Expanding phenotype of hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis caused by FAM111B mutations: Report of an additional family raising the question of cancer predisposition and a short review of early-onset poikiloderma.

journal article2017 Mar2017 03 19importedHereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP [MIM#615704]) is an extremely rare syndromic form of autosomal dominant poikiloderma. This genetic disorder was first identified in a South African family in 2006.1 To date, 3 families and 9 independent sporadic cases have been reported.2-4 Here we report an additional family of POIKTMP and expand the clinical spectrum. We describe, for the first time to our knowledge, a pancreatic cancer in the clinical course in 1 patient

Characterization of HLA-DQalpha2/beta2, a new HLA class II molecule specifically expressed in human Langerhans cells

Les cellules de Langerhans sont les cellules dendritiques résidentes de l'épiderme humain, occupant ainsi une position privilégiée à l'interface du corps et de l'environnement extérieur. Afin de mieux appréhender leur spécificité parmi les différentes celLangerhans cells are the resident dendritic cells of the human epidermis, wherein they occupy a privileged position at the interface between the body and the external environment. To refine our knowledge on their specificities among the dendritic cells,

Dermatoses inflammatoires blaschkolinéaires de l'adulte

STRASBOURG-Medecine (674822101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Caractérisation des molécules HLA-DQa2/b2, un nouveau type de molécules HLA de classe II exprimées par les cellules de Langerhans de l épiderme

Les cellules de Langerhans sont les cellules dendritiques résidentes de l épiderme humain, occupant ainsi une position privilégiée à l interface du corps et de l environnement extérieur. Afin de mieux appréhender leur spécificité parmi les différentes cellules dendritiques, le laboratoire a entrepris un projet d analyse comparative de leur transcriptome, qui a permis d identifier l expression préférentielle du gène HLA-DQB2 par les cellules de Langerhans. Les gènes HLA-DQA2/DQB2 sont les paralogues des gènes HLA-DQA1/DQB1 encodant les molécules présentatrices d antigène HLA-DQ, mais sont remarquablement peu polymorphes comparés à ces derniers, et fortement conservés au cours de l évolution. De manière remarquable, leur expression coordonnée n avait jamais été détectée jusqu ici. Au cours de ces travaux, nous confirmons que les gènes HLA-DQA2 et HLA-DQB2 sont exprimés spécifiquement par les cellules de Langerhans. Grâce à l utilisation de différents modèles de cellules transfectées, nous montrons que les chaines HLA-DQa2 et HLA-DQb2 s assemblent dans le réticulum endoplasmique pour être exportées à destination des compartiments endosomaux grâce à la chaîne invariante Ii, chaperon des molécules HLA de classe II. Les molécules HLA-DQa2/b2 interagissent avec le chaperon endosomal HLA-DM et sont exprimées à la surface des cellules, où elles peuvent relayer la stimulation de lymphocytes T par un superantigène staphylococcique. Ces résultats suggèrent que les molécules HLA-DQa2/b2 constituent un nouveau type de molécules HLA de classe II très peu polymorphes, exprimées spécifiquement par les cellules de Langerhans de l épiderme.Langerhans cells are the resident dendritic cells of the human epidermis, wherein they occupy a privileged position at the interface between the body and the external environment. To refine our knowledge on their specificities among the dendritic cells, a comparative analysis of their transcriptome was undertaken in the laboratory. In this way, the specific expression of the HLA-DQB2 gene by Langerhans cells was identified. HLA-DQA2/DQB2 genes are paralogous to the HLA-DQ-encoding HLA-DQA1/DQB1 genes, but have been described as remarkably lowly polymorphic for HLA class II genes and are strongly evolutionarily conserved. Up to date, their coordinated expression has never been reported. In this work, we confirm that HLA-DQA2 and HLA-DQB2 genes are specifically expressed in Langerhans cells. With the help of different transfected cell line models, we show that the HLA-DQa2 and HLA-DQb2 chains associate together in the endoplasmic reticulum and, under the control of the chaperone invariant chain Ii, reach endosomal compartments. HLA-DQa2/b2 molecules interact with the endosomal chaperone HLA-DM and are expressed at the plasma membrane, where they mediate staphylococcal superantigen presentation to T cells. Taken together, those results suggest that HLA-DQa2/b2 molecules could represent a new type of lowly polymorphic HLA class II molecules specifically expressed in epidermal Langerhans cells.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Human Co-Infections between <i>Borrelia burgdorferi</i> s.l. and Other <i>Ixodes</i>-Borne Microorganisms: A Systematic Review

When it comes to tick-borne diseases, co-infections are often mentioned. This concept includes several entities. On the one hand, tick vectors or vertebrate reservoir host can harbor several microorganisms that can be pathogenic for humans. On the other hand, human co-infections can also be understood in different ways, ranging from seropositivity without clinical symptoms to co-disease, i.e., the simultaneous clinical expression of infections by two tick-borne microorganisms. The latter, although regularly speculated, is not often reported. Hence, we conducted a systematic review on co-infections between B. burgdorferi s.l., the etiological agent of Lyme borreliosis, and other microorganisms potentially transmitted to humans by Ixodes spp. ticks. A total of 68 relevant articles were included, presenting 655 cases of possible co-infections. Most cases of co-infections corresponded to patients with one tick-borne disease and presenting antibody against another tick-borne microorganism. Co-disease was particularly frequent in two situations: patients with clinical symptoms of high fever and erythema migrans (EM), and patients with neurological symptoms linked to the TBEv or a neuroborreliosis. No impact on severity was evidenced. Further studies are needed to better appreciate the frequency and the impact of co-infections between several tick-borne microorganisms

Skin Interface, a Key Player for Borrelia Multiplication and Persistence in Lyme Borreliosis

International audienceThe skin plays a key role in vector-borne diseases because it is the site where the arthropod coinoculates pathogens and its saliva. Lyme borreliosis, particularly well investigated in this context, is a multisystemic infectious disease caused by Borrelia burgdorferi sensu lato and transmitted by the hard tick Ixodes. Numerous in vitro studies were conducted to better understand the role of specific skin cells and tick saliva in host defense, vector feeding, and pathogen transmission. The skin was also evidenced in various animal models as the site of bacterial multiplication and persistence. We present the achievements in this field as well as the gaps that impede comprehensive knowledge of the disease pathophysiology and the development of efficient diagnostic tools and vaccines in humans. Copyright © 2020 Elsevier Ltd. All rights reserved

Multiple erythema migrans and carditis-related atrial fibrillation: exceptional manifestations of early disseminated Lyme disease

International audienc

TRB3 inhibits the transcriptional activation of stress-regulated genes by a negative feedback on the ATF4 pathway

International audienceThe integrated stress response (ISR) is defined as a highly conserved response to several stresses that converge to the induction of the activating transcription factor 4 (ATF4). Because an uncontrolled response may have deleterious effects, cells have elaborated several negative feedback loops that attenuate the ISR. In the present study, we describe how induction of the human homolog of Drosophila tribbles (TRB3) attenuates the ISR by a negative feedback mechanism. To investigate the role of TRB3 in the control of the ISR, we used the regulation of gene expression by amino acid limitation as a model. The enhanced production of ATF4 upon amino acid starvation results in the induction of a large number of target genes like CHOP (CAAT/enhancer-binding protein-homologous protein), asparagine synthetase (ASNS), or TRB3. We demonstrate that TRB3 overexpression inhibits the transcriptional induction of CHOP and ASNS whereas TRB3 silencing induces the expression of these genes both under normal and stressed conditions. In addition, transcriptional profiling experiments show that TRB3 affects the expression of many ISR-regulated genes. Our results also suggest that TRB3 and ATF4 belong to the same protein complex bound to the sequence involved in the ATF4-dependent regulation of gene expression by amino acid limitation. Collectively, our data identify TRB3 as a negative feedback regulator of the ATF4-dependent transcription and participates to the fine regulation of the ISR

The ABC of Hidradenitis Suppurativa:A Validated Glossary on how to Name Lesions

Background: The precise clinical description of skin lesions observed in some patients with hidradenitis suppurativa (HS) can be extremely difficult. Objective: Establishing a validated glossary of terms allowing the best possible description of lesions observed in HS patients. Material and Methods: Five international experts of HS were to assess a series of 25 photos representing typical lesions of this disorder. For each photo, the experts were asked whether naming of the lesions was possible or not and, if yes, by using which noun. Agreement of their responses was calculated using Fleiss's kappa index. Using a Delphi strategy, photos with disagreement were discussed, and photos were reevaluated on the next day. In case of agreement on the impossibility of naming some clinical situations, new terms, to be included into the glossary, were agreed upon. Results: After the first round of photos, agreement between the experts was poor with a kappa index of only 0.33 (95% CI 0.22-0.46). After extensive discussion of cases with disagreement, the kappa index increased on day 2 to 0.75 (95% CI 0.60-0.87), allowing to conclude on good interobserver agreement on terminology. Furthermore, a few clinical situations were identified in which naming with established semantics is so far not possible. For these situations, the terms ‘multicord', ‘multipore', ‘multitunnel' and ‘retraction' were defined. Discussion: This is the first validation of clinical terms used to describe lesions in patients with HS. This should be helpful in better defining the clinical phenotypes observed in this disorder