Based on our previous findings, we aimed to elucidate whether PV acantholysis in a mouse model may be mediated by activation of a disintegrin and metalloproteinase 10 (ADAM10).
Moreover, AuAb absorption on recombinant Dsc3, M3AR, or SPCA1 both prevented skin blistering in the passive transfer of AuAbs model of PV in BALB/c mice and significantly decreased the extent of acantholysis in a neonatal mouse skin explant model.
The gold standard for the diagnosis of pemphigus vulgaris is the detection of autoantibodies or complement component 3 by direct immunofluorescence microscopy of a perilesional biopsy.
This study supports the hypothesis that complement C3 is important in PV acantholysis and that complement activation is increased by IL-1alpha and TNF-alpha.
To investigate the contribution of M2 macrophages to the pathogenesis of bullous pemphigoid (BP) and pemphigus vulgaris (PV), we employed immunohistochemical staining for CD163 and CD206, as well as pSTAT1, pSTAT6, interleukin (IL)-4, IL-13, CCL17, CCL18 and Foxp3 in the lesional skin of 10 cases of BP and PV.
To investigate the contribution of M2 macrophages to the pathogenesis of bullous pemphigoid (BP) and pemphigus vulgaris (PV), we employed immunohistochemical staining for CD163 and CD206, as well as pSTAT1, pSTAT6, interleukin (IL)-4, IL-13, CCL17, CCL18 and Foxp3 in the lesional skin of 10 cases of BP and PV.
Additionally, our microarray assay showed that the level of chemokine CCL19 was significantly elevated, suggesting active T-/B-lymphocyte trafficking and aggregation in the pemphigus vulgaris lesions.
Induction of T regulatory cells by the superagonistic anti-CD28 antibody D665 leads to decreased pathogenic IgG autoantibodies against desmoglein 3 in a HLA-transgenic mouse model of pemphigus vulgaris.
Among the large number of studied SNPs, it was found that several SNPs in different genes might control the susceptibility of PV, including TNFA (rs361525, rs1800629, rs1800629), IL10 (rs1800871, rs1800896, rs1800871, and rs1800872), IL6 (rs1800795), CTLA4 (rs231775), ICOS (rs10932029), CD86 (rs1129055), DSG3 (rs8085532, rs3911655, rs3848485, rs3794925, rs1466379), ST18 (rs2304365, rs17315309) and TAP2 (rs7454108), probably in a population-specific manner.
Inhibition of caspases by z-VAD-fmk as well as overexpression of Fas-associated death domain-like interleukin-1beta-converting enzyme (FLICE)-like inhibitory proteins FLIP(L) and FLIP(S) to inhibit receptor-mediated apoptosis did not block PV-IgG-induced effects, indicating that apoptosis was not required.
In comparison to healthy controls, the following observations were made: (i) Hsp90 was highly expressed in the skin of BP patients, whereas its serum levels were decreased and inversely associated with IgG autoantibody levels against the NC16A immunodominant region of the BP180 autoantigen, (ii) in contrast, neither aberrant levels of circulating Hsp90 nor any correlation of this protein with serum autoantibodies was found in a control cohort of autoimmune bullous disease patients with pemphigus vulgaris, (iii) Hsp90 was highly expressed in and restrictedly released from peripheral blood mononuclear cells of BP patients, and (iv) Hsp90 was potently induced in and restrictedly secreted from human keratinocyte (HaCaT) cells by BP serum and isolated anti-BP180 NC16A IgG autoantibodies, respectively.
Specific Human Leukocyte Antigen Class II (HLA II) molecules associated with pemphigus vulgaris (PV), mucous membraine pemphigoid (MMP), and mixed connective tissue disease (MCTD) may react with multiple T cell epitopes within desmoglein 3 (Dsg 3), bullous pemphigoid antigen 2 (BPAG 2), and 70 kDa polypeptide small nuclear ribonucleoproteins (snRNP70) in autoantibody production.
Analysis of the frequency of genotypes and alleles of +49A/GCTLA4 gene polymorphism showed no statistically significant differences between the PV and PF patients and the controls.