel cell carcinoma. The increased incidence of chronic lymphocytic leukemia in Merkel cell cancer cohorts and the lymphotropic properties of the virus suggest a possible viral association with lymphomagenesis. To investigate this potential role, we explored seroreactivity against MCV VP1 capsids within the Epilymph case-control study in Spain.Methods: Serum samples from 468 incident lymphomas, categorized into up to 11 entities, and 522 controls frequency matched by age, sex, and recruitment center were tested for MCV antibodies by enzyme immunoassay using Virus-Like-Particles. Adjusted multinomial logistic regression was used to estimate the OR and 95% confidence interval (CI) associated to MCV seroprevalence. Immunosuppressed subjects were excluded.Results: MCV seroprevalence was 82% in controls and 85% in lymphoma cases. Among 11 lymphoma categories, MCV seropositivity was significantly higher in diffuse large B-cell lymphomas (DLBCL; 96.4%; OR ¼ 6.1, 95%CI ¼ 1.9-19.8), as compared with controls. MCV prevalences were also higher in follicular lymphoma, lymphoplasmacytic lymphoma, chronic lymphocytic leukemia, Hodgkin lymphoma, and mature T-cell lymphoma but differences did not reach statistical significance. Lower prevalences were observed for multiple myeloma and other B-cell lymphoma. Exclusion of samples collected after start of treatment did not change the results. In a subset analysis, no significant association was observed between BKV and JCV seroprevalence and DLBCL.Conclusion: The association observed between serologic evidence of MCV exposure and DLBCL warrants further research. Impact: MCV might be involved in the pathway of DLBCL and other lymphomas. Cancer Epidemiol Biomarkers Prev; 21(9); 1592-8. Ó2012 AACR.

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Immunoglobulin G, A, and M Responses to BK Virus in Renal Transplantation

Cited by 53 publications

References 50 publications

Human Polyomavirus Type 1 (BK Virus) Agnoprotein Is Abundantly Expressed but Immunologically Ignored

Human Polyomavirus Type 1 (BK Virus) Agnoprotein Is Abundantly Expressed but Immunologically Ignored

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

Antibody Response to Merkel Cell Polyomavirus Associated with Incident Lymphoma in the Epilymph Case–Control Study in Spain

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