Pemphigus vulgaris (PV) is a potentially fatal blistering disease caused by autoantibodies against desmoglein 3 (Dsg3). Here, we clone anti-Dsg3 antibodies from four PV patients and identify pathogenic VH1-46 autoantibodies from all four patients. Unexpectedly, VH1-46 autoantibodies had relatively few replacement mutations. We reverted antibody somatic mutations to their germline sequences to determine the requirement of mutations for autoreactivity. Three of five VH1-46 germline-reverted antibodies maintain Dsg3 binding, compared to zero of five non-VH1-46 germline-reverted antibodies. Site-directed mutagenesis of VH1-46 antibodies demonstrate that acidic amino acid residues introduced by somatic mutation or heavy chain VDJ recombination are necessary and sufficient for Dsg3 binding. Our data suggest that VH1-46 autoantibody gene usage is commonly found in PV because VH1-46 antibodies require few to no mutations to acquire Dsg3 autoreactivity, which may favor their early selection. Common VH gene usage indicates common humoral immune responses, even among unrelated patients.

Clean beauty, also known as natural skin care, is having a moment. From 2017 to 2018, the natural skin care market grew by 23% to 1.6 billion dollars, accounting for over 25% of the 5.6 billion dollars of annual skin care sales in 2018. 1 Staunch warnings from influencers such as Gwyneth Paltrow, whose blog Goop warns readers "Do you want antifreeze (propylene glycol) in your moisturizer? We're going to guess no," 2 have ignited fear in consumers who are now hungry for skincare that is safe and nontoxic. However, the US Food and Drug Administration (FDA) has failed to define clean and natural, leaving these labels open to interpretation by nondermatologist retailers, bloggers, and celebrities who have set out to define clean beauty for themselves. While the clean beauty movement has demonized hundreds of compounds, in this Viewpoint, we argue that an arbitrary designation of clean or natural does not necessarily make products safer for consumers. Many of the ingredients that have been denounced by clean beauty evangelists seem to be selected haphazardly as companies attempt to "greenwash" their products to make them more attractive to conscientious shoppers. In July 2018, for example, Whole Foods released its updated list of unacceptable ingredients, which lists over 400 compounds they feel are unfit for their line of premium body care. 3 Their list of banned ingredients includes petrolatum, which dermatologists have consistently recommended to patients with skin barrier disruption owing to its nonallergenicity, superior qualities as a humectant, and economical cost that makes it accessible to patients of all backgrounds. The Campaign for Safe Cosmetics advocates for consumers to avoid a multitude of ingredients including parabens, 4 which the American Contact Dermatitis Society named 2019 nonallergen of the year. 5 Parabens are some of the least allergenic preservatives available, with rates of contact sensitization between 0.5% to 1.4%-rates that have been stable since the 1990s. 6 The Environmental Working Group's (EWG) safe skin database warns consumers against exposure to chemical sunscreen ingredients, 7 though a recent editorial in JAMA 8 explains that although there is evidence of systemic absorption of sunscreen ingredients, we do not yet have data to link this systemic absorption with toxic or adverse effects, and that sunscreens remain critical in our defense against keratinocytic skin cancers. Additionally, many so-called natural products contain high concentrations of botanical extracts that are a leading cause of both irritant and allergic contact dermatitis and photosensitization. 9 In a study done by the University of

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The study was approved by the institutional review board of the University of Pittsburgh Medical Center (IRB#0411029) and registered in clinicaltrials.gov (NCT00177268) as a tissue and blood banking protocol for CTCL patients for current and future CTCL research.

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