Beyond the skin: B cells in pemphigus vulgaris, tolerance and treatment.

Pemphigus vulgaris (PV) is a rare autoimmune bullous disease characterized by blistering of the skin and mucosa owing to the presence of autoantibodies against the desmosome proteins desmoglein 3 and occasionally in conjunction with desmoglein 1. Fundamental research into the pathogenesis of PV has revolutionized its treatment and outcome with rituximab, a B-cell-depleting therapy. The critical contribution of B cells to the pathogenesis of pemphigus is well accepted.

Paraneoplastic pemphigus: A detailed case series from the Netherlands revealing atypical cases.

Background: Paraneoplastic pemphigus (PNP) is an extremely rare life-threatening blistering autoimmune disease that is associated with an underlying neoplasm. There is a set diagnostic criterion for PNP, which is primarily based on a severe stomatitis and the detection of specific antibodies against envoplakin, periplakin and alpha-2-macroglobulin-like protein 1. However, it has become increasingly evident that there are patients with PNP that do not meet all the diagnostic criteria requirements.

Functional investigation of two simultaneous or separately segregating DSP variants within a single family supports the theory of a dose-dependent disease severity.

Desmoplakin (DP) is an important component of desmosomes, essential in cell-cell connecting structures in stress-bearing tissues. Over the years, many hundreds of pathogenic variants in DSP have been associated with different cutaneous and cardiac phenotypes or a combination, known as a cardiocutaneous syndrome. Of less than 5% of the reported DSP variants, the effect on the protein has been investigated.

Comparison of Two Diagnostic Assays for Anti-Laminin 332 Mucous Membrane Pemphigoid.

Anti-laminin 332 mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by predominant mucosal lesions and autoantibodies against laminin 332. The exact diagnosis of anti-laminin 332 MMP is important since nearly 30% of patients develop solid cancers. This study compared two independently developed diagnostic indirect immunofluorescence (IF) tests based on recombinant laminin 332 expressed in HEK239 cells (biochip mosaic assay) and the migration trails of cultured keratinocytes rich in laminin 332 (footprint assay).

Insights into clinical and diagnostic findings as well as treatment responses in patients with mucous membrane pemphigoid: A retrospective cohort study.

Background: The variable clinical severity of mucous membrane pemphigoid (MMP) often leads to diagnostic and therapeutic delays.

Objective: To describe the characteristics of a large cohort of patients with MMP.

Methods: A retrospective review of clinical and diagnostic characteristics as well as treatment responses in 145 patients with MMP.

Direct Evidence of Endothelial Dysfunction and Glycocalyx Loss in Dermal Biopsies of Patients With Chronic Kidney Disease and Their Association With Markers of Volume Overload.

Cardiovascular morbidity is a major problem in patients with chronic kidney disease (CKD) and endothelial dysfunction (ED) is involved in its development. The luminal side of the vascular endothelium is covered by a protective endothelial glycocalyx (eGC) and indirect evidence indicates eGC loss in CKD patients. We aimed to investigate potential eGC loss and ED in skin biopsies of CKD patients and their association with inflammation and volume overload.

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.

Paraneoplastic pemphigus associated with post-transplant lymphoproliferative disorder after small bowel transplantation.

Background: PNP is a malignancy-associated autoimmune mucocutaneous syndrome due to autoantibodies against plakins, desmogleins, and other components of the epidermis and basement membrane of epithelial tissues. PNP-causing malignancies comprise mainly lymphoproliferative and hematologic neoplasms. PNP is extremely rare, especially in children.

Assessment of Diagnostic Strategy for Mucous Membrane Pemphigoid.

Importance: An accurate diagnosis of mucous membrane pemphigoid (MMP) is essential to reduce diagnostic and therapeutic delay.

Objective: To assess the diagnostic accuracy of direct immunofluorescence microscopy on mucosal biopsy specimens and immunoserology in a large cohort of patients with suspected MMP.

Design, Setting, And Participants: This retrospective cohort study was carried out in a single tertiary care center for blistering diseases between January 2002 and March 2019.

The expression pattern of N-acetyltransferase 1 in healthy human skin.

Background: N-acetyltransferase 1 (NAT1) is an enzyme expressed among others in keratinocytes in human skin. NAT1 is important in the biotransformation of aromatic amines, an important example being p-phenylenediamine (PPD), a hair dye molecule. Unoxidized PPD penetrates the skin and is N-acetylated by NAT1.

Is skin autofluorescence (SAF) representative of dermal advanced glycation endproducts (AGEs) in dark skin? A pilot study.

Aims: Non-invasively assessed skin autofluorescence (SAF) measures advanced glycation endproducts (AGEs) in the dermis. SAF correlates with dermal AGEs in Caucasians and Asians, but studies in dark-skinned subjects are lacking. In this pilot we aimed to assess whether SAF signal is representative of intrinsic fluorescence (IF) and AGE accumulation in dark skin.

Autoantibody Detection for Diagnosis in Direct Immunofluorescence-Negative Mucous Membrane Pemphigoid: Ocular and Other Sites Compared.

Purpose: To assess whether a panel of serum pemphigoid autoantibody tests could be used to confirm an immunopathologic diagnosis of mucous membrane pemphigoid (MMP) in direct immunofluorescent negative (DIF-) MMP patients.

Design: Prospective cross-sectional study.

Participants: Seventy-six patients with multisite MMP with 45 matched control participants.

Non-bullous Lichen Planus Pemphigoides: A Case Report.

is missing (Short communication).

Hyperkeratotic hand eczema: Eczema or not?

Background: Hyperkeratotic hand eczema (HHE) is a typical clinical hand eczema subtype with a largely unknown pathophysiology.

Objective: To investigate histopathology, expression of keratins (K), epidermal barrier proteins, and adhesion molecules in HHE.

Methods: Palmar skin biopsies (lesional and perilesional) were obtained from seven HHE patients and two healthy controls.

Endocytosis of IgG, Desmoglein 1, and Plakoglobin in Pemphigus Foliaceus Patient Skin.

Pemphigus foliaceus (PF) is one of the two main forms of pemphigus and is characterized by circulating IgG to the desmosomal cadherin desmoglein 1 (DSG1) and by subcorneal blistering of the skin. The pathomechanism of blister formation in PF is unknown. Previously we have shown that PF IgG induces aggregation of DSG1, plakoglobin (PG), and IgG outside of desmosomes, what in immunofluorescence of PF patient skin visualizes as a granular IgG deposition pattern with a limited number of coarse IgG aggregates between cells.