Mucous membrane pemphigoid or cicatricial pemphigoid is a mucocutaneous blistering disease characterized by autoantibodies to different molecules in the basement membrane zone. Our objectives were to identify the target antigen recognized by sera from 20 untreated patients with pemphigoid disease limited to the oral cavity, and to determine the pathogenicity of autoantibodies in oral pemphigoid, with an organ culture model. We conducted indirect immunofluorescence, immunoblot, and immunoprecipitation assays, with accompanying absorption experiments, using normal human skin, conjunctiva and gingiva, bovine gingiva and a tumor cell line, which were reacted with sera from patients with oral pemphigoid, anti-alpha6 antibody, and control sera. Sera of oral pemphigoid patients selectively and specifically bound to human alpha6 integrin, a 120-kDa protein present in gingiva and the tumor cell line. Oral pemphigoid sera and anti-alpha6 antibody produced separation of epithelium from basement membrane (blister formation) of normal human buccal mucosa, after 48 hours, in organ culture.

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Arf GTPase-activating proteins (Arf GAPs) control the activity of ADP-ribosylation factors (Arfs) by inducing GTP hydrolysis and participate in a diverse array of cellular functions both through mechanisms that are dependent on and independent of their Arf GAP activity. A number of these functions hinge on the remodeling of actin filaments. Accordingly, some of the effects exerted by Arf GAPs involve proteins known to engage in regulation of the actin dynamics and architecture, such as Rho family proteins and nonmuscle myosin 2. Circular dorsal ruffles (CDRs), podosomes, invadopodia, lamellipodia, stress fibers and focal adhesions are among the actin-based structures regulated by Arf GAPs. Arf GAPs are thus important actors in broad functions like adhesion and motility, as well as the specialized functions of bone resorption, neurite outgrowth, and pathogen internalization by immune cells. Arf GAPs, with their multiple protein-protein interactions, membrane-binding domains and sites for post-translational modification, are good candidates for linking the changes in actin to the membrane. The findings discussed depict a family of proteins with a critical role in regulating actin dynamics to enable proper cell function.

BackgroundSystemic lupus erythematosus (SLE or lupus) is an autoimmune multisystem disease. While a complete understanding of lupus’ origins, mechanisms, and progression is not yet available, a number of studies have demonstrated correlations between disease prevalence and severity, gender, and race. There have been few population based studies in the United StatesObjectivesTo assess temporal changes in demographics and hospital mortality of patients with lupus in Washington State from 2003 to 2011Study DesignThis study used data from the Healthcare Cost and Utilization Project (HCUP), a patient information database, and data from the Washington State census to study a group of patients in the state. Lupus hospitalizations were defined as any hospitalization with an ICD-9-CM diagnosis code for systemic lupus erythematosus. Regression analysis was used to assess the effect of calendar time on demographics and hospital outcomes.ResultsThere were a total of 18,905 patients in this study with a diagnostic code for lupus. The mean age of the group was 51.5 years (95% CI: 50.6-52.3) in 2003 and 51.3 years (95% CI: 50.6-52.0) in 2011. The population was 88.6% female. Blacks were 2.8 times more likely to have a lupus hospitalization than whites when compared to the Washington population. While hospital mortality decreased during this eight year period (3.12% in 2003 to 1.28% in 2011, p=0.001) hospital length of stay remained statistically unchanged at an average of 4.9 days during that eight year period. We found a significant decrease in annual hospital mortality over the study period [odds ratio(OR): 0.92 per year, 95% CI 0.88-0.96, P<0.001]. Hospital mortality was higher in males (2.6% male death to 1.8% female death)ConclusionsIn this large group of hospitalized lupus patients in Washington, hospital length of stay remained relatively stable over time but hospital mortality decreased by over 50% over the eight year study period.