Pretransplant BKV-IgG serostatus and BKV-specific ELISPOT assays to predict BKV infection after kidney transplantation

Hyunjoo Bae; Seungwon Jung; Byung Ha Chung; Chul Woo Yang; Eun-Jee Oh

doi:10.3389/fimmu.2023.1243912

Pretransplant BKV-IgG serostatus and BKV-specific ELISPOT assays to predict BKV infection after kidney transplantation

Front Immunol. 2023 Sep 21:14:1243912. doi: 10.3389/fimmu.2023.1243912. eCollection 2023.

Authors

Hyunjoo Bae¹, Seungwon Jung², Byung Ha Chung³, Chul Woo Yang³, Eun-Jee Oh^{4

5}

Affiliations

¹ Department of Biomedicine & Health Sciences, Graduate School, The Catholic University of Korea, Seoul, Republic of Korea.
² Department of Laboratory Medicine, Uijeongbu Paik Hospital, Uijeongbu, Republic of Korea.
³ Division of Nephrology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
⁴ Resesarch and Development Institute for In Vitro Diagnostic Medical Devices, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
⁵ Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Abstract

Introduction: Polyomavirus (BKV) infection can lead to major complications and damage to the graft in kidney transplant recipients (KTRs). We investigated whether pretransplant BK serostatus and BK-specific cell-mediated immunity (CMI) predicts post-transplant BK infection.

Methods: A total of 93 donor-recipient pairs who underwent kidney transplantation (KT) and 44 healthy controls were examined. Assessment of donor and recipient BKV serostatus and BKV-CMI in recipients was performed prior to transplantation using BKV-IgG ELISA and BKV-specific IFN-g ELISPOT assays against five BK viral antigens (LT, St, VP1, VP2, and VP3). BK viremia was diagnosed when blood BKV-DNA of 104 copies/mL or more was detected during follow-up periods.

Results: Anti-BKV IgG antibody was detected in 74 (79.6%) of 93 KTRs and in 68 (73.1%) of 93 KT donors. A greater percentage of KTRs who received allograft from donors with high levels of anti-BKV IgG had posttransplant BK viremia (+) than KTRs from donors with low anti-BKV IgG (25.5% [12/47] vs. 4.3% [2/46], respectively; P = 0.007). Pretransplant total BKV-ELISPOT results were lower in BK viremia (+) patients than in patients without viremia (-) 20.5 [range 9.9-63.6] vs. 72.0 [43.2 - 110.8]; P = 0. 027). The sensitivity and specificity of the total BKV-ELISPOT assay (cut-off ≤ 53 spots/3×105 cells) for prediction of posttransplant BK viremia were 71.4 (95% CI: 41.9-91.6) and 54.4 (42.8-65.7), respectively. The combination of high donor BKV-IgG, low recipient BKV-IgG, and low total BKV-ELISPOT results improved specificity to 91.1%.

Discussion: Our study highlights the importance of pretransplant BKV-IgG serostatus and BKV-specific CMI in predicting posttransplant BKV infection in KTRs. The combination of high donor BKV-IgG, low recipient BKV-IgG, and low total BKV-ELISPOT results predicted BK viremia after KT. Pretransplant identification of patients at highrisk for BK viremia could enable timely interventions and improve clinical outcomes of KTRs.

Keywords: BK polyomavirus; BK viremia; BKV-specific ELISPOT; kidney transplant recipients; pre-transplant BKV-IgG serostatus.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

BK Virus* / genetics
Enzyme-Linked Immunospot Assay
Humans
Immunoglobulin G
Kidney Transplantation* / adverse effects
Polyomavirus Infections*
Tumor Virus Infections*
Viremia

Substances

Immunoglobulin G

Grants and funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2020R1A2B5B01001859), Republic of Korea. This work was also supported by the Institute of Civil Military Technology Cooperation funded by the Defense Acquisition Program Administration and Ministry of Trade, Industry and Energy of Korean government under grant No. 22-CM-EC-18.