Acquired Human Papilloma Virus Type 6-Associated Epidermodysplasia Verruciformis in a Patient With Systemic Lupus Erythematosus

Although historically known as a genetic disorder, epidermodysplasia verruciformis (EV) might be acquired in patients with a noninherited defective cell-mediated immunity. This article reports a case of EV in a patient with systemic lupus erythematosus and a history of 3 years immunosuppressive methylprednisolone treatment. The microscopic features of the skin biopsy showed morphologic changes of the keratinocytes characteristic of human papilloma virus (HPV) infections and immunoreactivity to p16. HPV genotyping demonstrated the presence of HPV 6 which belongs to a low-risk mucosal HPV group and has not been reported in EV previously. The clinical recognition of EV in immunocompromised patients and subsequent HPV typing is important because some patients will develop squamous cell carcinoma

Pathogenic mechanisms and clinical implications of congenital neutropenia syndromes

Purpose of reviewThe purpose of this review is to summarize pathogenic mechanisms and clinical implications of the most illustrative genetic entities of congenital neutropenia syndromes.Recent findingsCongenital neutropenia comprise monogenetic entities with or without additional immunologic and extrahaematopoietic syndromatic features. Continuous careful explorations of known entities such as ELANE, GFI1, HAX1, G6PC3 deficiency and XLN help to define principles controlling differentiation and function of neutrophil granulocytes. Furthermore, the identification of novel genetic defects associated with congenital neutropenia, such as VPS45 deficiency, broadens our understanding of neutrophil biology. Pathogenic mechanisms imply protein and vesicle mistrafficking, endoplasmic reticulum stress, the unfolded protein response, destabilization of the mitochondrial membrane potential, disturbed energy metabolism, dysglycosylation and deregulated actin polymerization.SummaryAdvanced genetic and biochemical techniques have helped to expand our knowledge of congenital neutropenia syndromes. Known and novel genetic entities shed light on fundamental biological processes important for the homeostatis and functioning not only of the neutrophil granulocyte but as well of the entire haematopoietic system. Furthermore, treatment decisions become more tailored and might pave the road towards personalized molecular medicine

Perceptions of sexual consent : the effects of eroticism and dominant gender in advertising.

This research investigates the impact that varying the levels of eroticism and gender of the dominant character in advertisements has on participants’ perceptions of sexual consent. Prior research has not examined these variables in conjunction; this study looks for both direct and interaction effects of eroticism and dominance on consent. Participants undertook an online questionnaire and were sorted into a control group which saw no image, or exposed to one of four images. These four conditions were manipulated by level of eroticism (non-erotic or eroticised), and by whether the male or female character was portrayed as more dominant. Participants then answered a series of questions relating to their attitudes about sexual consent. Image response data and demographic information was also collected. Results did not indicate any significant direct effects of eroticism or dominance on perceptions of sexual consent. However the interaction effect of these two variables did approach significance on two consent measures. Some of the image and consent measures were found to have small but significant correlations; significant covariate relationships were also identified. In particular, participants’ gender identity was found to impact the Positive Attitude Toward Establishing Consent and Verbal Consent Norms subscales; participants’ ethnicity had an effect on Positive Attitude Toward Establishing Consent, and their marital status had a significant effect on their Indirect Behavioural Approach To Consent. These relationships largely reinforce the work of previous scholars. These findings, as well as their implications, and suggestions for future research are discussed

Identification of novel genetic etiologies of susceptibility to EV-HPV infections

anti-CD3. Cependant, nous avons observé une augmentation significative des cellules T CD4+ mémoires et CD8+ effectrices mémoires et une augmentation de lymphocytes T CD4+ adressés à la peau. Ces anomalies résulteraient soit du défaut EVER, soit de l infection persistante par les EV-HPV, ou des deux. Nous avons ensuite identifié deux nouvelles étiologies génétiques de sensibilité aux infections par les EV-HPV. Les défauts en MST1 et RHOH sont tous les deux associés à une anomalie des lymphocytes T, caractérisée par une forte diminution des cellules T naïves, ont augmentation de cellules T mémoire et une altération de la prolifération des lymphocytes T en réponse à la stimulation à l anti-CD3. Contrairement aux patients déficients en EVER, ces patients présentent d'autres caractéristiques cliniques, en plus des infections persistantes symptomatiques par les EV-HPV. La découverte de ces deux nouveaux L épidermodysplasie verruciforme (EV) est une maladie génétique rare caractérisée par une sensibilité anormale à un groupe spécifique de betapapillomavirus (EV-HPV). Ces EV-HPV causent des lésions pityriasis versicolor-like et augmentent le risque de développer des cancers cutanés. Des mutations en épidermodysplasie verruciforme 1 (EVER1) ou EVER2 conduisant à la perte de fonction des protéines ont été identifiées dans la plupart des patients atteints d EV autosomique récessive. Il a été montré que les défauts de EVER1 et EVER2 altèrent l'homéostasie du zinc dans les kératinocytes. Nous avons étudié le phénotype des cellules T de patients présentant un défaut en EVER2 afin de tester l'hypothèse que ces patients souffrent également d'un défaut des lymphocytes T. Nous avons trouvé des comptes normaux de lymphocytes T CD4+ et CD8+ et une prolifération normale de ces cellules en réponse à une stimulation défauts suggère que les cellules T sont impliquées dans le contrôle de la sensibilité aux EV-HPV, au moins chez certains individusEpidermodysplasia verruciformis (EV) is a rare genetic disorder characterized by increased susceptibility to a specific group of related human betapapillomaviruses (EV-HPVs). These EV-HPVs cause pityriasis versicolor-like lesions and increase the risk of skin carcinomas in otherwise healthy individuals. Inactivating mutations in epidermodysplasia verruciformis 1 (EVER1) or EVER2 have been identified in most, but not all, patients with autosomal recessive EV. It was shown that EVER1 and EVER2 deficiencies alter zinc homeostasis in keratinocytes. We investigated the T-cell phenotype of EVER2-deficient patients in order to test the hypothesis that these patients also suffer from a T-cell deficiency. We found normal counts of CD4+ and CD8+ T cells and a normal proliferative capacity in response to anti-CD3 stimulation. However, we observed a significant increase of memory CD4+ and effector memory CD8+ T cells and an increase of skin-homing CD4+ T-cell subsets. It remains unclear whether these abnormalities result from EVER deficiency, or persistent EV-HPV infection, or both. We next identified two new genetic etiologies of susceptibility to EV-HPV infections. MST1 and RHOH deficiencies are both associated with an abnormal T-cell phenotype, characterized by strongly diminished naive T cells, increased memory T cells and impaired proliferative T-cell response to CD3 stimulation. In contrast to EVER-deficient patients, these patients have other clinical features in addition to persistent symptomatic EV-HPV infections. The discovery of these two new deficiencies suggests that T cells are involved in the control of EV-HPVs, at least in some individualsPARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF

Lipopolysaccharides from Commensal and Opportunistic Bacteria: Characterization and Response of the Immune System of the Host Sponge Suberites domuncula

Marine sponges harbor a rich bacterioflora with which they maintain close relationships. However, the way these animals make the distinction between bacteria which are consumed to meet their metabolic needs and opportunistic and commensal bacteria which are hosted is not elucidated. Among the elements participating in this discrimination, bacterial cell wall components such as lipopolysaccharides (LPS) could play a role. In the present study, we investigated the LPS chemical structure of two bacteria associated with the sponge Suberites domuncula: a commensal Endozoicomonas sp. and an opportunistic Pseudoalteromonas sp. Electrophoretic patterns indicated different LPS structures for these bacteria. The immunomodulatory lipid A was isolated after mild acetic acid hydrolysis. The electrospray ionization ion-trap mass spectra revealed monophosphorylated molecules corresponding to tetra- and pentaacylated structures with common structural features between the two strains. Despite peculiar structural characteristics, none of these two LPS influenced the expression of the macrophage-expressed gene S. domuncula unlike the Escherichia coli ones. Further research will have to include a larger number of genes to understand how this animal can distinguish between LPS with resembling structures and discriminate between bacteria associated with it

Neutrophils Oppose Uterine Epithelial Carcinogenesis via Debridement of Hypoxic Tumor Cells

Polymorphonuclear neutrophils (PMNs) are largely considered to foster cancer development despite wielding an arsenal of cytotoxic agents. Using a mouse model of PTEN-deficient uterine cancer, we describe a surprising inhibitory role for PMNs in epithelial carcinogenesis. By inducing tumor cell detachment from the basement membrane, PMNs impeded early-stage tumor growth and retarded malignant progression. Unexpectedly, PMN recruitment and tumor growth control occurred independently of lymphocytes and cellular senescence and instead ensued as part of the tumor's intrinsic inflammatory response to hypoxia. In humans, a PMN gene signature correlated with improved survival in several cancer subtypes, including PTEN-deficient uterine cancer. These findings provide insight into tumor-associated PMNs and reveal a context-specific capacity for PMNs to directly combat tumorigenesis