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Surgical resection with negative margins remains the standard of care for high-risk cutaneous squamous cell carcinoma (SCC). However, surgical management is often limited by poor intraoperative tumor visualization and inability to detect occult nodal metastasis. The inability to intraoperatively detect microscopic disease can lead to additional surgery, tumor recurrence, and decreased survival.A comprehensive literature review was conducted to identify studies incorporating optical imaging technology in the management of cutaneous SCC (January 1, 2000-December 1, 2014).Several innovative optical imaging techniques, Raman spectroscopy, confocal microscopy, and fluorescence imaging, have been developed for intraoperative surgical guidance. Fifty-seven studies review the ability of these techniques to improve cutaneous SCC localization at the gross and microscopic level.Significant advances have been achieved with real-time optical imaging strategies for intraoperative cutaneous SCC margin assessment and tumor detection. Optical imaging holds promise in improving the percentage of negative surgical margins and in the early detection of micrometastatic disease. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2204-E2213, 2016.

To gain global pathway perspective of ex vivo viral infection models using human peripheral blood mononuclear cells (PBMCs), we conducted expression analysis on PBMCs of healthy donors. RNA samples were collected at 3 and 24 h after PBMCs were challenged with the Toll-like receptor-3 (TLR3) agonist polyinosinic acid-polycytidylic acid [poly(I:C)] and analyzed by internally developed cDNA microarrays and TaqMan PCR. Our results demonstrate that poly(I:C) challenge can elicit certain gene expression changes, similar to acute viral infection. Hierarchical clustering revealed distinct immediate early, early-to-late, and late gene regulation patterns. The early responses were innate immune responses that involve TLR3, the NF-κB-dependent pathway, and the IFN-stimulated pathway, whereas the late responses were mostly cell-mediated immune response that involve activation of cell adhesion, cell mobility, and phagocytosis. Overall, our results expanded the utilities of this ex vivo model, which could be used to screen molecules that can modulate viral stress-induced inflammation, in particular those mediated via TLRs.

KLF4 is induced upon growth-arrest in vitro and during epithelial maturation in vivo, and is essential for proper cell fate specification of post-mitotic cells. In spite of a normal role in post-mitotic cells, expression is upregulated and constitutive in certain tumor types. KLF4 functions as an oncogene in vitro, and enforced expression in basal cells of mouse skin rapidly induces lesions similar to hyperplasia, dysplasia and squamous cell carcinoma (SCC). Here we used conditional expression to characterize early steps in KLF4-mediated tumor initiation. In contrast to SCC-like lesions that result when using a conditional, keratin 14 promoter-dependent strategy, lower conditional expression achieved using a MMTV promoter induced only epidermal cycling within morphologically normal skin, a process we termed occult cell turnover. Surprisingly, KLF4-induced hyperplastic lesions showed increased transgene-derived mRNA and protein in maturing, PCNA-negative cells, a property of endogenous KLF4. In contrast, hyperplastic lesions induced by GLI1, a control, showed uniform transgene expression. In KLF4-induced dysplasia and SCC the complementarity of KLF4 and PCNA was replaced by concordance of the two proteins. These studies show that KLF4 transcripts are normally suppressed in cycling cells in a promoter-independent fashion, consistent with a post-transcriptional control, and reveal loss of this control in the transition from hyperplasia to dysplasia. Like the mouse tumors, human cutaneous SCCs and adjacent dysplasias frequently showed maturation-independence of KLF4, with co-expression of KLF4 and PCNA. A smaller subset of human SCCs showed complementarity of KLF4 and PCNA, similar to hyperplastic mouse skin. The results identify parallels between a mouse model and human primary tumors, and show that successive increases of KLF4 in the nuclei of basal keratinocytes leads to occult cell turnover followed by hyperplasia, dysplasia, and invasive SCC.

Background A significant portion of cutaneous melanoma may remain after subtotal incisional biopsy. The accuracy of microstaging and impact on clinical practice in this scenario are unknown. Objective Our purpose was to examine microstaging accuracy of an initial incisional biopsy with a significant portion of the clinical lesion remaining (≥50%). Methods Patients with cutaneous melanoma, diagnosed by incisional biopsy with ≥50% of the lesion remaining, were prospectively evaluated for microstaging accuracy, comparing initial Breslow depth (BD1) to final depth (BD2) after excision of the residual lesion. Impact on prognosis and treatment was also evaluated. Results Two hundred fifty of 1783 patients (14%) presented with ≥50% residual clinical lesion after incisional biopsy. The mean BD1 was 0.66 mm; the mean BD2, 1.07 mm ( P =.001). After complete excision of the residual lesion, upstaging occurred in 21% and 10% became candidates for sentinel node biopsy. Conclusion An incisional biopsy with ≥50% clinical lesion remaining afterward may be inadequate for accurate microstaging of melanoma. This scenario is relatively uncommon but clinically significant.

In excising basal and squamous cell carcinomata, the surgical margin that is wide enough to completely remove the tumor an acceptable percentage of the time and narrow enough to minimize removal of excessive normal tissue must be selected. This task can be reliably accomplished with comprehensive knowledge of factors that affect subclinical tumor extension such as tumor appearance, diameter, histology, location, treatment status, and, in the case of squamous cell carcinoma, vertical invasion depth and involvement of subcutaneous fat. Information regarding these factors along with specific recommendations about excisional margins for basal cell and squamous cell carcinomata is presented.

Although patients with neurofibromatosis (NF) have an increased incidence of tumors, there is only one study that suggests that NF1 patients may have an increased risk for epithelial malignancies. We present a patient with known NF1 who had developed multiple epithelial tumors since early in his life. All but one of these tumors were morphologically most consistent with trichoepitheliomas. Loss of heterozygosity (LOH) for Patched 1 gene (PTCH) was demonstrated within two of the trichoepitheloma-like tumors and one tumor diagnosed as basal cell carcinoma, and the patient was show to have a PTCH gene deletion. To our knowledge, a patient presenting with both NF1 and multiple trichoepitheliomas (MTE) has not previously been reported. The dysregulation in cellular proliferation and signaling induced by decreased NF1 along with the PTCH gene mutation may explain the pattern of immunohistochemical staining within these tumors, and the rare association of NF1 with epithelial neoplasms.

Importance Skin cancer is the most common malignancy occurring after organ transplantation. Although previous research has reported an increased risk of skin cancer in solid organ transplant recipients (OTRs), no study has estimated the posttransplant population–based incidence in the United States. Objective To determine the incidence and evaluate the risk factors for posttransplant skin cancer, including squamous cell carcinoma (SCC), melanoma (MM), and Merkel cell carcinoma (MCC) in a cohort of US OTRs receiving a primary organ transplant in 2003 or 2008. Design, Setting, and Participants This multicenter retrospective cohort study examined 10 649 adult recipients of a primary transplant performed at 26 centers across the United States in the Transplant Skin Cancer Network during 1 of 2 calendar years (either 2003 or 2008) identified through the Organ Procurement and Transplantation Network (OPTN) database. Recipients of all organs except intestine were included, and the follow-up periods were 5 and 10 years. Main Outcomes and Measures Incident skin cancer was determined through detailed medical record review. Data on predictors were obtained from the OPTN database. The incidence rates for posttransplant skin cancer overall and for SCC, MM, and MCC were calculated per 100 000 person-years. Potential risk factors for posttransplant skin cancer were tested using multivariate Cox regression analysis to yield adjusted hazard ratios (HR). Results Overall, 10 649 organ transplant recipients (mean [SD] age, 51 [12] years; 3873 women [36%] and 6776 men [64%]) contributed 59 923 years of follow-up. The incidence rates for posttransplant skin cancer was 1437 per 100 000 person-years. Specific subtype rates for SCC, MM, and MCC were 812, 75, and 2 per 100 000 person-years, respectively. Statistically significant risk factors for posttransplant skin cancer included pretransplant skin cancer (HR, 4.69; 95% CI, 3.26-6.73), male sex (HR, 1.56; 95% CI, 1.34-1.81), white race (HR, 9.04; 95% CI, 6.20-13.18), age at transplant 50 years or older (HR, 2.77; 95% CI, 2.20-3.48), and being transplanted in 2008 vs 2003 (HR, 1.53; 95% CI, 1.22-1.94). Conclusions and Relevance Posttransplant skin cancer is common, with elevated risk imparted by increased age, white race, male sex, and thoracic organ transplantation. A temporal cohort effect was present. Understanding the risk factors and trends in posttransplant skin cancer is fundamental to targeted screening and prevention in this population.

Motivation Next-generation sequencing (NGS) technologies have become much more efficient, allowing whole human genomes to be sequenced faster and cheaper than ever before. However, processing the raw sequence reads associated with NGS technologies requires care and sophistication in order to draw compelling inferences about phenotypic consequences of variation in human genomes. It has been shown that different approaches to variant calling from NGS data can lead to different conclusions. Ensuring appropriate accuracy and quality in variant calling can come at a computational cost. Results We describe our experience implementing and evaluating a group-based approach to calling variants on large numbers of whole human genomes. We explore the influence of many factors that may impact the accuracy and efficiency of group-based variant calling, including group size, the biogeographical backgrounds of the individuals who have been sequenced, and the computing environment used. We make efficient use of the Gordon supercomputer cluster at the San Diego Supercomputer Center by incorporating job-packing and parallelization considerations into our workflow while calling variants on 437 whole human genomes generated as part of large association study. Conclusions We ultimately find that our workflow resulted in high-quality variant calls in a computationally efficient manner. We argue that studies like ours should motivate further investigations combining hardware-oriented advances in computing systems with algorithmic developments to tackle emerging ‘big data’ problems in biomedical research brought on by the expansion of NGS technologies. Electronic supplementary material The online version of this article (doi:10.1186/s12859-015-0736-4) contains supplementary material, which is available to authorized users.

Recent advances in genetics have spurred rapid progress towards the systematic identification of genes involved in complex diseases. Still, the detailed understanding of the molecular and physiological mechanisms through which these genes affect disease phenotypes remains a major challenge. Here, we identify the asthma disease module, i.e. the local neighborhood of the interactome whose perturbation is associated with asthma, and validate it for functional and pathophysiological relevance, using both computational and experimental approaches. We find that the asthma disease module is enriched with modest GWAS P-values against the background of random variation, and with differentially expressed genes from normal and asthmatic fibroblast cells treated with an asthma-specific drug. The asthma module also contains immune response mechanisms that are shared with other immune-related disease modules. Further, using diverse omics (genomics, gene-expression, drug response) data, we identify the GAB1 signaling pathway as an important novel modulator in asthma. The wiring diagram of the uncovered asthma module suggests a relatively close link between GAB1 and glucocorticoids (GCs), which we experimentally validate, observing an increase in the level of GAB1 after GC treatment in BEAS-2B bronchial epithelial cells. The siRNA knockdown of GAB1 in the BEAS-2B cell line resulted in a decrease in the NFkB level, suggesting a novel regulatory path of the pro-inflammatory factor NFkB by GAB1 in asthma.

Ablative fractionated resurfacing has gained significant traction as an effective treatment for acne, burn, traumatic, and surgical scars over recent years. We report a case of a severely depressed, atrophic scar on the cheek of a middle aged woman treated with a 10,600 nm factionated CO2 laser. Serial treatments were performed, resulting in marked improvement in scar contour, texture, and overall cosmesis. Our report highlights the utility of ablative fractionated resurfacing for the treatment of post-traumatic, atrophic scars on the face.

Protegrin antimicrobial peptides possess activity against gram-positive and gram-negative bacteria and yeasts. An extensive structure-activity relationship (SAR) study was conducted on several hundred protegrin analogues to gain understanding of the relationship between the primary and secondary structure of the protegrins and their antimicrobial activities, and to identify a protegrin analogue for clinical development. Native sequence protegrins are cationic, amphiphilic peptides that are characterized by the presence of a beta-sheet structure that is maintained by two disulfide bridges. The presence of the beta-sheet is key to the stability of the protegrin structure; linearized analogues or analogues that have amino acid substitutions that eliminate hydrogen bonding across the beta-sheet have reduced activity, especially in the presence of physiological concentrations of NaCl. Also, maintaining amphiphilicity of the beta-sheet is key; analogues with substitutions of polar amino acids in the hydrophobic face have reduced activity. Analogues with reduced positive charge tend to be less active, an observation that is more marked for gram-negative than gram-positive bacteria, and may implicate binding to lipopolysaccharide as a key mechanistic step in the killing of gram-negative bacteria. A very large number of amino acid substitutions are tolerated by the protegrin structure, implying that overall structural features such as amphiphilicity, charge, and shape are more important to activity than the presence of specific amino acids. This lack of importance of specific stereochemistry is supported by the fact that completely D-amino acid substituted protegrins are fully potent. Based on the SAR studies, and on the microbiological data from an animal model, one protegrin analogue, IB-367, was selected for clinical development as a topical agent to prevent the oral mucositis associated with cancer therapy.

Dermatologists commonly encounter lesions arising on the lips that require excision either for biopsy or treatment. These conditions can be benign, premalignant, or malignant. Examples of these conditions include hemangiomas, arteriovenous malformations, venous lakes, cheilitis glandularis, cheilitis granulomatosa, actinic cheilitis, Bowen's disease, lentigo maligna, malignant melanoma in situ, basal cell carcinoma, squamous cell carcinoma, and malignant melanoma, among others. This article will review several surgical techniques used for excision and repair of the lip in the treatment of these conditions. Our intent is to provide specific suggestions, without being dogmatic, in a spirit of practicality. Topics covered will include the importance of the lip, lip anatomy as it pertains to cutaneous surgery, techniques for obtaining lip anesthesia, partial-thickness lip excision, full-thickness lip excision, surgical vermilionectomy, and carbon dioxide laser vermilionectomy. Emphasis will be placed on those surgical techniques that involve excision and repair of conditions commonly encountered in a general dermatology practice. Extensive reconstructive procedures, reconstruction of Mohs micrographic surgical defects, and lip augmentation are beyond the scope of this article.

Intraoperative, real-time fluorescence imaging may significantly improve tumor visualization and resection and postoperatively, in pathological assessment. To this end, we sought to determine the optimal FDA approved therapeutic monoclonal antibody for optical imaging of human cutaneous squamous cell carcinoma (cSCC). A near-infrared (NIR) fluorescent probe (IRDye800) was covalently linked to bevacizumab, panitumumab or tocilizumab and injected systemically into immunodeficient mice bearing either cutaneous tumor cell lines (SCC13) or cutaneous human tumor explants. Tumors were then imaged and resected under fluorescent guidance with the SPY, an FDA-approved intraoperative imaging system, and the Pearl Impulse small animal imaging system. All fluorescently labeled antibodies delineated normal tissue from tumor in SCC13 xenografts based on tumor-to-background (TBR) ratios. The conjugated antibodies produced TBRs of 1.2-2 using SPY and 1.6-3.6 using Pearl; in comparison, isotype control antibody IgG-IRDye produced TBRs of 1.0 (SPY) and 0.98 (Pearl). Comparison between antibodies revealed them to be roughly equivalent for imaging purposes with both the SPY and Pearl (p = 0.89 SPY, p = 0.99 Pearl; one way ANOVA). Human tumor explants were also imaged and tumor detection was highest with panitumumab-IRDye800 when using the SPY (TBR 3.0) and Pearl (TBR 4.0). These data suggest that FDA approved antibodies may be clinically used for intraoperative detection of cSCC.

Infliximab has been shown to induce clinical response and remission in ulcerative colitis (UC). To characterize the biological response of patients to infliximab, we analyzed the mRNA expression patterns of mucosal colonic biopsies taken from UC patients enrolled in the Active Ulcerative Colitis Trial 1 (ACT1) study.Biopsies were obtained from 48 UC patients before treatment with 5 or 10 mg/kg infliximab, and at 8 and 30 weeks after treatment (n = 113 biopsies). Global gene expression profiling was performed using Affimetrix GeneChip Human Genome U133 Plus 2.0 arrays. Expression profiling results for selected genes were confirmed using qPCR.Infliximab had a significant effect on mRNA expression in treatment responders, with both infliximab dose and duration of treatment having an effect. Genes affected are primarily involved with inflammatory response, cell-mediated immune responses, and cell-to-cell signaling. Unlike responders, non-responders do not effectively modulate T(H₁), T(H₂), and T(H₁₇) pathways. Gene expression can differentiate placebo and infliximab responders.Analysis of mRNA expression in mucosal biopsies following infliximab treatment provided insight into the response to therapy and molecular mechanisms of non-response.

Organ transplant recipients (OTRs) develop multiple aggressive and metastatic non-melanoma skin cancers (NMSCs). Yet, the underlying mechanism remains elusive. Employing a variety of immune-compromised murine models, immunoblotting, immunohistochemical and immunofluorescence techniques, we show that human squamous xenograft tumors in nude mice grow faster and become significantly larger in size following treatment with the immunosuppressive drug, cyclosporine A (CsA). Re-injected tumor cells isolated from CsA-treated xenografts continued to form larger tumors in nude mice than those from vehicle-controls and retained the CsA-signatures of calcineurin signaling inhibition. Similar results were obtained when these tumors were grown in SCID-beige mice or in immuno-competent mice inoculated with syngeinic tumor cells. Consistently, tumors in the CsA group manifested enhanced cellular proliferation and decreased apoptosis. Tumors in CsA-treated animals also showed an augmented epithelial-mesenchymal transition (EMT) characterized by an increased expression of fibronectin, α-SMA, vimentin, N-cadherin, MMP-9/-2, snail and twist with a concomitant decrease in E-cadherin. CsA-treated xenograft tumors manifested increased TGFβ1 expression and TGFβ-dependent signaling characterized by increased nuclear p-Smad 2/3. Our data demonstrate that CsA alters the phenotype of skin SCCs to an invasive and aggressive tumor-type by enhancing expression of proteins regulating EMT acting through the TGFβ1 signaling pathway providing at least one unique mechanism by which multiple aggressive and metastatic NMSCs develop in OTRs.

Background Immunosenescence is the age-related decline and dysfunction of protective immunity leading to a marked increase in the risk of infections, autoimmune disease, and cancer. The majority of studies have focused on immunosenescence in the systemic immune system; information concerning the effect of aging on intestinal immunity is limited. Isolated lymphoid follicles (ILFs) are newly appreciated dynamic intestinal lymphoid structures that arise from nascent lymphoid tissues, or cryptopatches (CP), in response to local inflammatory stimuli. ILFs promote "homeostatic" responses including the production of antigen-specific IgA, thus playing a key role in mucosal immune protection. ILF dysfunction with aging could contribute to immunosenescence of the mucosal system, and accordingly we examined phenotypic and functional aspects of ILFs from young (2 month old) and aged (2 year old) mice. Results We observed that aged mice have increased numbers of ILFs and increased numbers of structures corresponding to an early stage of CPs transforming into ILFs. The cellular composition of ILFs in aged mice is altered with a smaller B-lymphocyte population and an increased T-lymphocyte population. The ILF T-lymphocyte population is notable by the presence of CD4+ CD8αα+ T-lymphocytes, which are absent from the systemic compartment. The smaller B-lymphocyte population in ILFs from aged mice is directly correlated with decreased mRNA and protein expression of CCL20 and CXCL13, two chemokines that play crucial roles in recruiting B-lymphocytes into ILFs. Aged mice had elevated levels of serum and fecal immunoglobulins and despite the decreased B-lymphocyte population, ILFs from aged mice displayed increased IgA production. The immunoglobulin repertoire was skewed in aged mice, and ILFs demonstrated a repertoire usage similar to that of the systemic pool in both young and aged mice. Conclusions Here we observed that ILF development, cellular composition, and immunoglobulin production are altered with aging suggesting that ILF dysfunction contributes to mucosal immunosenescence.

We develop a general method to identify gene networks from pair-wise correlations between genes in a microarray data set and apply it to a public prostate cancer gene expression data from 69 primary prostate tumors. We define the degree of a node as the number of genes significantly associated with the node and identify hub genes as those with the highest degree. The correlation network was pruned using transcription factor binding information in VisANT (http://visant.bu.edu/) as a biological filter. The reliability of hub genes was determined using a strict permutation test. Separate networks for normal prostate samples, and prostate cancer samples from African Americans (AA) and European Americans (EA) were generated and compared. We found that the same hubs control disease progression in AA and EA networks. Combining AA and EA samples, we generated networks for low low (

Single nucleotide polymorphisms (SNPs) in the multiple drug resistance protein 1 (MRP1) and P-glycoprotein 1 (MDR1) genes modulate their ability to mediate drug resistance. We therefore sought to retrospectively evaluate their influence on outcomes in relapsed and/or refractory myeloma patients treated with bortezomib or bortezomib with pegylated liposomal doxorubicin (PLD). The MRP1/R723Q polymorphism was found in five subjects among the 279 patient study population, all of whom received PLD + bortezomib. Its presence was associated with a longer time to progression (TTP; median 330 vs. 129 days; p = 0.0008), progression-free survival (PFS; median 338 vs. 129 days; p = 0.0006), and overall survival (p = 0.0045). MDR1/3435(C > T), which was in Hardy–Weinberg equilibrium, showed a trend of association with PFS (p = 0.0578), response rate (p = 0.0782) and TTP (p = 0.0923) in PLD + bortezomib patients, though no correlation was found in the bortezomib arm. In a recessive genetic model, MDR1/3435 T was significantly associated with a better TTP (p = 0.0405) and PFS (p = 0.0186) in PLD + bortezomib patients. These findings suggest a potential role for MRP1 and MDR1 SNPs in modulating the long-term outcome of relapsed and/or refractory myeloma patients treated with PLD + bortezomib. Moreover, they support prospective studies to determine if such data could be used to tailor therapy to the genetic makeup of individual patients.

Cutaneous Hodgkin lymphoma is infrequent and typically occurs after extensive involvement of the lymph nodes. The condition decreased significantly in incidence in the past two decades, likely owing to the new treatment protocols composed of chemotherapy, radiotherapy and stem cell transplantation. Nevertheless, recognition of this uncommon but significant disease manifestation is important from a prognostic and therapeutic perspective. We are sharing a recent case of Hodgkin lymphoma where the primary presentation appeared as a solitary plaque on the left side of the occipital scalp, clinically suspected to represent a ruptured follicular cyst. The patient underwent excisional biopsy. Histological assessment revealed Hodgkin lymphoma affecting the skin. Radiological studies showed no regional lymphadenopathy. However, two enlarged lymph nodes were identified in the mediastinum and were positron emission tomography avid. The patient underwent systemic treatment without further histopathological examination of these two lymph nodes. Not being clear if these enlarged two lymph nodes were related to his cutaneous disease or not, we cannot be sure if the patient was afflicted either by primary cutaneous Hodgkin lymphoma or by secondary cutaneous involvement because of hematogenous spread. In either case, primary or secondary cutaneous Hodgkin disease is an extreme rarity. The literature is critically reviewed.

Pigmented Paget's disease is a rare variant that is often confused clinically and histologically with melanoma in situ. Herein, we describe a case of pigmented extramammary Paget's disease involving the axilla of a 79-year-old white male thought initially to represent malignant melanoma clinically and histologically. Review of the literature reveals that pigmented variant of Paget's disease, either mammary or extramammary, could be initially misdiagnosed as melanoma unless this entity is considered in the differential diagnosis, and additional confirmatory studies are performed.

Background Genome wide association studies (GWAS) have yielded over 100 genetic loci associated with rheumatoid arthritis (RA). However, the utility of GWAS studies for drug discovery is limited because most GWAS hits do not reside in coding regions and have no known function. Elucidating potential transcriptional regulatory roles of GWAS hits will allow functional annotation of disease-related GWAS loci and lead to better understanding of RA etiology. Objectives To identify potential molecular drivers of RA by mapping expression quantitative trait loci (eQTLs) from gene expression and genotype data from a cohort of RA patients. Methods eQTLs were mapped using whole blood transcriptome data (Affymetrix microarray) from 377 RA patients with inadequate response to methotrexate enrolled in a clinical trial at baseline. Genotypes were generated from whole genome sequencing of DNA from the same subjects. eQTL mapping was performed by linear regression on adjusted data and FDR was estimated with a permutation method separately for local and distant associations. Results We report over 6,000 unique genes with significant eQTLs that represent potential molecular drivers. These eQTLs are enriched for genetic variants associated with RA. Additionally, the genes associated with these RA GWAS loci represent several disease-relevant biological pathways, including antigen presentation and B cell signaling. While there are multiple published eQTL datasets from non-RA cohorts, our analysis suggests that there is utility in detecting eQTLs from disease-relevant cohorts. Indeed, we identified several eQTLs overlapping with RA GWAS loci that have not been reported previously. We also demonstrate that integration with publicly available epigenomics datasets enables elucidation of cell-type-specific relationships. In particular, genes with expression driven by active enhancers in specific immune cell types (e.g., B cells and T helper cells) were identified, generating hypotheses that can be validated experimentally. Conclusions As one of the first studies to detect eQTLs from RA patients, this work provides a valuable resource to better understand the genetic basis for RA and aid in translating genetics research into therapeutic interventions. Overall, this analysis highlights the value of studying peripheral blood given the challenge of obtaining large numbers of synovial tissue biopsies from RA patients. Disclosure of Interest A. Walsh Employee of: Johnson & Johnson, J. Whitaker Employee of: Johnson & Johnson, C. Huang Employee of: Johnson & Johnson, Y. Cherkas Employee of: Johnson & Johnson, S. Lamberth Employee of: Johnson & Johnson, C. Brodmerkel Employee of: Johnson & Johnson, M. Curran Employee of: Johnson & Johnson, R. Dobrin Shareholder of: Johnson & Johnson, Employee of: Johnson & Johnson