A comparative study of Merkel cell, BK and JC polyomavirus infections in renal transplant recipients and healthy subjects

Abstract

Background: Merkel cell carcinoma (MCC) is a rare skin cancer associated with immunosuppression and the integration of Merkel cell polyomavirus (MCPyV) DNA into the tumor cell genome. Little is known about the natural history of MCPyV infection.

Objectives: To investigate the presence of MCPyV, BK and JC polyomaviruses in serum and urine from immunosuppressed kidney transplant patients (KTx) and a control group of normal volunteers.

Study design: Quantitative real-time PCR (q-PCR) was used to assess MCPyV, BKV and JCV viral load in urine and serum samples collected from normal donors (Group A), prospectively enrolled KTx patients (Group B) and from KTx with documented BK reactivation and/or nephropathy (Group C).

Results: Low levels of MCPyV viruria was seen in 15% of the subjects in Group A, 30% of Group B, and was not detected in Group C. No individuals in the study developed MCPyV viremia. BK viruria was seen in 5% of Group A, 30% of Group B, and 100% of Group C. Consistent with previous reports, the mean BKV urinary load was significantly higher in immunosuppressed patients compared to non-immunosuppressed controls and also higher in urine compared to serum samples.

Conclusions: Like BKV and JCV, MCPyV is likely a common infection in adult humans. Low level shedding of MCPyV in urine was similar in immunosuppressed organ transplant recipients to non-immunosuppressed subjects. However, MCPyV was not detected and JCV was infrequent in samples from KTx patients with clinical BKV reactivation.

Fig. 1. BK, JC and MCPy viral loads in urine and serum of normal donors (Group A n=20) prospectively enrolled KTx (Group B n=20), and KTx enrolled on clinical BKV reactivation (Group C, n=5)

Shown are the viral loads in each patient group, with each point representing one measurement. The data include multiple samples at different time points for each patient in the two transplant groups for a total of 70 urine and 82 serum samples in Group B and 15 urine and 15 serum samples in Group C. One urine sample was examined from each of the donors in Group A. Viral loads in serum are shown as triangles, viral loads in urine are shown as diamond symbols. Black bars indicate the mean viral load in each group. Data are shown as viral copies per milliliter serum or urine. To avoid bias due to repeated measurements on the same subjects, mean gc/ml were calculated for the set of samples from each study subject and these values used for statistical comparison between groups. Mann-Whitney test was used for tests of significance. * indicates a P value of <0.05, ** P< 0.01.