Human Polyomaviruses and Incidence of Cutaneous Squamous Cell Carcinoma in the New Hampshire Skin Cancer Study

Squamous cell carcinoma (SCC) of the skin is a malignancy arising from epi- thelial keratinocytes. Experimental and epidemiologic evidence raise the possibility that human polyomaviruses (PyV) may be associated with the occurrence of SCC. To investigate whether the risk for SCC was associated with PyV infection, seropositivity to 10 PyV types was assessed following diagnosis in a population- based case–control study conducted in the United States. A total of 253 SCC cases and 460 age group and gender-matched controls were included. Antibody response against each PyV was measured using a multiplex serology-based glu- tathione S-transferase capture assay of recombinantly expressed VP1 capsid proteins. Odds ratios (OR) for SCC associated with seropositivity to each PyV type were estimated using logistic regression, with adjustment for potentially confounding factors. SCC cases were seropositive for a greater number of PyVs than controls (P = 0.049). Those who were JC seropositive had increased odds of SCC when compared to those who were JC seronegative (OR = 1.37, 95% CI: 0.98–1.90), with an increasing trend in SCC risk with increasing quartiles of seroreactivity (P for trend = 0.04). There were no clear associations between SCC risk and serostatus for other PyV types. This study provides limited evi- dence that infection with certain PyVs may be related to the occurrence of SCC in the general population of the United States

Human Papillomavirus Antibodies And Future Risk Of Anogenital Cancer: A Nested Case-control Study In The European Prospective Investigation Into Cancer And Nutrition Study

Purpose: Human papillomavirus (HPV) type 16 (HPV16) causes cancer at several anatomic sites. In the European Prospective Investigation Into Cancer and Nutrition study, HPV16 E6 seropositivity was present more than 10 years before oropharyngeal cancer diagnosis and was nearly absent in controls. The current study sought to evaluate the extent to which HPV16 E6 antibodies are present before diagnosis of anogenital cancers within the same cohort. Methods: Four hundred incident anogenital cancers (273 cervical, 24 anal, 67 vulvar, 12 vaginal, and 24 penile cancers) with prediagnostic blood samples (collected on average 3 and 8 years before diagnosis for cervix and noncervix cancers, respectively) and 718 matched controls were included. Plasma was analyzed for antibodies against HPV16 E6 and multiple other HPV proteins and genotypes and evaluated in relation to risk using unconditional logistic regression. Results: HPV16 E6 seropositivity was present in 29.2% of individuals (seven of 24 individuals) who later developed anal cancer compared with 0.6% of controls (four of 718 controls) who remained cancer free (odds ratio [OR], 75.9; 95% CI, 17.9 to 321). HPV16 E6 seropositivity was less common for cancers of the cervix (3.3%), vagina (8.3%), vulva (1.5%), and penis (8.3%). No associations were seen for non-type 16 HPV E6 antibodies, apart from anti-HPV58 E6 and anal cancer (OR, 6.8; 95% CI, 1.4 to 33.1). HPV16 E6 seropositivity tended to increase in blood samples drawn closer in time to cancer diagnosis. Conclusion: HPV16 E6 seropositivity is relatively common before diagnosis of anal cancer but rare for other HPV-related anogenital cancers

Serological and hematological characteristics of Sjogren's syndrome and dry eye syndrome patients using a novel immune serology technique.

ObjectivesTo compare hematologic and serological parameters among patients with Sjogren's syndrome (SS), dry eye syndrome (DES) and controls, and validate a novel multiplex-serology method for identifying auto-antibodies in these populations.MethodsIn a clinic-based case-control study a total of 422 participants were recruited, including 91 with SS, 120 DES, and 211 controls (age and sex frequency-matched). We measured blood counts, anti-nuclear-antibodies (ANA), anti-SSA/SSB, anti-ribonucleoprotein (RNP), anti-double-stranded-DNA (DS-DNA), and rheumatoid factor (RF) using the "Immunodot" qualitative-ELISA assay. Immunoglobulins, C3 and C4 were measured by immune-fluorescence. Autoantibodies were also quantified with a newly-developed method using glutathione-S-transferase fusion proteins of SSA/Ro 52 and 60kD and SSB/La (multiplex-serology), measuring median fluorescence intensity (MFI).ResultsAmong DES patients, only 2% (95%CI: 0.36-6.3) had positive immune serology. SS patients had lower lymphocyte, hemoglobin and C3 levels but higher prevalence of RF, ANA, anti-SSA/B and higher IgG and MFI levels, compared to DES and controls (PConclusionsSerologic parameters distinguish SS from DES patients and controls. A newly-developed multiplex-serology technique may be useful to detect autoantibodies in large epidemiologic studies

Differences in Chlamydia trachomatis seroprevalence between ethnic groups cannot be fully explained by socioeconomic status, sexual healthcare seeking behavior or sexual risk behavior: a cross-sectional analysis in the HEalthy LIfe in an Urban Setting (HELIUS) study

Abstract Background In the Netherlands, there are strong disparities in Chlamydia trachomatis (CT) prevalence between ethnic groups. The current study aims to identify whether socioeconomic status, sexual risk behavior and sexual healthcare seeking behavior may explain differences in CT seroprevalence between ethnic groups. Methods We used 2011–2014 baseline data of the HELIUS (HEalthy LIfe in an Urban Setting) study, a multi-ethnic population-based cohort study in Amsterdam, the Netherlands, including participants from Dutch, African Surinamese, South-Asian Surinamese, Ghanaian, Moroccan and Turkish origin. For this analysis, we selected sexually active, heterosexual participants aged 18–34 years old. CT seroprevalence was determined using a multiplex serology assay. The CT seroprevalence ratios between different ethnicities are calculated and adjusted for potential indicators of socioeconomic status, sexual risk behavior and sexual healthcare seeking behavior. Results The study population consisted of 2001 individuals (52.8% female) with a median age of 28 years (IQR 24–31). CT seropositivity differed by ethnicities and ranged from 71.6% (African Surinamese), and 67.9% (Ghanaian) to 31.1% (Turkish). The CT seroprevalence ratio of African Surinamese was 1.72 (95% CI 1.43–2.06) and 1.52 (95% CI 1.16–1.99) of Ghanaian as compared to the Dutch reference group, after adjustment for socioeconomic status, sexual risk behavior and sexual healthcare seeking behavior. Conclusions Indicators of socioeconomic status, sexual risk behavior, and sexual health seeking behavior could not explain the higher CT seroprevalence among African Surinamese and Ghanaian residents of Amsterdam

The Glycome of Normal and Malignant Plasma Cells

<div><p>The glycome, i.e. the cellular repertoire of glycan structures, contributes to important functions such as adhesion and intercellular communication. Enzymes regulating cellular glycosylation processes are related to the pathogenesis of cancer including multiple myeloma. Here we analyze the transcriptional differences in the glycome of normal (n = 10) and two cohorts of 332 and 345 malignant plasma-cell samples, association with known multiple myeloma subentities as defined by presence of chromosomal aberrations, potential therapeutic targets, and its prognostic impact. We found i) malignant vs. normal plasma cells to show a characteristic glycome-signature. They can ii) be delineated by a lasso-based predictor from normal plasma cells based on this signature. iii) Cytogenetic aberrations lead to distinct glycan-gene expression patterns for t(11;14), t(4;14), hyperdiploidy, 1q21-gain and deletion of 13q14. iv) A 38-gene glycome-signature significantly delineates patients with adverse survival in two independent cohorts of 545 patients treated with high-dose melphalan and autologous stem cell transplantation. v) As single gene, expression of the phosphatidyl-inositol-glycan protein M as part of the targetable glycosyl-phosphatidyl-inositol-anchor-biosynthesis pathway is associated with adverse survival. The prognostically relevant glycome deviation in malignant cells invites novel strategies of therapy for multiple myeloma.</p></div

Upregulated genes and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways.

<p>Using the Goeman's global test method the degree of distinction between myeloma cell samples (MM) and normal bone marrow plasma cell (BMPC) samples was investigated. The significance of p-level indicates the degree of difference between then BMPC and the MM samples. Glycan pathways were ordered according to the general families of macromolecular glycan structures, i.e. GPI-anchored glycoproteins, N- and O-glycosylated glycoproteins, glycosphingolipids (GSL) and proteoglycans (heparan sulfate (GAG-HS) glycosaminoglycans (GAG); chondroitin sulfate (GAG-CS) and keratin sulfate (GAG-KS). Most significant changes in the MM glycome were found in the GPI- and in the HS synthesis and were highlighted.</p

Steps of heparan sulfate and GPI anchor biosynthesis.

<p><b>A</b>: Biosynthetical steps of the GAG-HS pathway and the functional role of the enzymes are shown. Green arrows indicate upregulated gene expression and red arrows downregulated gene expression. <b>B</b>: The steps of the GPI anchor biosynthesis are shown and the function of the proteins corresponding to the overexpressed <i>PIG</i>-genes M, C, B are shown.</p