Genetic Associations and Differential mRNA Expression Levels of Host Genes Suggest a Viral Trigger for Endemic Pemphigus Foliaceus

The long search for the environmental trigger of the endemic pemphigus foliaceus (EPF, fogo selvagem) has not yet resulted in any tangible findings. Here, we searched for genetic asso ciations and the differential expression of host genes involved in early viral infections and innate antiviral defense. Genetic variants could alter the structure, expression sites, or levels of the gene products, impacting their functions. By analyzing 3063 variants of 166 candidate genes in 227 EPF patients and 194 controls, we found 12 variants within 11 genes associated with differential suscepti bility (p < 0.005) to EPF. The products of genes TRIM5, TPCN2, EIF4E, EIF4E3, NUP37, NUP50, NUP88, TPR, USP15, IRF8, and JAK1 are involved in different mechanisms of viral control, for example, the regulation of viral entry into the host cell or recognition of viral nucleic acids and proteins. Only two of nine variants were also associated in an independent German cohort of sporadic PF (75 patients, 150 controls), aligning with our hypothesis that antiviral host genes play a major role in EPF due to a specific virus–human interaction in the endemic region. Moreover, CCL5, P4HB, and APOBEC3G mRNA levels were increased (p < 0.001) in CD4+ T lymphocytes of EPF patients. Because there is limited or no evidence that these genes are involved in autoimmunity, their crucial role in antiviral responses and the associations that we observed support the hypothesis of a viral trigger for EPF, presumably a still unnoticed flavivirus. This work opens new frontiers in searching for the trigger of EPF, with the potential to advance translational research that aims for disease prevention and treatment

Charles C. Francis Papers, 1911-2013

An article, written by Elisabeth Bumiller for The New York Times, about President George W. Bush's decision to support a constitutional amendment banning same-sex marriage. The piece analyses what this move could mean for the campaign and includes Bush's history with LGBT issues and comments Charles C. Francis and others

Marked to Die-Cell Death Mechanisms for Keratinocyte Acantholysis in Pemphigus Diseases

Pemphigus is a group of blistering autoimmune diseases causing painful skin lesions, characterized by acantholysis and by the production of autoantibodies against, mainly, adhesion proteins. We reviewed the literature for molecules and/ or features involved in the 12 cell death pathways described by Nomenclature Committee on Cell Death, taking place in pemphigus patients, cell lines, or human skin organ cultures treated with sera or IgG from pemphigus patients or in pemphigus mouse models, and found 61 studies mentioning 97 molecules involved in cell death pathways. Among the molecules, most investigated were pleiotropic molecules such as TNF and CASP3, followed by FASL and CASP8, and then by FAS, BAX, BCL2, and TP53, all involved in more than one pathway but interpreted to function only within apoptosis. Most of these previous investigations focused only on apoptosis, but four recent studies, using TUNEL assays and/or electron microscopy, disqualified this pathway as a previous event of acantholysis. For PV, apoptolysis was suggested as a cell death mechanism based on pathogenic autoantibodies diversity, mitochondrial dysfunction, and p38 MAPK signaling. To answer those many questions that remain on cell death and pemphigus, we propose well-controlled, statistically relevant investigations on pemphigus and cell death pathways besides apoptosis, to overcome the challenges of understanding the etiopathology of pemphigus diseases