{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:31:26Z","timestamp":1772253086619,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:00:00Z","timestamp":1634860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>BK polyomavirus (BKPyV) persists lifelong in renal and urothelial cells with asymptomatic urinary shedding in healthy individuals. In some immunocompromised persons after transplantation of hematopoietic stem cells (HSCT), the BKPyV high-rate replication is associated with haemorrhagic cystitis (HC). We tested whether the status of BKPyV immunity prior to HSCT could provide evidence for the BKPyV tendency to reactivate. We have shown that measurement of pretransplant anti-BKPyV 1 and 4 IgG levels can be used to evaluate the HC risk. Patients with anti-BKPyV IgG in the range of the 1st\u20132nd quartile of positive values and with positive clinical risk markers have a significantly increased HC risk, in comparison to the reference group of patients with \u201cnon-reactive\u201d anti-BKPyV IgG levels and with low clinical risk (LCR) (p = 0.0009). The predictive value of pretransplant BKPyV-specific IgG was confirmed by determination of genotypes of the shed virus. A positive predictive value was also found for pretransplant T-cell immunity to the BKPyV antigen VP1 because the magnitude of IFN-\u03b3 T-cell response inversely correlated with posttransplant DNAuria and with HC. Our novel data suggest that specific T-cells control BKPyV latency before HSCT, and in this way may influence BKPyV reactivation after HSCT. Our study has shown that prediction using a combination of clinical and immunological pretransplant risk factors can help early identification of HSCT recipients at high risk of BKPyV disease.<\/jats:p>","DOI":"10.3390\/vaccines9111226","type":"journal-article","created":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T21:42:05Z","timestamp":1635198125000},"page":"1226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pretransplant BK Virus-Specific T-Cell-Mediated Immunity and Serotype Specific Antibodies May Have Utility in Identifying Patients at Risk of BK Virus-Associated Haemorrhagic Cystitis after Allogeneic HSCT"],"prefix":"10.3390","volume":"9","author":[{"given":"Mark\u00e9ta","family":"\u0160\u0165astn\u00e1-Markov\u00e1","sequence":"first","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, 128 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Ham\u0161\u00edkov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, 128 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr","family":"Hainz","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, 128 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petr","family":"Hub\u00e1\u010dek","sequence":"additional","affiliation":[{"name":"Laboratory of Virology, Motol Hospital, 150 06 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Kroutilov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, 128 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jitka","family":"Kry\u0161tofov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, 128 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viera","family":"Ludv\u00edkov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, 128 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Musil","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, 128 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavla","family":"Pecherkov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, 128 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Sal\u00e1kov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, 128 20 Prague, Czech Republic"},{"name":"Department of Genetics and Microbiology, Faculty of Science, Charles University, 120 00 Prague, Czech Republic"},{"name":"BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences, Charles University, 252 50 Vestec, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vojt\u011bch","family":"\u0160roller","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, 128 20 Prague, Czech Republic"},{"name":"Department of Genetics and Microbiology, Faculty of Science, Charles University, 120 00 Prague, Czech Republic"},{"name":"BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences, Charles University, 252 50 Vestec, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Vydra","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, 128 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6001-4007","authenticated-orcid":false,"given":"\u0160\u00e1rka","family":"N\u011bme\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Haematology and Blood Transfusion, 128 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104150","DOI":"10.1016\/j.meegid.2019.104150","article-title":"Evolution and molecular epidemiology of polyomaviruses","volume":"79","author":"Torres","year":"2020","journal-title":"Infect. Genet. Evol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.meegid.2008.05.006","article-title":"Evolution of four BK virus subtypes","volume":"8","author":"Krumbholz","year":"2008","journal-title":"Infect. Genet. Evol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1099\/vir.0.18842-0","article-title":"Seroepidemiology of the human polyomaviruses","volume":"84","author":"Stolt","year":"2003","journal-title":"J. Gen. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kean, J.M., Rao, S., Wang, M., and Garcea, R.L. (2009). Seroepidemiology of human polyomaviruses. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000363"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jcv.2018.11.009","article-title":"Development and evaluation of a BK polyomavirus serotyping assay using Luminex technology","volume":"110","author":"Wunderink","year":"2019","journal-title":"J. Clin. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1002\/jmv.23841","article-title":"Seroprevalence rates of BKV, JCV, and MCPyV polyomaviruses in the general Czech Republic population","volume":"86","author":"Sroller","year":"2014","journal-title":"J. Med. Virol."},{"key":"ref_7","first-page":"12","article-title":"ECIL guidelines for the prevention, diagnosis and treatment of BK polyomavirus-associated haemorrhagic cystitis in haematopoietic stem cell transplant recipients","volume":"73","author":"Cesaro","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1038\/bmt.2015.162","article-title":"Hemorrhagic cystitis after allogeneic hematopoietic cell transplantation: Risk factors, graft source and survival","volume":"50","author":"Lunde","year":"2015","journal-title":"Bone Marrow Transplant."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.bbmt.2005.06.007","article-title":"Incidence, clinical outcome, and management of virus-induced hemorrhagic cystitis in children and adolescents after allogeneic hematopoietic cell transplantation","volume":"11","author":"Gorczynska","year":"2005","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/sj.bmt.1705909","article-title":"A prospective study of BK-virus-associated haemorrhagic cystitis in paediatric patients undergoing allogeneic haematopoietic stem cell transplantation","volume":"41","author":"Cesaro","year":"2008","journal-title":"Bone Marrow Transplant."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1182\/blood.V98.6.1971","article-title":"Quantification of polyoma BK viruria in hemorrhagic cystitis complicating bone marrow transplantation","volume":"98","author":"Leung","year":"2001","journal-title":"Blood"},{"key":"ref_12","first-page":"401","article-title":"The incidence of hemorrhagic cystitis and BK-viruria in allogeneic hematopoietic stem cell recipients according to intensity of the conditioning regimen","volume":"91","author":"Giraud","year":"2006","journal-title":"Haematologica"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1111\/j.1399-0012.2007.00705.x","article-title":"Hemorrhagic cystitis: A retrospective single-center survey","volume":"21","author":"Hassan","year":"2007","journal-title":"Clin. Transplant."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1179\/1607845412Y.0000000010","article-title":"Risk factors for and prognosis of hemorrhagic cystitis after allogeneic stem cell transplantation: Retrospective analysis in a single institution","volume":"17","author":"Arai","year":"2012","journal-title":"Hematology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/joim.12056","article-title":"A prospective randomized toxicity study to compare reduced-intensity and myeloablative conditioning in patients with myeloid leukaemia undergoing allogeneic haematopoietic stem cell transplantation","volume":"274","author":"Ringden","year":"2013","journal-title":"J. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1038\/bmt.2014.181","article-title":"The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and severe acute GVHD","volume":"49","author":"Uhm","year":"2014","journal-title":"Bone Marrow Transplant."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3547","DOI":"10.1200\/JCO.2017.73.0655","article-title":"Off-the-Shelf Virus-Specific T Cells to Treat BK Virus, Human Herpesvirus 6, Cytomegalovirus, Epstein-Barr Virus, and Adenovirus Infections After Allogeneic Hematopoietic Stem-Cell Transplantation","volume":"35","author":"Tzannou","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1111\/ejh.12848","article-title":"BKV-specific T cells in the treatment of severe refractory haemorrhagic cystitis after HLA-haploidentical haematopoietic cell transplantation","volume":"98","author":"Pello","year":"2017","journal-title":"Eur. J. Haematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1681\/ASN.2017050532","article-title":"Neutralizing Antibody-Mediated Response and Risk of BK Virus-Associated Nephropathy","volume":"29","author":"Solis","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1056\/NEJM198607243150405","article-title":"Association of BK viruria with hemorrhagic cystitis in recipients of bone marrow transplants","volume":"315","author":"Arthur","year":"1986","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1086\/511863","article-title":"Relationship of pretransplantation polyoma BK virus serologic findings and BK viral reactivation after hematopoietic stem cell transplantation","volume":"44","author":"Wong","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/j.bbmt.2014.04.017","article-title":"Relationship of BK polyoma virus (BKV) in the urine with hemorrhagic cystitis and renal function in recipients of T Cell-depleted peripheral blood and cord blood stem cell transplantations","volume":"20","author":"Lee","year":"2014","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1002\/pbc.25536","article-title":"Antibodies to BK virus in children prior to allogeneic hematopoietic cell transplant","volume":"62","author":"Laskin","year":"2015","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1002\/jmv.1890230405","article-title":"BK virus specific humoral and cell mediated immunity in allogeneic bone marrow transplant (BMT) recipients","volume":"23","author":"Drummond","year":"1987","journal-title":"J. Med. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.3109\/10428191003746323","article-title":"Polyomavirus BK-specific CD8+ T cell responses in patients after allogeneic stem cell transplant","volume":"51","author":"Schneidawind","year":"2010","journal-title":"Leuk. Lymphoma"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0166-0934(01)00447-5","article-title":"Real-time quantitative analysis of polyoma BK viremia and viruria in renal allograft recipients","volume":"103","author":"Leung","year":"2002","journal-title":"J. Virol. Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jcv.2004.12.018","article-title":"Specific and quantitative detection of human polyomaviruses BKV, JCV, and SV40 by real time PCR","volume":"34","author":"McNees","year":"2005","journal-title":"J. Clin. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1002\/jmv.24440","article-title":"Seroprevalence rates of HPyV6, HPyV7, TSPyV, HPyV9, MWPyV and KIPyV polyomaviruses among the healthy blood donors","volume":"88","author":"Sroller","year":"2016","journal-title":"J. Med. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hrbacek, J., Urban, M., Hamsikova, E., Tachezy, R., Eis, V., Brabec, M., and Heracek, J. (2011). Serum antibodies against genitourinary infectious agents in prostate cancer and benign prostate hyperplasia patients: A case-control study. BMC Cancer, 11.","DOI":"10.1186\/1471-2407-11-53"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1128\/JCM.01180-16","article-title":"A Simple and Reliable Strategy for BK Virus Subtyping and Subgrouping","volume":"55","author":"Morel","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1179\/102453311X13025568941763","article-title":"Clinical profile and outcome of urotheliotropic viral haemorrhagic cystitis following haematopoietic stem cell transplantation: A 7-year tertiary centre analysis","volume":"16","author":"Anoop","year":"2011","journal-title":"Hematology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5394","DOI":"10.1128\/JCM.42.11.5394-5396.2004","article-title":"Association between a high BK virus load in urine samples of patients with graft-versus-host disease and development of hemorrhagic cystitis after hematopoietic stem cell transplantation","volume":"42","author":"Bogdanovic","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4674","DOI":"10.1182\/blood-2003-08-2815","article-title":"Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: Donor type matters","volume":"103","author":"Saliba","year":"2004","journal-title":"Blood"},{"key":"ref_34","first-page":"939","article-title":"Full myeloablative conditioning and an unrelated HLA mismatched donor increase the risk for BK virus-positive hemorrhagic cystitis in allogeneic hematopoetic stem cell transplanted patients","volume":"31","author":"Dalianis","year":"2011","journal-title":"Anticancer Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.bbmt.2014.01.014","article-title":"BK virus disease after allogeneic stem cell transplantation: A cohort analysis","volume":"20","author":"Rorije","year":"2014","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/j.bbmt.2020.01.013","article-title":"Infections after Allogenic Transplant with Post-Transplant Cyclophosphamide: Impact of Donor HLA Matching","volume":"26","author":"Oltolini","year":"2020","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.3324\/haematol.2009.016758","article-title":"Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type","volume":"95","author":"Patah","year":"2010","journal-title":"Haematologica"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/sj.bmt.1701523","article-title":"Risk factors for severe hemorrhagic cystitis following BMT","volume":"23","author":"Seber","year":"1999","journal-title":"Bone Marrow Transplant."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/sj.bmt.1704261","article-title":"Late hemorrhagic cystitis after reduced-intensity hematopoietic stem cell transplantation (RIST)","volume":"32","author":"Yamamoto","year":"2003","journal-title":"Bone Marrow Transplant."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.jcv.2007.12.001","article-title":"Monitoring human cytomegalovirus infection in transplant recipients","volume":"41","author":"Baldanti","year":"2008","journal-title":"J. Clin. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/jmv.21727","article-title":"Ex vivo monitoring of human cytomegalovirus-specific CD8(+) T-Cell responses using the QuantiFERON-CMV assay in allogeneic hematopoietic stem cell transplant recipients attending an Irish hospital","volume":"82","author":"Fleming","year":"2010","journal-title":"J. Med. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1038\/s41409-018-0402-3","article-title":"Donor lymphocyte infusion for BK virus hemorrhagic cystitis and nephropathy: A case report","volume":"54","author":"Orti","year":"2019","journal-title":"Bone Marrow Transplant."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3495","DOI":"10.1128\/JVI.80.7.3495-3505.2006","article-title":"Interplay of cellular and humoral immune responses against BK virus in kidney transplant recipients with polyomavirus nephropathy","volume":"80","author":"Chen","year":"2006","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1111\/j.1600-6143.2011.03693.x","article-title":"BK virus-specific immunity kinetics: A predictor of recovery from polyomavirus BK-associated nephropathy","volume":"11","author":"Schachtner","year":"2011","journal-title":"Am. J. Transplant"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1111\/ajt.13252","article-title":"The Loss of BKV-specific Immunity from Pretransplantation to Posttransplantation Identifies Kidney Transplant Recipients at Increased Risk of BKV Replication","volume":"15","author":"Schachtner","year":"2015","journal-title":"Am. J. Transplant"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.ccell.2014.10.018","article-title":"The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function","volume":"26","author":"Johnston","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nature04444","article-title":"Restoring function in exhausted CD8 T cells during chronic viral infection","volume":"439","author":"Barber","year":"2006","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3642","DOI":"10.4049\/jimmunol.1003292","article-title":"Highly activated cytotoxic CD8 T cells express protective IL-10 at the peak of coronavirus-induced encephalitis","volume":"186","author":"Trandem","year":"2011","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/nm.1929","article-title":"Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10","volume":"15","author":"Sun","year":"2009","journal-title":"Nat. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3611","DOI":"10.1038\/s41388-020-1239-y","article-title":"Alterations of T-cell-mediated immunity in acute myeloid leukemia","volume":"39","author":"Li","year":"2020","journal-title":"Oncogene"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/11\/1226\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:21:09Z","timestamp":1760167269000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/11\/1226"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,22]]},"references-count":50,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["vaccines9111226"],"URL":"https:\/\/doi.org\/10.3390\/vaccines9111226","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.06.09.21258555","asserted-by":"object"}]},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,22]]}}}