BK polyomavirus (BKPyV) often reactivates after kidney transplantation, causing BKPyV-associated nephropathy (BKPyVAN) in 1%-10% of cases with a potential detrimental effect on allograft survival. Kidney transplant recipients are regularly screened for BKPyV DNA in plasma. As this strategy may not always reduce the risk of BKPyVAN, other predictive markers are needed. To evaluate the role of pretransplant BKPyV-specific antibody, 210 kidney transplant recipients and 130 donors were screened for BKPyV DNA and BKPyV-specific antibodies. We found that the donor BKPyV immunoglobulin G (IgG) seroprevalence and antibody level were strongly associated with BKPyV-DNAemia and BKPyVAN, although multivariant analysis found the presence of anti-BKPyV-specific antibodies as a predictive factor only for BKPyV-DNAemia. The pretransplant recipient status had no effect on posttransplant BKPyV-DNAemia and BKVAN. BKPyV IgG levels remained stable in BKPyV-negative recipients during 1-year follow-up, while a considerable increase was observed in BKPyV-positive patients. The presence of anti-BKPyV-specific antibodies in kidney allograft donors is a good and reliable predictive marker for posttransplant BKPyV replication with relevance to risk stratification in transplant recipients.
Importance: Recurrent respiratory papillomatosis (RRP) is a rare benign chronic disease of the larynx etiologically linked with the infection of low-risk human papillomavirus (HPV). Combination of surgical and immunomodulatory therapy has limited success. Possible use of prophylactic HPV vaccine that includes HPV-6 and HPV-11 antigens has been studied. Objective: To evaluate if the HPV vaccination is associated with a lower number of recurrences requiring surgical intervention in patients with new and recurrent RRP. Design, Setting, and Participants: This was a non-placebo-controlled intervention study. Enrollment data were collected from October 2011 to August 2013. The patients were followed up at 1 month, 12 months, and 5 years after the third dose of the vaccine and clinically monitored until December 31, 2018. Data were analyzed from 2019 to 2021. Altogether, 50 adults with active RRP were enrolled and followed up in referral centers. For the final outcome, follow-up data for 42 patients were available. Eight patients who did not fulfill the protocol were excluded. Interventions: All patients received HPV vaccine as an adjuvant treatment and were clinically followed up. When RRP progression or a significant recurrent lesion was detected, surgical removal via direct laryngoscopy was indicated. No adjuvant therapy with antiviral or biological agents was used. Main Outcomes and Measures: This study compared the prevaccination and postvaccination positivity for HPV-specific antibodies. The main outcome was the difference in the frequency of RRP recurrences in the prevaccination and postvaccination period. Results: A total of 50 patients with RRP were enrolled (median [SD] age, 41.5 [12.3] years [range, 21-73 years]; 39 [78%] men and 11 [22%] women). After HPV vaccination, patients with previously no HPV-specific antibodies showed seroconversion, and all patients developed 100-fold higher levels of HPV vaccine type-specific antibodies compared with the prevaccination period. In patients with recurrent RRP, decreased frequency of recurrences requiring surgical treatment was present after vaccination (from 0.85 to 0.36 recurrences/y). No difference in postvaccination recurrences was found between patients with newly diagnosed and recurrent RRP. Conclusions and Relevance: In this nonrandomized clinical trial, the frequency of RRP recurrences was significantly lower after HPV vaccination, and patients with RRP thus had a reduced burden of disease. Because no difference was detected in the frequency of recurrent postvaccination lesions in patients with new and recurrent disease, it appears that both groups showed equal benefit following HPV vaccination. These findings suggest that the earlier that patients with RRP receive HPV vaccine, the sooner they may show reduced burden of disease. Trial Registration: EudraCT Identifier: 2011-002667-14; ClinicalTrials.gov Identifier: NCT01375868.
- MeSH
- Alphapapillomavirus * MeSH
- dospělí MeSH
- infekce dýchací soustavy * prevence a kontrola MeSH
- infekce papilomavirem * prevence a kontrola MeSH
- lidé MeSH
- vakcinace MeSH
- vakcíny proti papilomavirům * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
- MeSH
- DNA testy na papilomavirus metody MeSH
- klinické laboratorní techniky MeSH
- lidé MeSH
- lidské papilomaviry * izolace a purifikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
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-2nd 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 "non-reactive" 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-γ 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.
- Publikační typ
- časopisecké články MeSH
Background/Aim: The incidence of oropharyngeal tumours induced by human papillomaviruses (HPV) is ever increasing. Information about oral HPV prevalence and its risk factors are very important for future screening and early diagnosis of the disease. The present study aimed to assess oral HPV prevalence in healthy population and risk factors for HPV infection, since this data is scarce or even missing in Central Europe. Patients and Methods: HPV prevalence in oral rinse and HPV-specific antibodies in peripheral blood were investigated in two groups of healthy participants. Group I consisted of 294 students who reached sexual maturity after the HPV vaccine had been licensed with mean age 23.2 years, and Group II of 215 unvaccinated participants with the mean age 55.7 years. Additionally, the risk factors were evaluated. Results: In Group I, 2% of participants were positive for oral HPV DNA. A statistically significantly higher rate (8.8%) was found in Group II. The seropositivity rates for anamnestic HPV antibodies were comparable in both groups. None of the analysed risk factors was significantly associated with oral HPV positivity. Conclusion: The lower prevalence of oral HPV DNA in younger participants suggests the positive influence of vaccination against oral HPV.
- MeSH
- dospělí MeSH
- infekce papilomavirem epidemiologie virologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- patologie ústní dutiny MeSH
- prevalence MeSH
- rizikové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
- Publikační typ
- abstrakt z konference MeSH
Adoptive transfer of multivirus-specific T cell lines (MVST) is an advanced tool for immunotherapy of virus infections after hematopoietic stem cell transplantation (HSCT). Their preparation includes activation of donor virus-specific T cells by the mixture of oligopeptides derived from immunodominant antigens of several most harmful viruses, i.e. human cytomegalovirus (HCMV), polyomavirus BK (BKV), Epstein-Barr virus (EBV) and adenovirus (ADV). The aim of our study was to find out whether antigenic competition may have an impact on the expansion of virus-specific T cells. MVST from several heathy blood donors were generated using a pulse of overlapping oligopeptides (PepMixes™, derived from the IE1 and pp65 CMV antigens, VP1 and LTAG BKV antigens, BZLF1 and EBNA1 proteins of EBV and hexon protein from ADV) and short time culture in the presence of IL-7 and IL-4. The amount of virus-specific T cells in MVST was measured by ELISPOT and flow cytometry after re-stimulation with individual antigens. To evaluate antigenic competition, MVST were expanded either with a complete set of antigens or with the mixture lacking some of them. MVST expanded with the antigen mixture including CMV antigens contained a lower proportion of the T cells of other antigen specificities. A similar inhibitory effect was not apparent for EBV-derived peptides. The competitive effect of CMV antigens was most pronounced in MVST from CMV-seropositive donors and was mediated by both IE1 and pp65-derived peptides. Antigenic competition did not influence the phenotype of either CMV- or BKV-specific T cells. Both T cell populations had an effector memory phenotype (CD45RO+, CD27-, CCR7-). However, CMV-specific T cells preferentially consist of CD8+ while in BKV-specific T cells, the CD4+ phenotype predominated. Modification of the MVST manufacture protocol to prevent antigenic competition may increase the efficacy of MVST in therapy of BKV infections in HSCT recipients.
- MeSH
- Adenoviridae imunologie patogenita MeSH
- adenovirové infekce lidí imunologie terapie virologie MeSH
- aktivace lymfocytů MeSH
- antigeny virové imunologie MeSH
- cytomegalovirové infekce imunologie terapie virologie MeSH
- Cytomegalovirus imunologie patogenita MeSH
- fenotyp MeSH
- imunodominantní epitopy MeSH
- imunoterapie adoptivní * MeSH
- infekce onkogenními viry imunologie terapie virologie MeSH
- infekce virem Epsteina-Barrové imunologie terapie virologie MeSH
- interakce hostitele a patogenu MeSH
- kultivované buňky MeSH
- lidé MeSH
- polyomavirové infekce imunologie terapie virologie MeSH
- T-lymfocyty imunologie transplantace virologie MeSH
- transplantace hematopoetických kmenových buněk škodlivé účinky MeSH
- virové nemoci imunologie terapie virologie MeSH
- virus BK imunologie patogenita MeSH
- virus Epsteinův-Barrové imunologie patogenita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The presence of human papillomavirus (HPV)-specific antibodies in patients with head and neck cancer at enrollment has prognostic significance. In cervical carcinoma patients, the decrease of HPV E6/E7-specific antibodies appears to be associated with a better prognosis. METHODS: This prospective study with follow-up focused on the persistence and prognostic value of antibodies specific for HR HPV-derived VLPs and HPV16 E6/E7 oncoproteins in patients with oropharyngeal cancers. In this study, we analyzed sera of 93 patients taken a year after the end of treatment and sera from 58 of these patients taken up to 14 years after treatment. RESULTS: The level of HPV-specific antibodies decreased on the 1-year follow-up and the decrease during the long follow-up was statistically significant. For HPV16 E7 antibodies the decrease was steeper in nonrecurrent patients. While the level of antibodies at enrollment was not predictive of recurrences, the decrease of HPV16 E6 antibodies at 1-year follow up was associated with better overall as well as disease-specific survival of patients. CONCLUSIONS: The data suggest that the pretreatment level of HPV-specific antibodies is not predictive of the occurrence of recurrences but the decrease HPV16 E6 antibodies on the 1-year follow-up is predictive of better survival of HN patients.
- MeSH
- časové faktory MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidský papilomavirus 16 imunologie MeSH
- míra přežití MeSH
- nádory orofaryngu krev mortalita terapie MeSH
- následné studie MeSH
- onkogenní proteiny virové imunologie MeSH
- Papillomavirus E7 - proteiny imunologie MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- prospektivní studie MeSH
- protilátky virové krev MeSH
- represorové proteiny imunologie MeSH
- skvamocelulární nádory krev mortalita terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Úvod: Lidské papilomaviry (HPV), patřící do skupiny malých nádorových DNA virů, jsou kauzálně spojeny s karcinomem děložního hrdla a částí dalších anogenitálních, orálních a orofaryngeálních karcinomů mužů i žen. Cílem tohoto systematického přehledu je přinést souhrnné aktuální informace o výskytu orálních HPV u zdravé populace v Evropě. Metodika: Systematický přehled evropských studií o prevalenci orálních HPV infekcí publikovaných od ledna 2011 do září 2017. Výsledky: Celková prevalence orálních HPV infekcí u zdravé populace se pohybuje v rozmezí 1,2-11,6 %, vysoce rizikové typy HPV (HR HPV) byly nalezeny u 2,2-7,2 % a typ HPV16 u 0,2-2,9 % jedinců. Celková prevalence orálních HPV infekcí byla výrazně vyšší u mužů, kteří měli sex s muži, ve srovnání s heterosexuálními muži a ženami. Závěr: Prevalence orální HPV infekce v evropských populacích je srovnatelná s výsledky studií z USA a Asie. Na rizikové faktory orální HPV infekce u zdravé populace se však evropské studie příliš nezaměřovaly. Statisticky významný vztah mezi orálním sexem, kouřením a orální HPV infekcí, pozorovaný v rozsáhlých studiích z USA, potvrdila jen jedna evropská studie.
Background: Human papillomaviruses (HPV), a group of small, tumorigenic DNA viruses, are causally linked to cervical cancer and various other anogenital, oral, and oropharyngeal malignancies in both males and females. The purpose of this systematic review is to summarize the most recent data on the prevalence of oral HPV in healthy populations in Europe. Methods: A systematic review of the European studies on the prevalence of oral HPV infections published from January 2011 to September 2017. Results: The overall prevalence rates of oral HPV in healthy populations vary between 1.2% and 11.6%, with high-risk types of HPV (HR HPV) detected in 2.2% to 7.2% of individuals and HPV16 in 0.2% to 2.9% of individuals. The overall prevalence rate of oral HPV infections was considerably higher in men having sex with men as compared to heterosexual men and women. Conclusion: The prevalence rates of oral HPV infection in European populations are comparable to the results of the studies conducted in the USA and Asia. However, the European studies did not focus on the risk factors for oral HPV infection in healthy populations. A statistically significant relationship between oral sex, smoking, and HPV infection as observed in extensive studies from the USA was confirmed by a single European study.
- MeSH
- infekce papilomavirem * patologie přenos MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- polymerázová řetězová reakce MeSH
- prevalence MeSH
- rizikové faktory MeSH
- ústa * patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
- Geografické názvy
- Evropa MeSH
As the extent of centrosome abnormalities in chronic myeloid leukemia (CML) correlates with disease stage and karyotype alterations, abnormal expression of genes encoding centrosomal proteins may be an early prognostic marker of disease progression. In the present study, we showed that in comparison with healthy controls, the expression of four centrosomal genes (AURKA, HMMR, PLK1 and ESPL1) in the peripheral blood of CML patients was significantly enhanced at diagnosis and decreased to the basal level in most patients treated with imatinib mesylate for three months. In the remaining patients (17%), this decrease was delayed and was associated with worse overall survival. The detection of antibodies in sera showed that patients with higher overall antibody production had superior outcomes in terms of achieving major molecular response and failure-free survival. These data suggest that the dynamics of the response of centrosomal genes should be considered as a risk factor and immunity against centrosomal proteins may contribute to treatment response.
- MeSH
- centrozom imunologie metabolismus MeSH
- chronická myeloidní leukemie genetika imunologie MeSH
- dospělí MeSH
- humorální imunita * genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nádorové proteiny genetika imunologie MeSH
- proteiny buněčného cyklu genetika imunologie MeSH
- regulace genové exprese u leukemie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
