Introduction

BK polyomavirus (BKV) is a causative agent of BKV-associated nephropathy (BKVN) and hemorrhagic cystitis, which occur subsequent to the reactivation of BKV. Although the clinical implications of antibodies against BKV have not yet been clarified, intravenous immunoglobulin (IVIg), which is presumed to have significant neutralizing activity, may represent a promising approach for the control of BKV-associated diseases. The objective of this study was to measure anti-BKV antibody titer in an IVIg preparation as well as in renal transplant recipients and to examine its significance as a clinical marker.

Methods

Three IVIg products derived from donated blood samples in Japan as well as clinical samples from 45 recipients of kidney transplants at Akita University Hospital were used for evaluation of neutralizing titers and antibody titers. A reliable method of measurement using the human lung (carcinoma) cell line A549 and the Gardner strain of BKV was established to quantitatively determine neutralizing activity. Antibody titers in the samples were evaluated by neutralizing capacity and binding capacity, using enzyme-linked immunosorbent assays.

Results

The mean neutralizing titer against BKV was 2,687-fold (±558) higher in pooled plasma and 12,014-fold (±2,145) higher in IVIg products concentrated from pooled plasma. Stable high antibody titers of all IVIgs were found against BKV subtype I/c, which is the major subtype in Japan. In contrast, the antibody titers among the renal transplant recipients differed, and recipients who had BKVN showed a particular tendency to have low antibody titers before surgery.

Conclusions

IVIg products derived from more than 10,000 lots of plasma exhibited significant neutralizing activity against BKV, and the neutralizing titers were stable for more than 10 years without appreciable change. Anti-BKV antibody titers of kidney transplant recipients might be a useful clinical marker for a potential risk of BKVN.

Funding

None