Dystrophic Epidermolysis Bullosa: COL7A1 Mutation Landscape in a Multi-Ethnic Cohort of 152 Extended Families with High Degree of Customary Consanguineous Marriages

Dystrophic epidermolysis bullosa is a heritable skin disease manifesting with sub-lamina densa blistering, erosions, and chronic ulcers. COL7A1, encoding type VII collagen, has been identified as the candidate gene for dystrophic epidermolysis bullosa. In this study, we have identified COL7A1 mutations in a large multi-ethnic cohort of 152 extended Iranian families with high degree of consanguinity. The patients were diagnosed by clinical manifestations, histopathology, and immunoepitope mapping. Mutation detection consisted of a combination of single nucleotide polymorphism-based whole-genome homozygosity mapping, Sanger sequencing, and gene-targeted next-generation sequencing. A total of 104 distinct mutations in COL7A1 were identified in 149 of 152 families (98%), 56 (53%) of them being previously unreported. Ninety percent of these mutations were homozygous recessive, reflecting consanguinity in these families. Three recurrent mutations were identified in five or more families, and haplotype analysis suggested a founder effect in two of them. In conclusion, COL7A1 harbored mutations in the overwhelming majority of patients with dystrophic epi-dermolysis bullosa, and most of them in this Iranian cohort were consistent with autosomal recessive inheri-tance. The mutation profile attests to the impact of consanguinity in these families

Metabolomic signature of amino acids in plasma of patients with non-segmental Vitiligo

Introduction Vitiligo pathogenesis is complicated, and several possibilities were suggested. However, it is well-known that the metabolism of pigments plays a significant role in the pathogenicity of the disease. Objectives We explored the role of amino acids in vitiligo using targeted metabolomics. Methods The amino acid profile was studied in plasma using liquid chromatography. First, 22 amino acids were derivatized and precisely determined. Next, the concentrations of the amino acids and the molar ratios were calculated in 31 patients and 34 healthy individuals. Results The differential concentrations of amino acids were analyzed and eight amino acids, i.e., cysteine, arginine, lysine, ornithine, proline, glutamic acid, histidine, and glycine were observed differentially. The ratios of cysteine, glutamic acid, and proline increased significantly in Vitiligo patients, whereas arginine, lysine, ornithine, glycine, and histidine decreased significantly compared to healthy individuals. Considering the percentage of skin area, we also showed that glutamic acid significantly has a higher amount in patients with less than 25% involvement compared to others. Finally, cysteine and lysine are considered promising candidates for diagnosing and developing the disorder with high accuracy (0.96). Conclusion The findings are consistent with the previously illustrated mechanism of Vitiligo, such as production deficiency in melanin and an increase in immune activity and oxidative stress. Furthermore, new evidence was provided by using amino acids profile toward the pathogenicity of the disorder.Peer reviewe

Elevated Serum Levels of Interleukin-15 in Pemphigus Vulgaris Patients: a Potential Therapeutic Target

Introduction: Pemphigus vulgaris (PV) is a rare autoimmune disease that causes painful blistering. Interleukin-15 (IL-15) as a member of the immunoregulatory cytokines family is associated with the development of the chronic inflammatory or autoimmune disease. There is not much information available in the literature on the exact role IL-15 plays in PV. Objectives: The goal of this study was to evaluate the serum levels of IL-15 in patients with PV and assess the association of IL-15 with anti-desmoglein antibodies and the severity of the disease. Methods: Fifty-three individuals affected with active PV and 38 age- and gender-matched healthy controls were participated in this study. Disease severity was assessed using Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). Serum levels of IL-15 (pg/mL) and anti-desmoglein antibodies (Dsg1, 3) were determined. Results: In the patient group, IL-15 serum levels were statistically higher than those in the control group (3.71 } 1.5 vs. 0.79 } 1.03, P \u3c 0.001). A positive correlation was found between serum levels of IL-15 and ABSIS (r = 0.5, P = 0.04). We found no significant correlation between serum concentrations of IL-15 and antidesmoglein antibodies (Dsg1 or Dsg3). Conclusions: An increase in serum level of IL-15 in patients with PV and its relationship with disease severity suggest that this cytokine possibly contributes to the pathogenesis of the disease and targeting IL-15 will likely provide a new insight into the treatment of this disease

Potential Molecular Mechanisms of Bisphenol A in Obesity Development

Bisphenol A (BPA), an endocrine disruptor, is associated with metabolic disorders. However, several studies have suggested that exposure to BPA can cause obesity. It has recently got more attention from scientists as a risk factor for obesity due to its ability to mimic natural estrogens and bind to their receptors. Nonetheless, the molecular mechanism underpinning the environmental etiology of metabolic disorders has not been not fully clarified. In this regard, BPA exposure directly disrupts endocrine regulation, neuroimmune and signaling pathways, and gut microbes, resulting in obesity. In addition, epidemiological studies have revealed a significant relationship between BPA exposure and the development of obesity, although conflicting results have been reported. Therefore, this review summarized the possible role and molecular mechanisms associated with BPA exposure that may lead to obesity based on in vivo and in vivo studies

Serum Leptin Levels in Pemphigus: A Case Control Study

Background. Pemphigus is an autoimmune blistering disease mediated by autoantibodies directed against keratinocyte adhesion molecules. Leptin, an adipocyte-derived hormone, plays a role in immune responses and promotes autoimmunity. Objectives. This study was conducted to determine whether serum leptin levels are altered in pemphigus patients and whether there is any correlation between leptin levels and the severity of disease. Methods. This study included 47 newly diagnosed patients with pemphigus and 43 age- and sex-matched healthy controls. Clinical characteristics and pemphigus area and activity score (PAAS) were assessed. Serum leptin levels (ng/mL) were measured by a commercial enzyme-linked immunosorbent assay (ELISA). Results. Patients did not differ significantly in serum leptin levels from healthy controls (median (range): 10.8 (0.1–110) ng/mL versus 12 (0.5–69.9) ng/mL and P=0.53). There was no significant association between serum leptin concentrations and severity of disease measured by PAAS (rs=0.06, P=0.70). Conclusion. The results suggest that pemphigus does not have a direct influence on serum leptin levels and the pathogenesis of pemphigus seems to be not dependent on the connection with adipose tissue

Multifocal epithelial hyperplasia: report of 3 cases

Multifocal epithelial hyperplasia (MEH) is a rare disorder characterized by multiple painless discrete and soft flattened papules on the oral mucosa. It is caused by human papilloma virus 13 and 32. The frequency of this disease varies widely from one geographic region to another. Generally it is very rare in Asia. Herein we report 3 Iranian cases with oral lesions, which showed clinical and histopathological characteristics of MEH disease. Two of them were siblings and HPV13 was detected in one of the patients

Multifocal epithelial hyperplasia: report of 3 cases

Multifocal epithelial hyperplasia (MEH) is a rare disorder characterized by multiple painless discrete and soft flattened papules on the oral mucosa. It is caused by human papilloma virus 13 and 32. The frequency of this disease varies widely from one geographic region to another. Generally it is very rare in Asia. Herein we report 3 Iranian cases with oral lesions, which showed clinical and histopathological characteristics of MEH disease. Two of them were siblings and HPV13 was detected in one of the patients

Autologous Fat Grafting in the Treatment of Facial Scleroderma

Systemic sclerosis (SSc) is a rare systemic autoimmune disease, characterized by progressive cutaneous and internal organ fibrosis. Orofacial manifestations of systemic sclerosis are extremely disabling and treatment options are limited. In this study, we aimed to assess the safety and efficacy of autologous fat grafting in the face of patients with systemic sclerosis. We enrolled 16 SSc patients suffering from facial sclerosis and limited mouth opening capacity. Autologous fat injection ranging from 15 to 40 ml was administered per patient, based on their face morphology. The patients were evaluated at baseline and 3 months after fat injection. Evaluations included mouth opening capacity, mouth handicap in systemic sclerosis (MHISS), Rodnan skin sclerosis score, skin biophysical properties using a sensitive biometrologic device with the assessment of cutaneous resonance running time (CRRT), volumizing and aesthetic effects based on pre- and posttreatment photographs, possible side effects, and global patient satisfaction. Clinical assessment showed autologous fat transfer significantly improved mouth opening capacity and the MHISS and Rodnan score of patients with facial scleroderma (p value <.001). The aesthetic and/or functional results of fat injection were satisfying to about 80% of the patients. The changes in CRRT values were not significant. Our findings support the possible therapeutic role of autologous fat grafting in improving facial scleroderma both in aesthetic and in functional aspects. This trial is registered with IRCT20180209038677N1