IgG autoantibodies in bullous pemphigoid directly induce a pathogenic MyD88-dependent pro-inflammatory response in keratinocytes.

Unlabelled: While autoantibodies in bullous pemphigoid (BP) are known to activate the innate immune response, their direct effect on keratinocytes, and the contribution of BP-IgG autoantibody-dependent keratinocyte responses to BP pathology is largely unknown. Herein, we performed multiplex immunoassays and bulk RNA-seq on primary keratinocytes treated with IgG from BP patients or controls. We identified a pro-inflammatory and proteolytic response with release of several cytokines (IL-6, IL-24, TGF-β1), chemokines (CXCL16, CTACK, MIP-3β, RANTES), C1s, DPP4, and MMP-9.

Anti-Laminin β4 IgG Drives Tissue Damage in Anti-p200 Pemphigoid and Shows Interactions with Laminin α3 and γ1/2 Chains.

Laminin β4 was recently identified as a structural component of the dermal-epidermal junction and autoantigen of anti-p200 pemphigoid. In this study, we provided further evidence of the pathogenic effect of anti-laminin β4 IgG and identified potential binding partners of laminin β4. We showed that laminin β4 immune complexes led to activation of normal leukocytes and dose-dependent ROS release.

Risk and timing of isotretinoin-related laboratory disturbances: a population-based study.

Introduction: Uncertainty surrounds the optimal routine laboratory monitoring in acne patients treated with isotretinoin.

Objective: Our aim was to evaluate the risk of mild and severe laboratory abnormalities in patients with acne starting isotretinoin versus oral antibiotic treatment.

Methods: A global population-based retrospective cohort study assigned two groups of patients with acne-prescribed isotretinoin (n = 79,012) and oral antibiotics (n = 79,012).

Anti-BP230 IgE autoantibodies in bullous pemphigoid intraindividually correlate with disease activity.

Background: Bullous pemphigoid (BP), the most common subepidermal autoimmune blistering disease, is classically defined by the presence of IgG autoantibodies directed against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230 and the predominance of skin lesions. Several studies have addressed the role of anti-BP180 IgE in patients and experimental models, while data on anti-BP230 IgE are scarce.

Objective: To assess anti-BP230 IgE level by ELISA in BP sera and to correlate it with disease severity and clinical characteristics.

Laminin β4 is a constituent of the cutaneous basement membrane zone and additional autoantigen of anti-p200 pemphigoid.

Background: Anti-p200 pemphigoid is a subepidermal autoimmune blistering disease (AIBD) characterized by autoantibodies against a 200 kDa protein. Laminin γ1 has been described as target antigen in 70% to 90% of patients. No diagnostic assay is widely available for anti-p200 pemphigoid, which might be due to the unclear pathogenic relevance of anti-laminin γ1 autoantibodies.

Bullous pemphigoid induced by IgG targeting type XVII collagen non-NC16A/NC15A extracellular domains is driven by Fc gamma receptor- and complement-mediated effector mechanisms and is ameliorated by neonatal Fc receptor blockade.

Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by autoantibodies targeting type XVII collagen (Col17) with the noncollagenous 16A (NC16A) ectodomain representing the immunodominant site. The role of additional extracellular targets of Col17 outside NC16A has not been unequivocally demonstrated. In this study, we showed that Col17 ectodomain-reactive patient sera depleted in NC16A IgG induced dermal-epidermal separation in a cryosection model indicating the pathogenic potential of anti-Col17 non-NC16A extracellular IgG.

Mouse models of pemphigus: valuable tools to investigate pathomechanisms and novel therapeutic interventions.

Autoimmune blistering diseases (AIBD) are paradigms of autoantibody-mediated organ-specific autoimmune disorders that involve skin and/or mucous membranes. Compared to other autoimmune diseases, the pathogenicity of autoantibodies in AIBD is relatively well described. Pemphigus is a potentially lethal autoantibody driven autoimmune disorder with a strong HLA class II association.

Corrigendum: Cutaneous kinase activity correlates with treatment outcomes following PI3K delta inhibition in mice with experimental pemphigoid diseases.

[This corrects the article DOI: 10.3389/fimmu.2022.

Cutaneous kinase activity correlates with treatment outcomes following PI3K delta inhibition in mice with experimental pemphigoid diseases.

Chronic blistering at the skin and/or mucous membranes, accompanied by a varying degree of inflammation, is the clinical hallmark of pemphigoid diseases that impose a major medical burden. Pemphigoid diseases are caused by autoantibodies targeting structural proteins of the epithelial basement membrane. One major pathogenic pathway of skin blistering and inflammation is activation of myeloid cells following Fc gamma receptor-dependent binding to the skin-bound immune complexes.

Pathogenic Activation and Therapeutic Blockage of FcαR-Expressing Polymorphonuclear Leukocytes in IgA Pemphigus.

Pathomechanisms in IgA pemphigus are assumed to rely on Fc-dependent cellular activation by antigen-specific IgA autoantibodies; however, models for the disease and more detailed pathophysiologic data are lacking. In this study, we aimed to establish in vitro models of disease for IgA pemphigus, allowing us to study the effects of the interaction of anti-keratinocyte IgA with cell surface FcαRs. Employing multiple in vitro assays, such as a skin cryosection assay and a human skin organ culture model, in this study, we present mechanistic data for the pathogenesis of IgA pemphigus, mediated by anti-desmoglein 3 IgA autoantibodies.

Milestones in Personalized Medicine in Pemphigus and Pemphigoid.

Pemphigus and pemphigoid diseases are autoimmune bullous diseases characterized and caused by autoantibodies targeting adhesion molecules in the skin and/or mucous membranes. Personalized medicine is a new medical model that separates patients into different groups and aims to tailor medical decisions, practices, and interventions based on the individual patient`s predicted response or risk factors. An important milestone in personalized medicine in pemphigus and pemphigoid was achieved by verifying the autoimmune pathogenesis underlying these diseases, as well as by identifying and cloning several pemphigus/pemphigoid autoantigens.

Identification of novel therapeutic targets for blocking acantholysis in pemphigus.

Background And Purpose: Pemphigus is caused by autoantibodies against desmoglein (Dsg) 1, Dsg3, and/or non-Dsg antigens. Pemphigus vulgaris (PV) is the most common manifestation of pemphigus, with painful erosions on mucous membranes. In most cases, blistering also occurs on the skin, leading to areas of extensive denudation.

BP180-specific IgG is associated with skin adverse events, therapy response, and overall survival in non-small cell lung cancer patients treated with checkpoint inhibitors.

Background: Anti-programmed cell death protein 1 (PD1)/programmed death-ligand 1(PD-L1) therapy frequently entails immune-related adverse events (irAEs), and biomarkers to predict irAEs are lacking. Although checkpoint inhibitors have been found to reinvigorate T cells, the relevance of autoantibodies remains elusive.

Objective: Our aim was to explore whether IgG autoantibodies directed against coexpressed antigens by tumor tissue and healthy skin correlate with skin irAEs and therapy outcome.

Translational Use of a Standardized Full Human Skin Organ Culture Model in Autoimmune Blistering Diseases.

The full human skin organ culture (HSOC) model is a standardized test system for evaluating pharmacological substances on human skin in vitro. The acantholysis associated with pemphigus vulgaris (PV), a severe and potentially life-threatening autoimmune skin blistering disease, can be induced in HSOC by injecting a bi-specific anti-desmoglein (dsg) 1 and 3 single-chain antibody variable fragment (scFv). Compared to cell culture experiments (e.

Immunoadsorption of Desmoglein-3-Specific IgG Abolishes the Blister-Inducing Capacity of Pemphigus Vulgaris IgG in Neonatal Mice.

Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune blistering disease which is associated with autoantibodies directed against two desmosomal proteins, desmoglein (Dsg) 3 and 1. Treatment of PV is rather challenging and relies on the long-term use of systemic corticosteroids and additional immunosuppressants. More recently, autoantibody-depleting therapies such as rituximab, high-dose intravenous immunoglobulins, and immunoadsorption were shown to be valuable treatment options in PV.

Research Techniques Made Simple: Mass Spectrometry for Analysis of Proteins in Dermatological Research.

Identifying previously unknown proteins or detecting the presence of known proteins in research samples is critical to many experiments conducted in life sciences, including dermatology. Sensitive protein detection can help elucidate new intervention targets and mechanisms of disease, such as in autoimmune blistering skin diseases, atopic eczema, or other conditions. Historically, peptides from highly purified single proteins were sequenced, with many limitations, by stepwise degradation from the N-terminus to the C-terminus with subsequent identification by UV absorbance spectroscopy of the released amino acids (i.

Biochemical characterization of a novel antioxidant and angiotensin I-converting enzyme inhibitory peptide from Struthio camelus egg white protein hydrolysis.

A peptide from ostrich (Struthio camelus) egg white protein hydrolysate (OEWPH) was purified, characterized, and its antioxidant and enzyme inhibitory properties were evaluated. The OEWPH was prepared using pepsin and pancreatin, and then fractionated using reversed-phase high performance liquid chromatography. The antioxidant activity of the WG-9 peptide was investigated based on its scavenging capacity for 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, 2,20-azinobis (3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS), superoxide (O), hydroxyl (OH), and lipid peroxidation inhibition.

Gene cloning and characterization of a thermostable organic-tolerant α-amylase from Bacillus subtilis DR8806.

The gene encoding an extracellular α-amylase from Bacillus subtilis DR8806 was cloned into pET28a(+) vector and expressed in Escherichia coli BL21 (DE3). The recombinant enzyme with molecular mass of 76 kDa exhibited optimal activity at pH 5.0 and 70 °C with high stability in pH and temperature ranges of 4.

Expression and biochemical characterization of a thermophilic organic solvent-tolerant lipase from Bacillus sp. DR90.

The objective of the present study was the isolation, molecular cloning and biochemical characterization of a thermophilic organic solvent-resistant lipase from Bacillus sp. DR90. The lipase gene was expressed in Escherichia coli BL21(DE3) using pET-28a(+) vector.

Antioxidant properties of a human neuropeptide and its protective effect on free radical-induced DNA damage.

Human catestatin CgA352-372 (SL21) is an endogenous neuropeptide with multiple biological functions. The present study aimed to evaluate the antioxidant, antibacterial, cytotoxic, and DNA damage protective effects of SL21 neuropeptide. SL21 neuropeptide generated from the C-terminus of chromogranin A (CgA) was synthesized by solid-phase method.