495 research outputs found
Supplementary_TABLE_1_PALL_MED_PREDICTORS_OF_SURVIVAL_ADJUSTED_Files – Supplemental material for Disease trajectories, place and mode of death in people with head and neck cancer: Findings from the ‘Head and Neck 5000’ population-based prospective clinical cohort study
No full textSupplemental material, Supplementary_TABLE_1_PALL_MED_PREDICTORS_OF_SURVIVAL_ADJUSTED_Files for Disease trajectories, place and mode of death in people with head and neck cancer: Findings from the ‘Head and Neck 5000’ population-based prospective clinical cohort study by Catriona R Mayland, Kate Ingarfield, Simon N Rogers, Paola Dey, Steven Thomas, Andrea Waylen, Sam D Leary, Miranda Pring, Katrina Hurley, Tim Waterboer, Michael Pawlita and Andy R Ness in Palliative Medicine</p
Multiplex-Serologie - Simultane Analyse von Antikörper-Antworten gegen humane Papillomviren (HPV) mit Protein-Arrays
No full textMehr als 100 humane Papillomvirus (HPV)-Typen können den Menschen infizieren und teilweise maligne Erkrankungen auslösen. HPV-Seroepidemiologie erlaubt es, die Infektion und Krankheits-Assoziation von HPV zu untersuchen und Krebs-spezifische Antikörpermuster zu detektieren, wird jedoch durch die Vielfalt der Virustypen und -proteine und die Typspezifität der gegen sie gerichteten Antikörper erschwert. Der bisher zur Detektion von Antikörpern genutzte GST capture ELISA ist methodisch ausgereift und gut validiert, im Hinblick auf die Zahl parallel analysierbarer Antigene jedoch beschränkt. Ziel dieser Arbeit war daher die Entwicklung eines Antikörperscreeningsystems, das eine Hochdurchsatzanalyse von Seren auf Antikörper gegen viele in situ-affinitätsgereinigte Antigene in einem Reaktionsansatz erlaubt. Zwei solche Systeme wurden entwickelt: Ein auf Protein Microarray-Technologie basiertes System (Chip-ISA), für das sich die in situ-Affinitätsreinigung der Antigene nicht realisieren ließ, und ein System namens Multiplex-Serologie, das auf einem Suspensions-Array von farbkodierten Polystyrolbeads beruht, die sich in einem Duchflusszytometer unterscheiden lassen. Nach Etablierung einer Methodik zur Derivatisierung dieser Beads mit Glutathion konnten die als GST-Fusionsproteine exprimierten Antigene direkt aus Bakterienlysat aufgereinigt werden. Multiplex-Serologie wurde vollständig validiert und ist gut reproduzierbar, sehr sensitiv und spezifisch. Die Methode wurde zur Analyse großer Serumzahlen adaptiert und erlaubt jetzt die Untersuchung von bis zu 1000 Seren auf Antikörper gegen bis zu 100 simultan getestete Antigene pro Tag. Über die technische Entwicklung hinaus wurden mit Multiplex-Serologie verschiedene seroepidemiologische Studien analysiert und die Ergebnisse von dreien im Detail vorgestellt. Erstmals wurde die Seroprävalenz gegen die L1-Proteine von 13 HPV-Typen in der deutschen Normalbevölkerung untersucht und auf Alters- und geschlechtsabhängige Dynamik analysiert. In einer zweiten Studie wurde die Assoziation von Antikörpern gegen die L1-Proteine einiger sogenannter EV-HPV-Typen mit nicht melanotischem Hautkrebs untermauert. Ebenfalls zum ersten mal wurde gezeigt, dass typspezifische Antikörper gegen die E6- und E7-Proteine seltener sogenannter Hoch-Risiko-HPV-Typen existieren und mit Zervix-Karzinomen assoziiert sind. Die Entwicklung von Multiplex-Serologie erlaubt erstmals die simultane Analyse von komplexen Antikörperantworten gegen bis zu 100 Proteine und stellt möglicherweise einen Quantensprung für (HPV-)Seroepidemiologie dar
Comparison of a VLP‐based and GST‐L1‐based multiplex immunoassay to detect vaccine‐induced HPV‐specific antibodies in first‐void urine
No full textVaccine-induced human papillomavirus (HPV) antibodies originating from cervicovaginal secretions were recently shown to be detectable in first-void (FV) urine. This presents a novel opportunity for noninvasive sampling to monitor HPV antibody status in women participating in large epidemiological studies and HPV vaccine trials. With a view towards method optimization, this study compared the measurement of HPV antibodies in FV urine using a multiplex L1/L2 virus-like particles (VLP)-based ELISA (M4ELISA) with previously reported results using a glutathione S-transferase (GST)-L1-based immunoassay (GST-L1-MIA). We tested 53 paired FV urine and serum samples from 19- to 26-year-old healthy women, unvaccinated (n = 17) or vaccinated with either the bivalent or quadrivalent HPV-vaccine during adolescence (n = 36). HPV6/11/16/18 antibodies were measured using M4ELISA and compared with GST-L1-MIA results. Inter-assay and inter-specimen correlations were examined using the Spearman's rank test (rs). As expected, lower HPV antibody concentrations were found in FV urine than in serum. Vaccinated women had significantly higher HPV6/11/16/18 antibody levels in both FV urine and serum compared with those unvaccinated (M4ELISA; FV urine P = .0003; serum P <= .0001). HPV antibody levels in FV urine and serum showed a significant positive correlation (M4ELISA anti-HPV6/11/16/18, r(s) = 0.85/0.86/0.91/0.79, P <= .001). Despite assay differences, there was moderate to good correlation between M4ELISA and GST-L1-MIA (FV urine anti-HPV6/11/16/18, r(s) = 0.86/0.83/0.89/0.53, P <= .0001; serum anti-HPV6/11/16/18, r(s) = 0.93/0.89/0.94/0.75, P <= .0001). FV urine HPV antibody detection is comparable with both assays, further supporting this noninvasive sampling method as a possible option for HPV vaccine assessment. Approaches to improve the sensitivity and larger studies are warranted to determine the feasibility of FV urine for vaccine-induced HPV antibody detection.Industrial Research Fund of the University of Antwerp, Belgium, Grant/Award Number: PS ID 32387Pattyn, J (reprint author), Campus Drie Eiken,Bldg R2,Univ Pl 1, B-12610 Antwerp, Belgium.
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Amino Acid Variation in HLA Class II Proteins Is a Major Determinant of Humoral Response to Common Viruses
No full textThe magnitude of the human antibody response to viral antigens is highly variable. To explore the human genetic contribution to this variability, we performed genome-wide association studies of the immunoglobulin G response to 14 pathogenic viruses in 2,363 immunocompetent adults. Significant associations were observed in the major histocompatibility complex region on chromosome 6 for influenza A virus, Epstein-Barr virus, JC polyomavirus, and Merkel cell polyomavirus. Using local imputation and fine mapping, we identified specific amino acid residues in human leucocyte antigen (HLA) class II proteins as the most probable causal variants underlying these association signals. Common HLA-DRβ1 haplotypes showed virus-specific patterns of humoral-response regulation. We observed an overlap between variants affecting the humoral response to influenza A and EBV and variants previously associated with autoimmune diseases related to these viruses. The results of this study emphasize the central and pathogen-specific role of HLA class II variation in the modulation of humoral immune response to viral antigens in humans
Human papillomavirus in benign prostatic hyperplasia and prostatic adenocarcinoma patients
No full textThe aim of this study was to determine the prevalence of human papillomavirus (HPV) types in tissue and HPV antibodies in prostatic disease. Prostate tissue samples were collected from 51 patients diagnosed with adenocarcinoma and 11 with benign prostatic hyperplasia (BPH). All tissue samples were confirmed by histology. Plasma samples were available for 52 prostate patients. We investigated HPV DNA prevalence by PCR, and PCR positive samples were HPV type determined by sequencing. Prevalence of antibodies against twenty-seven HPV proteins from fourteen different HPV types was assessed in the plasma samples. The HPV DNA prevalence in the tissue samples was 14% (7/51) for prostate cancer samples and 27% (3/11) for BPHs. HPV-18 was the only type detected in tissue samples (10/62). No significant difference in HPV prevalence between the prostate cancer and BPH samples was found. HPV-positive cells were identified in eight of our thirteen prostate tissue slides (3/3 BPH and 5/10 adenocarcinoma) by in situ hybridisation, and the positive cells were found in epithelial cells and peripheral blood cells. Serology data showed no significant increase in levels of antibodies against any of the HPV-18 proteins tested for in prostatic disease patients. Antibodies against HPV-1, HPV-4, HPV-6 and HPV-11 were significantly higher in the group of males with prostatic disease. Our study did not show an association between prostatic disease and either presence of HPV DNA in samples or previous exposure of high-risk HPV.Alice C.-H. Chen, Tim Waterboer, Annie Keleher, Beth Morrison, Shalini Jindal, Denise McMillan, David Nicol, Robert A. Gardiner, Nigel A.J. McMillan and Annika Antonsso
Prognostic significance of spontaneous antibody responses against tumor-associated antigens in malignant melanoma patients
No full textDistribution, patterns and prognostic impact of spontaneous antibody responses against different tumor-associated antigens (TAAs) in malignant melanoma patients are unknown so far and were investigated in this study for the first time in a large cohort at different stages of the disease, identifying new prognostic biomarkers for malignant melanoma. Serum samples from 365 melanoma patients (97 Stage I melanoma patients, 87 Stage II, 92 Stage III and 89 Stage IV) and 100 age and gender matched healthy control donors were analyzed. Samples were drawn at the time of diagnosis (Stages I-III) or at time of diagnosis of distant metastasis (Stage IV). Applying a novel multiplex assay, humoral immune responses against 29 TAAs were determined and the association between response and patient survival was investigated. Antibody responses were mainly found in melanoma patients and all tested antigens elicited immune responses in all disease stages. Antibody responses against single antigens were either associated with poor prognosis and/or shorter progression-free survival (PFS) or had no influence. While in Stages I-III significant associations were observed between an antibody response and overall survival or PFS, among Stage IV patients, no significant association was found. Multivariate analyses identified specific humoral immune responses as prognostic factors independently of age, chemotherapy and immunotherapy. Antibody responses against specific TAA in Stage I-III melanoma patients correlate with poor prognosis and/or shorter PFS. These results may help to design clinical studies in order to evaluate the potential of these responses as prognostic serological biomarkers
Seroprevalence of sexually transmitted infections over 44 years : a cross-sectional study in Sweden
No full textBackground: Sexually transmitted infections (STIs) may cause substantial individual suffering and a large economic burden for society. This study examined the seroprevalence of Chlamydia trachomatis, Mycoplasma genitalium, herpes simplex virus (HSV) types 1 and 2, and several human papillomaviruses (HPV) in the Swedish population over time. Methods: The study population consisted of 30-year-old women attending maternity care, and 50 year-old men and women attending health check-ups, from 1975 to 2018. Antibody status was determined by multiplex serology and quantified using median reporter fluorescence intensity (MFI). Results: A total of 891 samples were analysed (519 from 30-year-old women, 186 from 50 year-old women and 186 from 50 year-old men). Of these, 41.5% showed seropositivity for Chlamydia trachomatis, 16.7% for Mycoplasma genitalium, 70.5% for HSV-1, 14.9% for HSV-2, 13.2% for high-risk HPV, and 8.3% for low-risk HPV. Seropositivity for Mycoplasma genitalium, HSV-1 and especially Chlamydia trachomatis decreased over time. Conclusions: There was a decrease over time in Chlamydia trachomatis seroprevalence, probably due to contact tracing, testing and early treatment; this might also have affected Mycoplasma genitalium seroprevalence. Despite the reduction, seroprevalences are still high, so continued and new efforts to reduce STI incidence are essential
Regression of Cutaneous Warts in a Patient With WILD Syndrome Following Recombinant Quadrivalent Human Papillomavirus Vaccination
No full textSensitivity and specificity of antibodies against HPV16 E6 and other early proteins for the detection of HPV16-driven oropharyngeal squamous cell carcinoma
No full textTo determine the sensitivity and specificity of HPV16 serology as diagnostic marker for HPV16-driven oropharyngeal squamous cell carcinoma (OPSCC), 214 HNSCC patients from Germany and Italy with fresh-frozen tumor tissues and sera collected before treatment were included in this study. 120 cancer cases were from the oropharynx and 94 were from head and neck cancer regions outside the oropharynx (45 oral cavity, 12 hypopharynx and 35 larynx). Serum antibodies to early (E1, E2, E6 and E7) and late (L1) HPV16 proteins were analyzed by multiplex serology and were compared to tumor HPV RNA status as the gold standard. A tumor was defined as HPV-driven in the presence of HPV16 DNA and HPV16 transformation-specific RNA transcript patterns (E6*I, E1^E4 and E1C). Of 120 OPSCC, 66 (55%) were HPV16-driven. HPV16 E6 seropositivity was the best predictor of HPV16-driven OPSCC (diagnostic accuracy 97% [95%CI 92-99%], Cohen's kappa 0.93 [95%CI 0.8-1.0]). Of the 66 HPV-driven OPSCC, 63 were HPV16 E6 seropositive, compared to only one (1.8%) among the 54 non-HPV-driven OPSCC, resulting in a sensitivity of 96% (95%CI 88-98) and a specificity of 98% (95%CI 90-100). Of 94 HNSCC outside the oropharynx, 6 (6%) were HPV16-driven. In these patients, HPV16 E6 seropositivity had lower sensitivity (50%, 95%CI 19-81), but was highly specific (100%, 95%CI 96-100). In conclusion, HPV16 E6 seropositivity appears to be a highly reliable diagnostic marker for HPV16-driven OPSCC with very high sensitivity and specificity, but might be less sensitive for HPV16-driven HNSCC outside the oropharynx
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