1034 Leukotriene B4 pathway and tissue damage markers are expressed by granulocytes in lesional skin in bullous pemphigoid C Margaroli 2 , B Bradley 1 , L Bhatt 3 , S Ahuja 3 , E Springman 3 , R Tirouvanziam 2 and RJ Feldman 1 1 Dermatology, Emory University School of Medicine, Atlanta, Georgia, United States, 2 Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States and 3 Celtaxsys, Inc, Atlanta, Georgia, United States Background: Bullous pemphigoid (BP) is an autoimmune blistering disease lacking an FDA- approved therapy that disproportionately affects elderly patients with pruritic blisters. Bi- opsies of BP patients show granulocyte infiltration of lesional skin. The leukotriene B4 (LTB4) pathway is a key positive feedback loop in granulocyte recruitment into tissues. Here, we sought to determine if LTB4 pathway and tissue damage markers were associated with granulocyte invasion in BP. Methods: Lesional skin was analyzed by immunohistochemistry (IHC, N¼4) for leukotriene A4 hydrolase (LTA4H), the rate-limiting enzyme in LTB4 synthesis, and the oxidizing enzyme myeloperoxidase. Matched blood and blister fluid were collected (N¼7) and analyzed by flow cytometry for leukocyte subsets and expression of LTA4H and BLT1 (LTB4 receptor). Results: Clinical characteristics of BP patients included mean age (72), BP disease area index activity (23.7) and pruritus score (20.9). IHC showed increased neutrophilic infiltrates with elevated LTA4H and myeloperoxidase levels in both skin and blister cavities. Flow cytometric analysis of blister fluid revealed the presence of neutrophils (median: 67.9% of total CD45+ leukocytes), monocytes / macrophages (median: 2.95%), and T cells (median: 2.37%), while eosinophils and B cells represented less than 0.05%. Neu- trophils and eosinophils significantly upregulated surface LTA4H and BLT1 in blister fluid compared to blood. Blister fluid neutrophils also upregulated release of the tissue-damaging proteases matrix metalloproteinase 9 and neutrophil elastase. Conclusion: Analysis of lesional skin from patients with BP identifies numerous neutrophils with upregulation of LTB4 pathway markers and release of tissue damaging enzymes. These findings suggest potential novel therapeutic targeting of BP via modulation of the LTB4 pathway. 1035 A systems biology analysis of endotypes in patients with psoriasis and psoriatic arthritis J Golden 2 , B Richardson 2 , A Young 1 , C Nichols 2 , R Xu 2 , NL Ward 1 , TS McCormick 1 , KD Cooper 1 and MJ Cameron 2 1 Dermatology, Case Western Reserve University, Cleveland, Ohio, United States and 2 Population & Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, United States With the hypothesis that new biomarker discovery will lead to better classification of in- dividuals with psoriasis and aid in targeting of their primary disease and associated comor- bidities, we are undertaking an endotype analysis of broadly-enrolled psoriasis and psoriatic arthritis (PsA) patients using a systems biology approach. Here we report our first findings using whole blood collected from psoriasis patients (n¼33 including 7 with PsA; mean PASI¼6.8 (range 0-29.6)) and 5 healthy controls. RNASeq was performed using Illumina TruSeq Total RNA kits and the NextSeq 550 sequencer (15M+ paired-end reads/sample, 75 cycles). Significant differentially expressed genes (DEGs; p<0.05 for all hits) were identified between psoriasis and PsA patients or their controls and pathway analysis was performed using gene set variation analysis. A general signature of psoriasis was found vs controls led by upregulated interferon signaling (e.g. MX1, ISG15) and inflammasome (e.g. LAMP2, NLRP2) genes that also tended to increase with age in linear regression analyses. Other endotypes were found using these proinflammatory biomarkers clustered by gender and ethnicity. Network analysis identified additional gene interactions with psoriasis in effector signaling, such as CD63, CALM2, and CASP1, as well as unique DEG in psoriasis patients with PSA, primarily in T/B cell and neutrophil activation. Cytometric analysis of the same samples revealed increased intermediate monocytes in psoriasis/PSA vs controls (p<0.01), confirming our prior results and the high inflammatory burden of psoriasis. Lastly, linear regression with PASI revealed a unique set of biomarkers involved in Treg (IL2RA) and B cell activity (CD72, CD19) in the most severe forms of psoriasis. Our ongoing strategy is to combine a multi-omic biomarker database with electronic health records to identify new therapeutic targets aimed at improving standard of care in psoriasis. 1036 Scalable production of CRISPR-corrected autologous iPSC derived skin grafts to treat epidermolysis bullosa JL Torkelson 1 , C Hansen 2 , J Jackow 2 , Z Guo 2 , H Hui-Zhen 1 , R Hayashi 3 , B Sallee 3 , K McCarthy 1 , G Neumayer 4 , PS McGrath 5 , G Bilousova 5 , I Kogut 5 , D Roop 5 , A Christiano 3 , M Wernig 4 and A Oro 1 1 Dermatology, Stanford, Stanford, California, United States, 2 Dermatology, Columbia University, New York, New York, United States, 3 Dermatology, Columbia University Medical Center, New York, New York, United States, 4 Pathology Stem Cell Institute, Stanford, Stanford, California, United States and 5 Dermatology, University of Colorado Denver, Denver, Colorado, United States Induced pluripotent stem cells (iPSCs) for autologous skin regeneration can treat genetic skin diseases such as recessive dystrophic epidermolysis bullosa (RDEB) which is characterized by type VII collagen (C7) deficiency. iPSCs have unlimited proliferative potential and have the potency to differentiate into different cell lineages. However, lacking is a reproducible and scalable platform to produce clinical grade iPSC-derived tissue stem cells. Here, we employ one-step reprogramming and gene-correction on primary fibroblasts to generate iPSCs fol- lowed by a novel defined differentiation method to produce functional keratinocyte (iKC) progenitors. While the differentiation process inherently yields a heterogenous population of progenitors and non-progenitors, we took advantage of the fact that normal human kerati- nocytes express high CD49F or ITGA6 and can be positively selected by FACS or magnetic bead enrichment (MACS) methods. MACS allows for large scale purifications and eliminates 96% of CD49f negative cells and enriches 18% of the CD49f bright cells. Post-enrichment, we have developed a method for an 18-fold expansion to generate enough keratinocyte grafts for clinical application. iKCs grafted onto immune-competent mice demonstrate C7 resto- ration and stratified epithelial markers. Preliminary safety studies investigated cellular bio- distribution using an Alu-PCR assay and showed undetectable levels of human cells in six major mouse organs. Altogether, we have developed a robust and scalable procedure to create graftable CRISPR-corrected autologous iKCs to treat RDEB patients. 1037 Transcriptome analysis in Se´zary syndrome and lymphocytic variant hypereosinophilic syndrome identify common and unique genes A Moerman-Herzog 1 , D Acheampong 1,2 , A Brooks 1 , S Blair 1 and HK Wong 1 1 Dermatology, University of Arkansas for Medical Science, Little Rock, Arkansas, United States and 2 Program in Bioinformatics, University of Arkansas at Little Rock, Little Rock, Arkansas, United States Sezary Syndrome (SS) and lymphocyte variant hypereosinophilic syndrome (L-HES) are mature T cell lymphoproliferations with similar manifestations of skin inflammation, pruritus, and eosinophilia. SS is a cutaneous lymphoma, while L-HES is a lymphoproliferation that can become malignant. Both show Th2 biased, and suggest developmental commonalities. Thus comparing their gene expression may shed light on genes important for Th2 manifestions and malignant transformation. Transcriptome profiles from Affymetrix U133 Plus 2 microarrays were compared: SS vs. normal CD4+CD45RO+ T cells (New), and L-HES CD3-CD4+ vs. normal CD3+CD4+ T cells (Public). Resting and activated gene expression were examined in both studies. SS T cells showed reductions in inducible cytokine genes compared to normal T cells and L-HES. Both SS and L-HES had common increased expression for ectopic, non- immune genes vs. normal T cells, and a subset of 158 genes differentially expressed in both SS and L-HES was detected (log2FC j1j, Rank Product FDR pfp  0.05). Concordantly expressed genes greatly outnumbered discordantly expressed genes. A number of previously described SS biomarker genes such as PLS3, STAT4, TWIST1 and others were dysregulated only in SS and confirmed in additional cohort of SS patients. TOX mRNA, a gene increased in SS, was elevated 2-fold following the clinical progression of L-HES patient 1 to T lymphoma, suggesting that this gene is important in lymphomagenesis. The genes increased specifically in SS highlighted in this study may be useful in classification and distinguishing these two similar clinical syndromes. Understanding the regulation of genes that are common and different in SS and L-HES may provide insight into the mechanisms involved in the common development of SS and L-HES and mechanism of lymphomagenesis. 1038 Convergent molecular and histologic profiles of guttate and plaque psoriasis JE Hawkes 1 , S Garcet 1 , X Zheng 1 , GG Krueger 2 , K Callis Duffin 2 and JG Krueger 1 1 Rock- efeller University, New York, New York, United States and 2 University of Utah, Salt Lake City, Utah, United States Guttate psoriasis is an eruptive form of psoriasis that occurs in young adults, is self-limiting, and frequently follows streptococcal pharyngitis. Approximately 1/3 of guttate patients develop chronic plaque psoriasis. To date, no studies have systematically characterized the molecular and histologic profiles of guttate psoriasis compared to plaque psoriasis. We prospectively collected lesional and non-lesional skin biopsies from guttate (n¼ 16) and plaque (n¼ 16) psoriasis patients for direct comparison of the microarray gene expression profile. Compared to plaque psoriasis, guttate psoriasis was associated with decreased epidermal acanthosis and T cell infiltration, as well as increased CD11c immunostaining. Gene expression analysis revealed 2080 DEGs in guttate versus 2008 in plaque psoriasis (FCH >2 FDR <0.05). 60% of DEGs were common to both variants. The expression pattern for genes that best characterize the core transcriptome of plaque psoriasis from multiple in- dependent studies (such as IL-17A, IL-17C, IL-17F, IL-23p19, IL-22, and IL-36) were highly similar between guttate and plaque samples and were validated by RT-PCR. Further pathway analysis revealed significant enrichment for Th17 Activation, IL-17A/IL-17F signaling, and Dendritic Cell Maturation in both variants. However, gene expression revealed significant differences in the guttate samples, including increased Th1/Th2 and IFNg signaling charac- terized by the higher levels of IL12p35, IL12RB2, STAT1, STAT3, SOC3, and IRF1. Guttate samples also had increased Treg cells and negative immune regulators compared to plaque psoriasis. Together, these findings suggest that higher Th1/Th2 signaling in guttate psoriasis patients along with increased regulatory T lymphocytes and negative immune regulators may be responsible for the self-limiting nature of this psoriasis variant. Ongoing studies will characterize differences in the T lymphocyte and immune cell populations, and genetic and environmental factors associated with guttate psoriasis. 1039 Novel mouse model of recessive dystrophic epidermolysis bullosa-squamous cell carcinoma J Jackow, C Hansen, R Hayashi, D Owens, R Perez-Lorenzo, D Delorenzo, Z Guo and A Christiano Dermatology, Columbia University, New York, New York, United States The high frequency and extremely aggressive behavior of squamous cell carcinoma from recessive dystrophic epidermolysis bullosa patients (RDEB-cSCC), as well as the lack of an appropriate preclinical mouse model recapitulating the RDEB-cSCC phenotype for testing effective therapies/drugs, creates an urgent need for generating such a model. Here, we established a novel mouse model for RDEB-cSCC, in which we generated 3D cSCC skin constructs (SCs) using RDEB-cSCC and RDEB fibroblasts (FB), which were then grafted onto immunocompromised mice. 16 out of 18 animals that were grafted with RDEB patient- derived cSCC and FB developed tumors within 4 weeks post-grafting, with characteristic morphological features of human RDEB-cSCC. H&E staining of RDEB-cSCC grafts revealed invading epithelial cell columns and differentiated tumor cell islands in the upper dermis. Immunofluorescence (IF) staining showed a complete lack of C7 and increased pSTAT3 expression in the RDEB-cSCC grafted skin construct. Keratin 14, keratin 10 and E-cadherin IF staining were increased within the RDEB-cSCC grafted tumor tissue, indicating the epithelial origin of RDEB-cSCC cells in the dermis and their differentiation. Further, the RDEB-cSCC grafted tumor displayed high proliferation as demonstrated by increased Ki-67 + and p63 + expression seen in IF staining and reduced expression in vimentin staining compared with normal grafts. Moreover, serial transplantation revealed that 88% of RDEB-cSCC tumors had similar biology to the primary tumor (developed on the initial immunocompetent mouse) within 2 weeks post-transplantation onto a second immunocompetent mouse. Our data established a new preclinical model RDEB-cSCC, and an important new method for drug testing in translational cancer research. Translational Studies | ABSTRACTS www.jidonline.org S179