Pro-Inflammatory Chemokines and Cytokines Dominate the Blister Fluid Molecular Signature in Patients with Epidermolysis Bullosa and Affect Leukocyte and Stem Cell Migration.

Hereditary epidermolysis bullosa (EB) is associated with skin blistering and the development of chronic nonhealing wounds. Although clinical studies have shown that cell-based therapies improve wound healing, the recruitment of therapeutic cells to blistering skin and to more advanced skin lesions remains a challenge. Here, we analyzed cytokines and chemokines in blister fluids of patients affected by dystrophic, junctional, and simplex EB. Our analysis revealed high levels of CXCR1, CXCR2, CCR2, and CCR4 ligands, particularly dominant in dystrophic and junctional EB. In vitro migration assays demonstrated the preferential recruitment of CCR4+ lymphocytes and CXCR1+, CXCR2+, and CCR2+ myeloid cells toward EB-derived blister fluids. Immunophenotyping of skin-infiltrating leukocytes confirmed substantial infiltration of EB-affected skin with resting (CD45RA+) and activated (CD45RO+) T cells and CXCR2+ CD11b+ cells, many of which were identified as CD16b+ neutrophils. Our studies also showed that abundance of CXCR2 ligand in blister fluids also creates a favorable milieu for the recruitment of the CXCR2+ stem cells, as validated by in vitro and in-matrix migration assays. Collectively, this study identified several chemotactic pathways that control the recruitment of leukocytes to the EB-associated skin lesions. These chemotactic axes could be explored for the refinement of the cutaneous homing of the therapeutic stem cells. © 2017 The Author

Cutaneous graft-versus-host disease after hematopoietic stem cell transplant - a review

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplants (allo-HSCT) associated with significant morbidity and mortality. The earliest and most common manifestation is cutaneous graft-versus-host disease. This review focuses on the pathophysiology, clinical features, prevention and treatment of cutaneous graft-versus-host disease. We discuss various insights into the disease’s mechanisms and the different treatments for acute and chronic skin graft-versus-host disease

Aberrant recruitment of leukocytes defines poor wound healing in patients with recessive dystrophic epidermolysis bullosa.

BACKGROUND: Poorly healing wounds are one of the major complications in patients suffering from recessive dystrophic epidermolysis bullosa (RDEB). At present, there are no effective means to analyze changes in cellular and molecular networks occurring during RDEB wound progression to predict wound outcome and design betted wound management approaches. OBJECTIVES: To better define mechanisms influencing RDEB wound progression by evaluating changes in molecular and cellular networks. METHODS: We developed a non-invasive approach for sampling and analysis of wound-associated constituents using wound-covering bandages. Cellular and molecular components from seventy-six samples collected from early, established and chronic RDEB wounds were evaluated by FACS-based immuno-phenotyping and ELISA. RESULTS: Our cross-sectional analysis determined that progression of RDEB wounds to chronic state is associated with the accumulation (up to 90 %) of CD16+CD66b+ mature neutrophils, loss of CD11b+CD68+ macrophages, and a significant increase (up to 50 %) in a number of CD11c+CD80+CD86+ activated professional antigen presenting cells (APC). It was also marked by changes in activated T cells populations including a reduction of CD45RO+ peripheral memory T cells from 80 % to 30 % and an increase (up to 70 %) in CD45RA+ effector T cells. Significantly higher levels of MMP9, VEGF-A and cathepsin G were also associated with advancing of wounds to poorly healing state. CONCLUSIONS: Our data demonstrated that wound-covering bandages are useful for a non-invasive sampling and analysis of wound-associated constituents and that transition to poorly healing wounds in RDEB patients as associated with distinct changes in leukocytic infiltrates, matrix-remodeling enzymes and pro-angiogenic factors at wound sites

Bullous Mastocytosis Mimicking Congenital Epidermolysis Bullosa

A 2-month-old female infant was referred to DebRA Mexico from the Regional Children's Hospital because of a generalized dermatosis from birth characterized by multiple blisters and erosions on the trunk, face and limbs, associated with minor trauma. A skin biopsy showing subepidermal blisters associated with a dermal infiltrate of Giemsa-positive cells and CD117-positive antibody was consistent with the diagnosis of bullous mastocytosis. Treatment with oral antihistamines, topical steroids, and antibiotics was initiated, leading to a remission of the lesions

Psoriatic arthritis, updated

Fil: Villarreal-Gonzalez, Antonio Jaime. Universidad Autónoma de Nuevo León. Hospital Universitario. Servicio de Reumatología; MéxicoFil: Flores-Alvarado, Diana Elsa. Universidad de Monterrey. Escuela de Medicina. Departamento de Ciencias Básicas; MéxicoFil: Salas-Alanis, Julio Cesar. Universidad de Monterrey. Escuela de Medicina. Departamento de Ciencias Básicas; MéxicoPsoriatic arthritis is a chronic systemic inflammatory disease with cutaneous and articular manifestation. Immunological and environmental factors are jointly involved in the development of this illness. Psoriatic arthritis forms part of the family of spondyloarthritis because up to 40% of cases are associated with the HLA-B27 a marker found in spondylitis. Clinically it is characterized by swelling, pain, tenderness and joint, ligament and tendon stiffness. The development in recent years of biological agents has caused a revolution in the pharmaceutical world and provided treatment for different autoimmune diseases. In this review, we discuss the pathogenesis, clinical manifestations, x-ray ultrasound findings, diseases scores and treatment

BRAF Mutation (V600E) Prevalence in Mexican Patients Diagnosed with Melanoma

Background: B-Raf is a serine/threonine protein kinase activating the MAP kinase/ERK-signaling pathway. It has been shown that 50% of melanomas harbor activating BRAF mutations, with over 90% being the V600E mutation. Objective: The goal of this research was to determine the prevalence of the BRAF V600E mutation in patients from Central Mexico diagnosed with primary melanoma. Methods: Skin biopsies from 47 patients with melanoma were obtained from the dermatology department of the Hospital General ‘Dr. Manuel Gea González' in Mexico City. For BRAF mutation determination, after DNA isolation, the gene region where the mutation occurs was amplified by PCR. Subsequently, the presence or absence of the V600E mutation was detected by Sanger sequencing performed at the private molecular diagnostic laboratory Vitagénesis in Monterrey, Mexico. Results: Of the 47 patients sampled, 6.4% harbored the V600E mutation. No statistical significance was found between mutations and the type of tumor