Involvement of membrane CD83 / soluble CD83 in autoimmune pemphigus

Le pemphigus est un groupe hétérogène de maladies bulleuses auto-immunes intra-épithéliales où les lymphocytes B produisent des auto-anticorps pathogènes directement responsables des lésions bulleuses et érosives, cutanées et muqueuses. Les thérapeutiques ciblées déplétant les lymphocytes B (LB) telles que les anticorps monoclonaux anti-CD20 (RTX) ont permis d’améliorer grandement le pronostic des patients. Cependant, certains sont résistants à ces traitements ou rechutent à distance justifiant l’intérêt de rechercher de nouvelles cibles thérapeutiques afin d’améliorer l’arsenal thérapeutique du pemphigus. Les résultats de ce travail suggèrent l’implication de CD83 dans l’activité du pemphigus. CD83 est une protéine de la superfamille des immunoglobulines existant sous une forme membranaire, exprimée par un large panel de cellules immunitaires activées, et sous un forme soluble. CD83 joue un rôle particulièrement important dans l’orchestration des réponses immunitaires et dans la régulation de l’auto-immunité. CD83 est notamment impliqué dans la maturation des LB. Nos travaux mettent en évidence que les LB de patients ayant un pemphigus actif ont une transcription plus importante du gène de CD83 en comparaison aux donneurs sains, notamment les LB Dsg3+-spécifiques lors de l’étude par single-cell RNA sequencing. Cette augmentation de transcription est associée à une augmentation de l’expression de CD83 à la membrane des LB et à une baisse du taux de CD83 soluble sérique, qui est corrélé négativement au taux d’anticorps anti-Dsg3, chez les patients ayant un pemphigus actif en comparaison aux donneurs sains et aux patients en rémission. Les LB présents au sein de structures ectopiques lymphocytaires des tissus lésés de pemphigus expriment CD83. En culture de PBMC de pemphigus actif allostimulées ou non stimulées, le traitement par anticorps anti-CD83 est responsable d’une surexpression de CD86 par les LB, d’une augmentation de la production de IgG, d’une plus grande quantité d’anticorps anti-Dsg3, associé à une baisse du CD83 soluble. L’ensemble de ces résultats suggère ainsi un potentiel intérêt thérapeutique à cibler CD83 dans le pemphigus. Alors que de tels traitements sont déjà en développement dans les hémopathies, le rejet de greffe ou des maladies inflammatoires chroniques, un traitement déplétant les LB CD83+ ou administrant du CD83 soluble pourrait permettre d’améliorer la régulation de l’auto-immunité dans le pemphigu.Pemphigus is a heterogeneous group of autoimmune intraepithelial bullous diseases in which B cells produce pathogenic autoantibodies that are directly responsible for bullous and erosive skin and mucosal lesions. Targeted therapies that deplete B lymphocytes (LB) such as anti-CD20 monoclonal antibodies (RTX) have greatly improved the prognosis of patients. However, some patients are resistant to these treatments or relapse at a distance, justifying the interest in searching for new therapeutic targets to improve the therapeutic arsenal of pemphigus. The results of this work suggest the involvement of CD83 in the activity of pemphigus. CD83 is a protein of the immunoglobulin superfamily that exists in a membrane form, expressed by a wide range of activated immune cells, and in a soluble form. CD83 plays a particularly important role in the orchestration of immune responses and in the regulation of autoimmunity. In particular, CD83 participates in the maturation of B-cells. Our work shows that LBs from patients with active pemphigus have a higher transcription of the CD83 gene compared to healthy donors, especially Dsg3+-specific B-cells when studied by single-cell RNA sequencing. This increase in transcription is associated with an increase in membrane CD83 expression in LB and a decrease in serum soluble CD83 levels, which correlate negatively with anti-Dsg3 antibody levels, in patients with active pemphigus compared to healthy donors and patients in remission. LB within lymphocytic ectopic structures of inflamed pemphigus tissue express CD83. In cultured allostimulated or unstimulated active pemphigus PBMCs, treatment with anti-CD83 antibodies resulted in overexpression of CD86 by B-cells, increased IgG production, increased anti-Dsg3 antibodies, and decreased soluble CD83. Together, these results suggest a potential therapeutic interest in targeting CD83 in pemphigus. While such treatments are already in development for hemopathies, graft rejection or chronic inflammatory diseases, a treatment that depletes CD83+ B-cells or administers soluble CD83 might improve the regulation of autoimmunity in pemphigus

Infections humaines à poxvirus

Poxvirus (PXV) infections are a common cause of cutaneous signs. In France, certain forms of poxvirus are frequent and benign (molluscum contagiosum), while others are rare but potentially serious (cowpox virus [CPXV]). Whereas only smallpox and molluscum contagiosum viruses have a human reservoir and are transmitted between humans, most poxvirus infections are zoonoses having only animal reservoirs. Only a small number of poxviruses are responsible for infection in humans, but the increasing number of new pets, some of which are exotic, coupled with the rapid rise in international travel are creating a greater risk of transmission of zoonotic PXV to new vectors and of spread of these diseases to new regions throughout the world. In France, molluscum contagiosum, orf and milkers’ nodule give rise to numerous consultations and are well known to dermatologists. However, dermatologists must also be able to identify other parapoxviruses of similar presentation to orf; thus, CPXV and monkeypox are considered potentially emergent viruses with a high risk of epidemic and spread due to increasing international transport and the loss of the maximum protection against smallpox. Finally, despite its declared eradication, smallpox is currently being monitored because of the potential risk of reintroduction, whether accidentally or deliberately through bioterrorism

Anomaly Detection Algorithm for Acoustics Phenomena

International audienceThe evolution of technologies in call centers towards communications via ethernet is at the origin of a certain number of perturbations. These perturbations can take different forms but the most important one is the acoustic phenomena. In this paper, we present an anomaly detection algorithm based on the One-Class Support Vector Machines (OC-SVM), for the detection of these acoustic phenomena. We are exploring different feature functions and seeking to find the best pairing with the OC-SVM to most effectively detect those acoustic problems that may pose a risk to consultants. Our experimental results show a good detection rate for amplitude levels equal or higher than-15 dB

Shrinking Regions à l'Ouest de l'Europe La Bretagne : un contre-exemple ?

L'intérêt du cas breton est avant tout méthodologique. Quelque soient les tendances démographiques et les projections de population, la Bretagne n'est pas confrontée à la décroissance démographique à l'échelon régional. Il est en revanche possible de disposer de données démographiques à un échelon géographique fin (communes) ainsi que de séries temporelles longues (100 ans) permettant d'aller au-delà des résultats démontrés au niveau des régions européennes. Leurs analyses mettent en évidence une vaste poche de vieillissement et de dépeuplement située dans le centre de la région. Ces changements ne sont pas sans conséquences sur la répartition des services de santé et leurs accessibilités

Recurrent Subcutaneous Phaeohyphomycosis Due to <i>Medicopsis romeroi</i>: A Case Report in a Dermatomyositis Patient and Review of the Literature

Medicopsis romeroi phaeohyphomycosis is increasingly reported in immunocompromised patients living in or originating from tropical and subtropical areas. We report a case of subcutaneous phaeohyphomycosis caused by M. romeroi in a 56-year-old Malian woman residing in France for 20 years. She developed a small nodule on her dominant hand’s ring finger 15 months after starting immunosuppressive medications for paraneoplastic dermatomyositis. A first surgical debridement was followed by a local recurrence. Despite a second surgical excision combined with posaconazole treatment, the infection recurred one year after antifungal therapy discontinuation. A wide excision was performed again, and antifungal therapy was resumed and maintained for six months, resulting in the absence of relapse during the 18 months following the surgery. This case highlighted the high risk of relapse in immunocompromised patients, suggesting the need for long-term follow-up and prolonged antifungal treatment following surgical excision in cases with sustained immunosuppression. The literature review was performed according to PRISMA guidelines and included 51 scientific publications. A noteworthy predominance of the subcutaneous phaeohyphomycosis presentation was found in immunocompromised patients, whereas eumycetoma had been reported in apparently healthy individuals. A combination of complete excision with antifungal treatment seemed to confer the best outcome

Impaired social cognition and fine dexterity in patients with Cowden syndrome associated with germline PTEN variants

International audiencePurpose: Cowden syndrome (CS) is an autosomal dominant disease related to germline PTEN variants and is characterised by multiple hamartomas, increased risk of cancers and frequent brain alteration. Since the behaviour of patients with CS sometimes appears to be inappropriate, we analysed their neuropsychological functioning.Methods: This monocentric study was conducted between July 2018 and February 2020. A standardised neuropsychological assessment, including an evaluation of social cognition, executive functions, language and dexterity, as well as a cerebral MRI were systematically proposed to all patients with CS. Moreover, PTEN variants were identified.Results: Fifteen patients from 13 families were included, with six non-sense (40%), three missense (20%), five frameshift (33.3%) and one splice site (6.6%) variant types. Twelve patients (80%) had altered social cognition: 10 patients had an abnormal modified Faux-Pas score and 5 had Ekman's facial emotions recognition impairment. Nearly all patients (93%) had impaired dexterity. Cerebral MRI showed various cerebellar anomalies in seven patients (46.7%).Conclusion: Altered social cognition and impaired fine dexterity are frequently associated with CS. Further studies are needed to confirm these results and to determine whether dexterity impairment is due to the effect of germline PTEN variants in the cerebellum

Cutaneous Involvement in Waldenström's Macroglobulinaemia.

Cutaneous involvement in Waldenström's macroglobulinaemia (WM) has been poorly characterized. To describe this involvement, a retrospective study of 19 patients with WM and cutaneous involvement of tumour B cells was performed. Twelve patients (group 1) had lymphoplasmacytic, non-transformed cutaneous proliferation, while in 7 cases (group 2) cutaneous involvement corresponded to histological transformation. In group 1, skin involvement was inaugural in 6 cases. The lesions were infiltrated plaques (83%), papules (25%) and tumours (42%). Four patients had a similar clinical picture (purplish, bilateral and symmetrical infiltration on the face). MYD88 L265P mutation was detected in the skin biopsy in all 6 cases tested. The 3-year specific survival rate was 88%. In group 2, cutaneous transformation occurred during the follow-up of the WM (71%). Lesions presented as ulcerated tumours (86%) of the trunk (57%) and lower limbs (57%). The 3-year specific survival rate was 22%. Skin involvement in WM has distinctive characteristics (e.g. clinical, histological, immunohistochemical, MYD88 L265P mutation)