Desmoglein 3

While classic cadherin-actin connections in adherens junctions (AJs) have ancient origins, intermediate filament (IF) linkages with desmosomal cadherins arose in vertebrate organisms. In this mini-review, we discuss how overlaying the IF-desmosome network onto the existing cadherin-actin network provided new opportunities to coordinate tissue mechanics with the positioning and function of chemical signaling mediators in the ErbB family of receptor tyrosine kinases. We focus in particular on the complex multi-layered outer covering of the skin, the epidermis, which serves essential barrier and stress sensing/responding functions in terrestrial vertebrates. We will review emerging data showing that desmosome-IF connections, AJ-actin interactions, ErbB family members, and membrane tension are all polarized across the multiple layers of the regenerating epidermis. Importantly, their integration generates differentiation-specific roles in each layer of the epidermis that dictate the form...

Cell aggregation is frequently impaired during the growth of primary tumors and the formation of metastatic lesions. Cell aggregation depends on cell-cell adhesion; however, no rigorous approach exists to monitor and quantify it accurately in the absence of the confounding factors of cell-substrate adhesion and the resulting cell motility on the substrate. We report here a highly reproducible, automated, microscopy-based quantification of tumor-cell spheroid formation in the absence of cellsubstrate adhesion and use it to characterize cell aggregation dynamics in the early steps of this process. This method is based on fluorescence and bright-field microscopy and on a custom MATLAB program to quantify automatically the cells' aggregation kinetics. We demonstrate that the cell-cell adhesion protein E-cadherin and the desmosome proteins DSG2 and DSC2 are important for aggregation. Furthermore, we show that inhibition or silencing of myosin IIa enhances aggregation, suggesting that cytoskeleton tension inhibits tumor cell aggregation. This work opens new avenues to study the principles that govern multicellular aggregation, to characterize the aggregation properties of various tumor cell types, as well as to screen for drugs that inhibit or promote aggregation. Cancer Res; 75(12); 2426-33. Ó2015 AACR.

Cell aggregation is frequently impaired during the growth of primary tumors and the formation of metastatic lesions. Cell aggregation depends on cell-cell adhesion, however, no rigorous approach exists to monitor and quantify it accurately in the absence of the confounding factors of cell-substrate adhesion and the resulting cell motility on the substrate. We report here a highly reproducible, automated, microscopy-based quantification of tumor cell spheroid formation in the absence of cell-substrate adhesion and use it to characterize cell aggregation dynamics in the early steps of this process. This method is based on fluorescence and bright-field microscopy and on a custom MATLAB program to quantify automatically the cells' aggregation kinetics. We demonstrate that the cell-cell adhesion protein E-cadherin and the desmosome proteins DSG2 and DSC2 are important for aggregation. Futhermore, we show that inhibition or silencing of myosin IIa enhances aggregation, suggesting that...

Paraneoplastic pemphigus (PNP) is an autoimmune blistering disease that occurs in association with underlying neoplasms. Patients with PNP develop characteristic IgG autoantibodies directed against multiple antigens, most of which have been identified as cytoplasmic proteins of the plakin family (desmoplakin I, II, BPAG1, envoplakin, and periplakin). This study identified cell surface target antigens of PNP. We focused on desmoglein (Dsg) 3 and Dsg1, the autoantigens of pemphigus vulgaris and pemphigus foliaceus. ELISA using baculovirus-expressed recombinant Dsgs (rDsg3, rDsg1) has revealed that 25 out of 25 PNP sera tested were positive against Dsg3 and 16 of 25 were positive against Dsg1. All of 12 PNP sera tested immunoprecipitated Dsg3. Removal of anti-Dsg3 autoantibodies by immunoadsorption was sufficient to eliminate the ability of PNP sera to induce cutaneous blisters in neonatal mice in vivo. Furthermore, anti-Dsg3-specific antibodies that were affinity purified from PNP sera were proven to be pathogenic and caused blisters in neonatal mice. These findings indicate that Dsg3 and Dsg1 are the cell surface target antigens in PNP and that IgG autoantibodies against Dsg3 in PNP sera play a pathogenic role in inducing loss of cell adhesion of keratinocytes and causing blister formation. (

Pemphigus foliaceus (PF) and the endemic form Fogo Selvagem (FS) are mediated by pathogenic antibodies to the EC1-2 domains of desmoglein-1. There is a preclinical phase with antibodies to only EC5. Based on geographic clustering of cases, FS is thought to have an, as yet unidentified, environmental trigger. In this study we have searched for anti-desmoglein-1 antibodies in sera from parasitic (leishmaniasis, Chagas, and onchocerciasis), and infectious diseases (leprosy and South American (SA) blastomycosis), which are prevalent in the same geographic regions of Brazil as FS. A specific and sensitive desmoglein-1 ELISA detected antibodies in 34 of 41 onchocerciasis (83%), 38 of 88 leishmaniasis (43%), 18 of 31 Chagas disease (58%), 7 of 28 SA blastomycosis (25%), and 14 of 83 leprosy sera (17%). These sera recognized epitopes restricted to the EC5 domain. These findings identify several etiological factors for FS. It is hypothesized that a component of insect vector saliva, rather than the parasite itself may trigger an antibody response to EC-5. In persons with the known HLA susceptibility alleles and living in endemic areas, a response to the EC1-2 domains may subsequently develop by epitope spreading with associated clinical signs of FS.

Background Pemphigus is a rare but life-threatening autoimmune skin disease characterized by blistering on skin and/or mucous membranes. The physiological process of blister formation involves IgG antibodies against the desmogleins (Dsgs) and desmocollins (Dscs). Additional autoAbs have also been suggested to mediate the disease heterogeneity, such as anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies, the essential culprits of the immune system in autoimmune thyroid diseases. Purpose To investigate the levels and antibody positivity of anti-TPO and anti-Tg antibodies in pemphigus patients. Methods Antibody positivity and levels of anti-TPO and anti-Tg antibodies in pemphigus patients as compared to healthy controls were examined. A meta-analysis was conducted by reviewing six similar studies. Results 98 Chinese pemphigus patients and 65 healthy controls were enrolled in the study. Our meta-analysis revealed a significant correlation between increased pres...

The environmental factors that contribute to the development of autoimmune diseases are largely unknown. Endemic pemphigus foliaceus in humans, known as Fogo Selvagem (FS) in Brazil, is mediated by pathogenic IgG4 autoantibodies against desmoglein 1 (Dsg1). Clusters of FS overlap with those of leishmaniasis, a disease transmitted by sand fly (Lutzomyia longipalpis) bites. In this study, we show that salivary Ags from the sand fly, and specifically the LJM11 salivary protein, are recognized by FS Abs. Anti-Dsg1 monoclonal autoantibodies derived from FS patients also cross-react with LJM11. Mice immunized with LJM11 generate anti-Dsg1 Abs. Thus, insect bites may deliver salivary Ags that initiate a cross-reactive IgG4 Ab response in genetically susceptible individuals and lead to subsequent FS. Our findings establish a clear relationship between an environmental, noninfectious Ag and the development of potentially pathogenic autoantibodies in an autoimmune disease.

The endemic form (fogo selvagem-FS) of pemphigus foliaceus is an autoimmune disease characterized by the presence of IgG autoantibodies against desmoglein-1. Despite the array of findings, the role of chemokines and cytokines that dictate the immune response and disease outcome is still poorly investigated. Serum from 64 patients diagnosed with FS was used to draw and establish the levels of these molecules on this disease and establish the levels of these molecules with the severity of FS, and influence of treatment. In comparison to healthy subjects, FS patients, newly diagnosed and still without therapeutic intervention, had higher levels of IL-22 and CXCL-8, and reduced levels of IFN-γ, IL-2, IL-15, and CCL-11. Furthermore, treatment using immunosuppressant drugs augmented the production of IFN-γ, IL-2, CCL-5, and CCL-11 besides reducing the levels of IL-22 and CXCL-10. Immunosuppressive therapy seemed to have long-lasting effects on the production of higher amounts of IFN-γ, IL...

Background: Black fly and sandfly bites are related to the endemicity of pemphigus foliaceus (PF); however, an immune reaction against the salivary proteins from these flies still requires confirmation in the case of PF patients living in southeastern Brazil. Purpose: To georeference the distribution of Simuliidae (Diptera: Simuliidae) and Phlebotominae (Diptera: Psychodidae) and of PF cases in the northeastern region of São Paulo State, and to assess the humoral immune response against salivary gland extracts (SGEs) from biting flies in PF patients, relatives, and neighbours. Methods: PF patients' medical information recorded between 1965 and 2014 were obtained from the database of the University Hospital. Data on the distribution of fly species were collected from scientific reports and epidemiological databases. Spatial maps relating the distribution of biting flies with PF cases were plotted. Serum IgG antibodies against the SGEs from Simulium nigrimanum, Nyssomyia neivai, and Aedes aegypti (as control) were determined by ELISA. Results: Two hundred and eighty-five PF cases were distributed in 60 municipalities with a prevalence of 57.5 per million inhabitants, revealing well-defined geographical clusters. S. nigrimanum and N. neivai specimens were registered in eight (13.3%) and 26 (43.3%) of these municipalities, respectively. PF patients, and their relatives presented higher levels of IgG against the SGEs of S. nigrimanum and N. neivai (P < 0.001 for both), but not against the SGE from A. aegypti (P=0.115 and P=0.552, respectively), as compared to controls. IgG against the SGEs from S. nigrimanum and N. neivai but not against the SGE from A. aegypti correlated with levels of anti-Desmoglein 1 in PF patients (r=0.3848, P=0.039; and r=0.416, P=0.022, respectively). Conclusion: An epidemiological link between biting flies and PF in southeastern Brazil is proposed, implying a possible role of the salivary proteins from these flies in PF etiopathogenesis.

Background: Pemphigus is an autoimmune blistering disease of the skin and mucous membranes caused by autoantibodies against desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3). Pemphigus vulgaris (PV) is the most common form of pemphigus. The aim of this study was to assess the correlation between the levels of anti-desmoglein 1 and 3 autoantibodies and the severity of PV disease. Material and Methods: Nineteen newly diagnosed patients with pemphigus vulgaris were enrolled in this study. The titers of Dsg in subjects by using enzyme-linked immunosorbent assay (ELISA) were done at diagnosis time-point, 4th and 8th weeks after the initiation of treatment, and the correlation of antibodies with the oral and skin disease severity was evaluated. Results: The severity of cutaneous lesions was significantly correlated with anti-Dsg1 titer in all visits and the severity of mucosal lesions was correlated with the titer of Dsg3 in the third visit (<0.001, 0.001, 0.016 and 0.015 P value, respectively). Conclusions: Anti-Dsg-1 autoantibodies titers seem to be more useful in showing the extent of the disease and activity in pemphigus with mucocutaneous lesions.

Serum antibodies against desmoglein 1 (Dsg1) are known to induce the clinical and histological manifestations of pemphigus foliaceus (PF), autoimmune bullous disease targeting skin. The basic pathophysiological phenomenon of PF blistering is the disruption of epithelial integrity in the granular layer of the epidermis due to separation of keratinocytes from one another, or acantholysis. In this report we investigate the changes in subcellular distribution of Dsg1 in response to serum of patients with PF by using an in vitro model of PF. Immunofluorescence analysis on HaCaT cells indicates that non-clustered Dsg1 is markedly internalized after exposure to serum. However, binding of PF IgG to Dsg1-rich adhesion complexes (desmosomes) does not cause disruption of such structures nor depletion of clustered Dsg1, as revealed by colocalization of PF IgG and Dsg1 in a punctate staining on cell membrane 24 hours after treatment. Furthermore, morphological studies demonstrate that the dramat...

Pemphigus vulgaris (PV) is a life-long, potentially fatal IgG autoantibody-mediated blistering disease targeting mucocutaneous keratinocytes (KCs). PV patients develop pathogenic anti-desmoglein (Dsg) 3 ± 1 and anti-mitochondrial antibodies (AMA), but it remained unknown if and how AMA enter KCs and why other cell types are not affected in PV. Therefore, we sought to elucidate mechanisms of cell entry, trafficking and pathogenic action of AMA in PV. We found that PVIgGs associated with FcRn on the cell membrane, the PVIgG-FcRn complexes entered KCs, and reached mitochondria where they dissociated. The liberated AMA altered mitochondrial membrane potential, respiration, ATP production, and induced cytochrome c release, while the lack or inactivation of FcRn abolished the ability of PVIgG to reach and damage mitochondria, and to cause detachment of KCs. The assays of mitochondrial functions and keratinocyte adhesion demonstrated that while the pathobiological effects of AMA on KCs are...

A loss of epidermal cohesion in pemphigus vulgaris (PV) results from autoantibody action on keratinocytes (KCs) activating the signaling kinases and executioner caspases that damage KCs, causing their shrinkage, detachment from neighboring cells, and rounding up (apoptolysis). In this study, we found that PV antibody binding leads to activation of epidermal growth factor receptor kinase, Src, p38 MAPK, and JNK in KCs with time pattern variations from patient to patient. Both extrinsic and intrinsic apoptotic pathways were also activated. Although Fas ligand neutralizing antibody could inhibit the former pathway, the mechanism of activation of the latter remained unknown. PV antibodies increased cytochrome c release, suggesting damage to mitochondria. The immunoblotting experiments revealed penetration of PVIgG into the subcellular mitochondrial fraction. The antimitochondrial antibodies from different PV patients recognized distinct combinations of antigens with apparent molecular sizes of 25, 30, 35, 57, 60, and 100 kDa. Antimitochondrial antibodies were pathogenic because their absorption abolished the ability of PVIgG to cause keratinocyte detachment both in vitro and in vivo. The downstream signaling of antimitochondrial antibodies involved JNK and late p38 MAPK activation, whereas the signaling of anti-desmoglein 3 (Dsg3) antibody involved JNK and biphasic p38 MAPK activation. Using KCs grown from Dsg3 ؊/؊ mice, we determined that Dsg3 did not serve as a surrogate antigen allowing antimitochondrial antibodies to enter KCs. The PVIgG-induced activation of epidermal growth factor receptor and Src was affected neither in Dsg3 ؊/؊ KCs nor due to absorption of antimitochondrial antibodies. These results demonstrated that apoptolysis in PV is a complex process initiated by at least three classes of autoantibodies directed against desmosomal, mitochondrial, and other keratinocyte self-antigens. These autoantibodies synergize with the proapoptotic serum and tissue factors to trigger both extrinsic and intrinsic pathways of cell death and break the epidermal cohesion, leading to blisters. Further elucidation of the primary signaling events downstream of PV autoantigens will be crucial for the development of a more successful therapy for PV patients.

The reduction or loss of plakoglobin expression in late-stage bladder cancer has been correlated with poor survival where upregulation of this catenin member by histone deacetylase inhibitors has been shown to accompany tumour suppression in an in vivo model. In this study, we directly addressed the question of the role of plakoglobin in bladder tumorigenesis following restoration, or knockdown of expression in bladder carcinoma cell lines. Restoration of plakoglobin expression resulted in a reduction in migration and suppression of tumorigenic potential in vivo. Immunocytochemistry revealed cytoplasmic and membranous localisation of plakoglobin in transfectants with o1% of cells displaying detectable nuclear localisation of plakoglobin. siRNA knockdown experiments targeting plakoglobin, revealed enhanced migration in all cell lines in the presence and absence of E-cadherin expression. In bladder cell lines expressing low levels of plakoglobin and desmoglein-2, elevated levels of desmoglein-2 were detected following restoration of plakoglobin expression in transfected cell lines. Analysis of wnt signalling revealed no activation event associated with plakoglobin expression in the bladder model. These results show that plakoglobin acts as a tumour suppressor gene in bladder carcinoma cells and the silencing of plakoglobin gene expression in late-stage bladder cancer is a primary event in tumour progression.

In pemphigus vulgaris, a life-threatening autoimmune skin disease, epidermal blisters are caused by autoantibodies primarily targeting desmosomal cadherins desmoglein 3 (DSG3) and DSG1, leading to loss of keratinocyte cohesion. Due to limited insights into disease pathogenesis, current therapy relies primarily on nonspecific long-term immunosuppression. Both direct inhibition of DSG transinteraction and altered intracellular signaling by p38 MAPK likely contribute to the loss of cell adhesion. Here, we applied a tandem peptide (TP) consisting of 2 connected peptide sequences targeting the DSG adhesive interface that was capable of blocking autoantibody-mediated direct interference of DSG3 transinteraction, as revealed by atomic force microscopy and optical trapping. Importantly, TP abrogated autoantibody-mediated skin blistering in mice and was effective when applied topically. Mechanistically, TP inhibited both autoantibody-induced p38 MAPK activation and its association with DSG3, abrogated p38 MAPK-induced keratin filament retraction, and promoted desmosomal DSG3 oligomerization. These data indicate that p38 MAPK links autoantibody-mediated inhibition of DSG3 binding to skin blistering. By limiting loss of DSG3 transinteraction, p38 MAPK activation, and keratin filament retraction, which are hallmarks of pemphigus pathogenesis, TP may serve as a promising treatment option.

In the human autoimmune blistering skin disease pemphigus vulgaris autoantibodies (PV-IgG), which are mainly directed against keratinocyte cell adhesion molecules desmoglein (Dsg) 3 and Dsg1, cause keratinocyte cell dissociation (acantholysis). Recent studies reported that loss of keratinocyte cell adhesion was accompanied by profound alterations of the actin cytoskeleton. Nevertheless, the relevance of actin reorganization in this process is unclear at present. In this study, we provide evidence for an important role of actin reorganization in pemphigus pathogenesis. In parallel to loss of cell adhesion and fragmentation of Dsg3 staining along cell borders, PV-IgG treatment resulted in striking changes in actin cytoskeleton organization. Moreover, in experiments using fluorescence recovery after photobleaching (FRAP), PV-IgG were detected to interfere with actin dynamics. Therefore, we investigated whether pharmacological manipulation of actin polymerization modulates pathogenic ef...

Background. Serum desmoglein enzyme-linked immunosorbent assay (ELISA) is used for the diagnosis and monitoring of pemphigus diseases.Objectives. To compare the diagnostic accuracy of salivary antidesmoglein (Dsg) 1 and 3 ELISA in the diagnosis of pemphigus vulgaris (PV) patients with that of serum desmogleins ELISA.Methods. Eighty-six untreated PV patients and 180 age- and sex-matched PV-free controls were recruited in this case-control study. PV was diagnosed based on clinical, histopathological, and direct immunofluorescence findings. After processing, serum and salivary anti-Dsg 1 and 3 were measured by the ELISA method using Euroimmun kit (Lübeck, Germany).Results. Using the cut-off point of 20 relative units (RU)/mL, the serum anti-Dsg 1 and 3 ELISA were positive in 62 (72.1%) and 83 (96.5%) patients, respectively, and the salivary anti-Dsg 1 and 3 ELISA were positive in 31 (36.1%) and 63 (73.3%) patients, respectively. The specificity of salivary anti-Dsg 1 and anti-Dsg 3 wer...

Antibodies against desmoglein proteins account for intraepidermal immunobullous disorders in the pemphigus family of diseases. Antibodies against desmoglein 3 are responsible for the blisters seen in patients with pemphigus vulgaris, whereas antibodies against desmoglein 1 lead to the more superficial separation seen in pemphigus foliaceus. Similar in both clinical and histologic features to pemphigus foliaceus (PF), an endemic form of the disease, fogo selvagem (FS) is found in high prevalence in certain regions of Brazil (Diaz et al., 1989). The endemic nature of the condition is thought to be precipitated by an immune response to an environmental antigen(s), currently not yet identified. This unique epidemiologic phenomenon provides researchers with an opportunity to study the differences between endemic and sporadic forms of this disease. In this issue of the Journal, studied early immunologic responses among patients with FS to determine whether the IgM response differs from that seen in patients with the sporadic disease. In a comprehensive assessment of immune responses, they evaluated sera from patients with FS in rural endemic and urban areas of Brazil, patients with PF in the United States and Japan, and control subjects in these locations. Detection of desmoglein 1 IgM varied, with the highest levels (58%) in FS patients in endemic regions and control subjects (>50%) from the same areas. The desmoglein 1 IgM response was considerably lower (12-18%) in FS patients from urban areas of Brazil and still lower in patients from the United States (10%) and Japan (0%). Less variability was found in IgG responses in patients, with markedly lower responses in control subjects, apart from control subjects from rural areas of Brazil. The investigators hypothesize that an environmental agent responsible for the development of FS may cause an early IgM response that predates clinical disease. Through the following questions we will examine this paper in greater detail. For brief answers please refer to .

To determine the distribution of cell membrane proteins and extracellular matrix proteins around the limbal epithelial crypt (LEC) compared with adjacent limbus and corneal epithelium. Methods: Serial histological sections of human corneoscleral limbus rims were stained with antibodies of interest by standard immunohistochemistry.

Anchorage of the hair to its follicle is of paramount importance for survival of rodents in the wild, and is aberrant in some human alopecias. Little is understood about the mechanisms responsible for hair shaft anchorage. Desmoglein (Dsg)3À/À (knockout) mice lose hair during telogen, but their anagen hairs remain anchored to the follicle. We hypothesized that Dsg1 compensates for the loss of Dsg3 in the anagen hair follicles of these Dsg3À/À mice. Consistent with this hypothesis, we found Dsg1 and Dsg3 expression overlapping in the companion layer. To functionally address this hypothesis, we used exfoliative toxin A (ETA) to inactivate Dsg1 in Dsg3À/À mice. Four hours after injection of ETA, Dsg3À/À mice, but not Dsg3 þ / þ or Dsg3 þ /À mice, showed striking loss of anagen hair, which was confirmed and quantitated by gentle tape stripping. Histology of the skin of these mice as well as of the tape-stripped hair showed separation between the outer root sheath and inner root sheath of the hair follicle, at the plane of the companion layer. Immunostaining for trichohyalin and K6, which highlights the companion layer, in skin and stripped hair confirmed the plane of separation. Labeling of proliferating cells with bromodeoxyuridine demonstrated that the matrix keratinocytes responsible for producing the hair shaft were below the split and remained in the follicle after loss of the anagen hair. These findings demonstrate the importance of the companion layer, and particularly the Dsg1 and Dsg3 in this layer, in anchoring the anagen hair to the follicle.

The simultaneous occurrence of HIV-related immunodeficiency and autoimmune diseases is clearly documented. This cross-sectional study including 594 HIV-infected patients and 248 healthy controls lacking signs of autoimmune blistering skin diseases evaluated the frequency, titres and combinational appearance of autoantibodies directed against BP180, BP230, desmoglein 1 and 3, and showed no differences between the 2 patient groups. Interestingly, reactive syphilis serology in both HIV-infected individuals and uninfected controls was associated with positive anti-BP180 ELISA results, prompting a further evaluation for syphilis antibodies in patients with positive BP180 ELISA results and no clinical signs of bullous pemphigoid. Various autoantibodies are detected more frequently in HIV-infected individuals than in HIV-negative controls; however, limited data exist regarding autoimmune blistering skin diseases. Using enzyme-linked immunoassay (ELISA) and indirect immunofluore scence, no difference in the frequency and magnitude of autoantibodies against BP180, BP230, desmoglein 1 and 3 was found between 594 HIV-infected patients and 248 uninfected controls in this cross-sectional study (16.0% vs. 11.7%, respectively, for at least one positive ELISA, p = 0.11). Interestingly, reactive syphilis serology in both HIV-infected individuals and uninfected controls was associated with positive anti-BP180 ELISA results (adjusted odds ratio (OR) 2.14, 95% confidence interval (CI) 1.07-4.29, p = 0.03 and OR 4.70, CI 1.3-16.86; p = 0.0180). Our study shows a comparably low prevalence of cutaneous autoantibodies in both HIV-infected patients and uninfected controls lacking signs of autoimmune blistering skin disease. Positive BP180 ELISA in the absence of clinical signs of bullous pemphigoid should prompt further evaluation for syphilis antibodies.

Mucosal associated invariant T (MAIT) cells are innate like lymphocytes found in peripheral blood and mucosa; they are decreased during systemic lupus erythematosus and other autoimmune diseases. However, MAIT cell levels and functions have not previously been investigated in dermatomyositis (DM). Herein, we studied MAIT cells level and activation status before and after treatment during DM (n¼21) and compared them to healthy controls (n¼19), psoriasis (n¼7) and atopic dermatitis (n¼5). We showed that DM was associated with a dramatic reduced number of circulating MAIT cells (median: 0.12% [0.073-0.25%] versus 2.13% [1.05-3.94%], p < 0.0001). This disappearance was specific to DM. Residual MAIT cells displayed an activated/exhausted phenotype with higher expression of CD25, CD39, CTLA4 and increase of the TEMRA state. We found an inverse correlation between CD25 and CTLA4 expression on MAIT cells and the level of circulating MAIT cells. After a median follow up of 0.9 year, we observed a slight increase of MAIT cells (median: 0.25% [0.24-0.60%] versus 0.73% [0.47-1.16%], p ¼ 0.002). Nevertheless, it did not return to normal healthy controls level. We next compared skin from DM with healthy controls for PLZF, the master transcript of MAIT cells thanks to microarray analysis. PLZF was not elevated in lesional skin. Finally, preliminary in vitro assays showed that strong stimulation by both TCR and IL-12 and IL-18, cytokines elevated during DM and known to activate MAIT cells, leaded to decreased expression of CD161 and higher mortality. Taken together, our data indicate that in DM peripheral blood MAIT cells, which are thought to have regulatory role, are dramatically reduced in relationship with an activated abnormal phenotype potentially leading to activation induced cell death rather than their migration in affected tissue.

It is hypothesized that SARS-CoV-2 has the potential to elicit autoimmunity due to molecular mimicry between immunogenic proteins of the virus and human extracellular molecules. While in silico and in vitro evaluation of such immune cross-reactivity of human antibodies to SARS-CoV-2 proteins with several different tissue antigens has been described, there is limited information specifically pertaining to the immunological effects of COVID-19 and vaccines against SARS-CoV-2 on the development of autoimmune bullous diseases (AIBDs). Twelve seropositive post-COVID-19 individuals and 12 seropositive healthy volunteers who received two doses of the mRNA COVID-19 vaccine from Pfizer-BioNTech have been included in this case series investigation. Serum samples of these blood donors were tested for autoantibodies to the main immunobullous autoantigens, i.e., desmoglein 1, desmoglein 3, envoplakin, BP180, BP230, and type VII collagen. Our study revealed that none of the 24 anti-SARS-CoV-2 IgG...

Background: Lichenoid reaction (LR) is a relatively common mucocutaneous disease with an unknown etiology. Since the cause of the LRs is unknown, many drugs have been studied to palliate the symptoms. Previous studies reported that corticosteroids are often effective in the management of several oral inflammatory diseases. The aim of the present study was to compare the effect of Melissa gel and triamcinolone 0.1% paste on clinical indices of oral LRs. Materials and Methods: In this randomized clinical trial, sixty patients with erosive oral LRs were randomly divided into two groups, and each group was treated with Melissa gel or triamcinolone acetonide 0.1% paste, three times a day, for 4 weeks. The recovery rate and severity of pain and burning sensation were assessed after 2 and 4 weeks. Finally, the obtained data were analyzed using SPSS software (version 20, IBM Corp., Armonk, NY, USA) and repeated measures ANCOVA, Mann-Whitney test, Chi-square test, paired t-test, and survival analysis.(α = 0.05). Results: The Visual Analog Scale scores for recovery rate, pain, and burning mouth sensation and objective scoring for oral lichen planus were significantly improved at 2 and 4 weeks in both the groups. However, the pain intensity decreased significantly in the Melissa group, as compared to the triamcinolone 1% group. Conclusion: In general, we showed that Melissa gel has a better effect than triamcinolone on pain intensity. Although Melissa gel is effective in reducing lesion size, triamcinolone significantly showed better results.