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data-emotion="css 1djnqub">.css-1djnqub{display:-ms-grid;display:grid;-ms-grid-gap:2rem;grid-gap:2rem;-ms-grid-columns:repeat(1, minmax(0, 1fr));grid-template-columns:repeat(1, minmax(0, 1fr));}@media screen and (min-width: 1024px){.css-1djnqub{-ms-grid-columns:repeat(3, minmax(0, 1fr));grid-template-columns:repeat(3, minmax(0, 1fr));}}</style><div class="css-1djnqub"><a href="/o/event/61080a2c4517da001280e092?contentLibrary=ESDR&contentLibraryTitle=European Society for Dermatological Research&from=/library/ESDR" style="text-decoration:none;position:relative"><style data-emotion="css 1eo6y6i">.css-1eo6y6i{background-color:var(--chakra-colors-surfacePrimaryFill);background:url(https://storage.googleapis.com/morressier_event_banner_production/cef93879-36ec-4baa-a2f4-40ecb007d03f.png);height:340px;-webkit-background-size:cover;background-size:cover;-webkit-background-position:center;background-position:center;padding-top:var(--chakra-space-12);box-shadow:var(--chakra-shadows-objectDefault);cursor:pointer;border-radius:var(--chakra-radii-base);border:var(--chakra-borders-none);-webkit-transition:box-shadow 0.1s ease;transition:box-shadow 0.1s ease;}.css-1eo6y6i:focus-within{outline-offset:2px;outline-style:solid;outline-color:var(--chakra-colors-attentionSecondaryFill);}.css-1eo6y6i:hover,.css-1eo6y6i[data-hover]{box-shadow:var(--chakra-shadows-objectElevated);}</style><div id="event-card 50TH ANNUAL ESDR MEETING 2021" tabindex="0" class="css-1eo6y6i"><style data-emotion="css 1r0jhqw">.css-1r0jhqw{position:absolute;top:0px;left:0px;width:100%;height:100%;background:var(--chakra-colors-black);opacity:0.5;z-index:1;border-radius:var(--chakra-radii-md);}</style><div class="css-1r0jhqw"></div><style data-emotion="css 1irnppi">.css-1irnppi{position:absolute;bottom:var(--chakra-space-10);width:100%;padding:var(--chakra-space-4);color:var(--chakra-colors-white);z-index:2;}</style><div class="css-1irnppi"><style data-emotion="css 1daojtu">.css-1daojtu{padding:var(--chakra-space-1);font-weight:var(--chakra-fontWeights-bold);font-size:var(--chakra-fontSizes-lg);}</style><p class="chakra-text css-1daojtu">50TH ANNUAL ESDR MEETING 2021</p><style data-emotion="css k008qs">.css-k008qs{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;}</style><div class="css-k008qs"><style data-emotion="css 1pf2w37">.css-1pf2w37{padding:var(--chakra-space-1);}</style><p class="chakra-text css-1pf2w37"> Sep 22-25, 2021</p></div></div></div></a><a href="/o/event/5d4178148fb7e44098e72af1?contentLibrary=ESDR&contentLibraryTitle=European Society for Dermatological Research&from=/library/ESDR" style="text-decoration:none;position:relative"><style data-emotion="css z2da5l">.css-z2da5l{background-color:var(--chakra-colors-surfacePrimaryFill);background:url(https://storage.googleapis.com/dl.morressier.com/banners/esdr2019/2019_ESDR_Meeting_Banner.png);height:340px;-webkit-background-size:cover;background-size:cover;-webkit-background-position:center;background-position:center;padding-top:var(--chakra-space-12);box-shadow:var(--chakra-shadows-objectDefault);cursor:pointer;border-radius:var(--chakra-radii-base);border:var(--chakra-borders-none);-webkit-transition:box-shadow 0.1s ease;transition:box-shadow 0.1s 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1lwfbt2">.css-1lwfbt2{background-color:var(--chakra-colors-surfacePrimaryFill);background:url(https://storage.googleapis.com/morressier_event_banner_production/5f27c0ef-bba2-404b-90c0-d4ed5ccc7cc3.png);height:340px;-webkit-background-size:cover;background-size:cover;-webkit-background-position:center;background-position:center;padding-top:var(--chakra-space-12);box-shadow:var(--chakra-shadows-objectDefault);cursor:pointer;border-radius:var(--chakra-radii-base);border:var(--chakra-borders-none);-webkit-transition:box-shadow 0.1s ease;transition:box-shadow 0.1s ease;}.css-1lwfbt2:focus-within{outline-offset:2px;outline-style:solid;outline-color:var(--chakra-colors-attentionSecondaryFill);}.css-1lwfbt2:hover,.css-1lwfbt2[data-hover]{box-shadow:var(--chakra-shadows-objectElevated);}</style><div id="event-card 1st International Societies for Investigative Dermatology Meeting" tabindex="0" class="css-1lwfbt2"><div class="css-1r0jhqw"></div><div class="css-1irnppi"><p class="chakra-text css-1daojtu">1st International Societies for Investigative Dermatology Meeting</p><div class="css-k008qs"><p class="chakra-text css-1pf2w37"> May 10-13, 2023</p></div></div></div></a><a href="/o/event/62d558b38a1a1f00195adc16?contentLibrary=ESDR&contentLibraryTitle=European Society for Dermatological Research&from=/library/ESDR" style="text-decoration:none;position:relative"><style data-emotion="css e12p2a">.css-e12p2a{background-color:var(--chakra-colors-surfacePrimaryFill);background:url(https://storage.googleapis.com/morressier_event_banner_production/efc75f32-d988-411a-832e-5fdb64fd9c33.png);height:340px;-webkit-background-size:cover;background-size:cover;-webkit-background-position:center;background-position:center;padding-top:var(--chakra-space-12);box-shadow:var(--chakra-shadows-objectDefault);cursor:pointer;border-radius:var(--chakra-radii-base);border:var(--chakra-borders-none);-webkit-transition:box-shadow 0.1s ease;transition:box-shadow 0.1s 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174p7tx">.css-174p7tx{background-color:var(--chakra-colors-surfacePrimaryFill);background:url(https://storage.googleapis.com/dl.morressier.com/banners/esdr2017/2017_ESDR_Meeting_Banner.png);height:340px;-webkit-background-size:cover;background-size:cover;-webkit-background-position:center;background-position:center;padding-top:var(--chakra-space-12);box-shadow:var(--chakra-shadows-objectDefault);cursor:pointer;border-radius:var(--chakra-radii-base);border:var(--chakra-borders-none);-webkit-transition:box-shadow 0.1s ease;transition:box-shadow 0.1s ease;}.css-174p7tx:focus-within{outline-offset:2px;outline-style:solid;outline-color:var(--chakra-colors-attentionSecondaryFill);}.css-174p7tx:hover,.css-174p7tx[data-hover]{box-shadow:var(--chakra-shadows-objectElevated);}</style><div id="event-card The 47th Annual Meeting of the European Society for Dermatological Research" tabindex="0" class="css-174p7tx"><div class="css-1r0jhqw"></div><div class="css-1irnppi"><p class="chakra-text css-1daojtu">The 47th Annual Meeting of the European Society for Dermatological Research</p><div class="css-k008qs"><p class="chakra-text css-1pf2w37"> Sep 27-30, 2017</p><p class="chakra-text css-1pf2w37">| Salzburg, Austria</p></div></div></div></a></div></div></div></div><div style="margin:2em 0"></div></div><div class="Toastify"></div></div></div><span></span><footer class="styles__ContentLibraryFooter-sc-1cxx3pg-0 hhBlrB"><p class="chakra-text styles__LogoContainer-sc-1cxx3pg-1 XDYWb css-0">Powered by <style data-emotion="css 1wunpug">.css-1wunpug{border-radius:small;}</style><a target="_blank" rel="noreferrer" class="chakra-link styles__FooterLink-sc-1cxx3pg-3 lcCJkY css-1wunpug" tabindex="0"><img src="https://next.morressier.com/shared/morressier-logo-black.svg" width="81.32px" height="15.16px"/></a></p><style data-emotion="css k008qs">.css-k008qs{display:-webkit-box;display:-webkit-flex;display:-ms-flexbox;display:flex;}</style><div class="styles__LinksContainer-sc-1cxx3pg-2 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MSCs, multipotent stem cells with immunomodulatory properties have been used to treat immune-mediated inflammatory diseases including rheumatoid arthritis and Crohn disease. We investigated the efficacy and safety of umbilical cord-derived MSCs in 2 adults with severe, multiple biologic-resistant psoriasis. MSCs were infused intravenously at a dose of 2.2–3x106 cells/kg on Day (D) 0 and D7. Both Patient 1(46yo F, baseline PASI 37.8, DLQI 27) and Patient 2 (45yo F, baseline PASI 13.8, DLQI 15) had failed all 4 classes of biologics. At the time of infusion, Patient 1 was unresponsive to etanercept and Patient 2 failing guselkumab. Patient 1: by D7, itch reduced by 50% and by D16, PASI reduced to 23.0 (-39%) and DLQI 10. At D70, PASI maintained at 21.8. Co-morbidities included type 2 diabetes and psoriatic arthritis(PsA). PsA tender joint count at baseline 13; reduced to 9 at D16. Patient 2: by D3, itch reduced by 90%; by D7, PASI reduced to 8.2 (-41%) and DLQI 12. At D28 PASI 1.8 (-87%) and DLQI 8. MSC infusions were well tolerated without adverse events. For Patient 1, immunophenotyping of peripheral blood mononuclear cells at baseline, D7 and D42 post-infusion revealed changes in myeloid and lymphoid cell compartments. Frequency of myeloid dendritic cells(p\u003c0.01 at D7 and D42) and monocytes(p\u003c0.01 at D42) significantly decreased over time, with the latter shifting from classical to non-classical phenotype (p\u003c0.05 at D42). Frequency of CD8+CLA+CD103- skin homing T cells displaying a mixed T1/T17 phenotype significantly increased by D42 (p\u003c0.05), suggesting reduced skin homing by pathogenic T cells. Taken together, MSCs appear to have changed the peripheral immune profile. In conclusion, these data are supportive of immunomodulation by and efficacy of MSCs for patients with severe psoriasis unresponsive to multiple lines of biologics.","doi":"10.26226/m.641999ed5cbd02001a87dad8","public_access_enabled":true,"withdrawn":false,"archive":false,"event":"64122c02bf3c20001b66957a","fileid":"ISID2023-ISID0624","event_short_name":"ISID2023","embargoed":true,"organization_id":"6130f6851d09b6db5da0a40f","authors_v2":[{"id":"576bb67cd462b80292380caf","full_name":"Su Lwin","avatar_url":null,"author_organization":"King's College London","author_organization_id":"5eba80039652df329a982ddc","orcid_id":null}],"web_views":20,"web_bookmarks":0,"web_downloads":6,"objectID":"641999ed5cbd02001a87dad8","_highlightResult":{"title":{"value":"ISID0624 - Clinical and immune analysis of mesenchymal stromal cells (MSCs) for multiple biologic-resistant psoriasis","matchLevel":"none","matchedWords":[]},"abstract_id":{"value":"ISID0624","matchLevel":"none","matchedWords":[]},"abstract":{"value":"Biologics have transformed the management of moderate-to-severe psoriasis; however, none are curative, and an increasing number of patients have failed all available classes. MSCs, multipotent stem cells with immunomodulatory properties have been used to treat immune-mediated inflammatory diseases including rheumatoid arthritis and Crohn disease. We investigated the efficacy and safety of umbilical cord-derived MSCs in 2 adults with severe, multiple biologic-resistant psoriasis. MSCs were infused intravenously at a dose of 2.2–3x106 cells/kg on Day (D) 0 and D7. Both Patient 1(46yo F, baseline PASI 37.8, DLQI 27) and Patient 2 (45yo F, baseline PASI 13.8, DLQI 15) had failed all 4 classes of biologics. At the time of infusion, Patient 1 was unresponsive to etanercept and Patient 2 failing guselkumab. Patient 1: by D7, itch reduced by 50% and by D16, PASI reduced to 23.0 (-39%) and DLQI 10. At D70, PASI maintained at 21.8. Co-morbidities included type 2 diabetes and psoriatic arthritis(PsA). PsA tender joint count at baseline 13; reduced to 9 at D16. Patient 2: by D3, itch reduced by 90%; by D7, PASI reduced to 8.2 (-41%) and DLQI 12. At D28 PASI 1.8 (-87%) and DLQI 8. MSC infusions were well tolerated without adverse events. For Patient 1, immunophenotyping of peripheral blood mononuclear cells at baseline, D7 and D42 post-infusion revealed changes in myeloid and lymphoid cell compartments. Frequency of myeloid dendritic cells(p\u003c0.01 at D7 and D42) and monocytes(p\u003c0.01 at D42) significantly decreased over time, with the latter shifting from classical to non-classical phenotype (p\u003c0.05 at D42). Frequency of CD8+CLA+CD103- skin homing T cells displaying a mixed T1/T17 phenotype significantly increased by D42 (p\u003c0.05), suggesting reduced skin homing by pathogenic T cells. Taken together, MSCs appear to have changed the peripheral immune profile. In conclusion, these data are supportive of immunomodulation by and efficacy of MSCs for patients with severe psoriasis unresponsive to multiple lines of biologics.","matchLevel":"none","matchedWords":[]},"event_name":{"value":"1st International Societies for Investigative Dermatology Meeting","matchLevel":"none","matchedWords":[]},"event_short_name":{"value":"ISID2023","matchLevel":"none","matchedWords":[]},"author_names":[{"value":"Su Lwin","matchLevel":"none","matchedWords":[]}],"author_organizations":[{"value":"King's College London","matchLevel":"none","matchedWords":[]}],"keywords":[{"value":"psoriasis","matchLevel":"none","matchedWords":[]},{"value":" Stem Cells","matchLevel":"none","matchedWords":[]},{"value":" Immunology","matchLevel":"none","matchedWords":[]},{"value":"p","matchLevel":"none","matchedWords":[]},{"value":"a","matchLevel":"none","matchedWords":[]},{"value":"adalimumab","matchLevel":"none","matchedWords":[]},{"value":"amino acids, peptides, and 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cord","matchLevel":"none","matchedWords":[]}]},"thumb_url":"https://thesummit-production.s3.eu-central-1.amazonaws.com/ISID2023/thumbnails/medium/ISID2023-ISID0624-0.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256\u0026X-Amz-Credential=AKIAYW6F77ISNQMTJJGK%2F20241123%2Feu-central-1%2Fs3%2Faws4_request\u0026X-Amz-Date=20241123T112436Z\u0026X-Amz-Expires=14400\u0026X-Amz-Signature=69c80793e9c09c56e3d7d69899f20d74abfe331b04ad2f9f0272eec4b7e060b4\u0026X-Amz-SignedHeaders=host","thumb_url_medium":"https://thesummit-production.s3.eu-central-1.amazonaws.com/ISID2023/thumbnails/large/ISID2023-ISID0624-0.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256\u0026X-Amz-Credential=AKIAYW6F77ISNQMTJJGK%2F20241123%2Feu-central-1%2Fs3%2Faws4_request\u0026X-Amz-Date=20241123T112436Z\u0026X-Amz-Expires=14400\u0026X-Amz-Signature=08e0a2d0ec586215e4797e278b5eb94f6fbaa36a1e0da82ae22eb1dcded92819\u0026X-Amz-SignedHeaders=host","thumb_url_large":"https://thesummit-production.s3.eu-central-1.amazonaws.com/ISID2023/thumbnails/retina/ISID2023-ISID0624-0.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256\u0026X-Amz-Credential=AKIAYW6F77ISNQMTJJGK%2F20241123%2Feu-central-1%2Fs3%2Faws4_request\u0026X-Amz-Date=20241123T112436Z\u0026X-Amz-Expires=14400\u0026X-Amz-Signature=72d4718a17f72cd9bc53d70a0cc3a6da6c9ec75d4d6f98eb319149f98a57e82a\u0026X-Amz-SignedHeaders=host","_id":"641999ed5cbd02001a87dad8"},"element_order":0},{"element":{"poster_id":"64199a1a96661e001462d10c","title":"ISID1629 - High-throughput T cell receptor sequencing aids in the diagnosis of CTCL","abstract_id":"ISID1629","uploaded_at":null,"upload_month":null,"upload_year":null,"abstract":"Cutaneous T-cell lymphomas (CTCL) are difficult to diagnose and may resemble benign inflammatory dermatoses (BID). Hence, diagnosis requires consideration of clinical, histopathologic, and molecular studies. Though, widely used molecular studies rely on the T cell receptor g (TCRg) polymerase chain reaction (PCR) to detect a T cell clone, it is reportedly positive in ~50% of early CTCL cases. High throughput TCR sequencing (HTS) of the TCRb gene (ImmunoSEQ®) in a prior CTCL cohort has demonstrated it is more sensitive and specific than TCRg PCR and discriminates CTCL from BID. We evaluated the performance of clonoSEQ®, a clinically available assay for the detection of a dominate clone by HTS of the TCRb gene in a cohort of patients with suspected CTCL referred to the multi-disciplinary cutaneous lymphoma clinic at DFCI from 2016-2021. A total of 151 patients underwent clonoSEQ® from skin biopsies, of which 82 were considered by clinicians to meet criteria for CTCL based on all available data. Among CTCL patients who also underwent TCRg PCR (n= 48), 97% had a positive clone by clonoSEQ® compared to 79% who had a positive clone by TCRg PCR. A single patient was deemed by a clinician to have CTCL, despite the absence of a clone by clonoSEQ® was later re-diagnosed with tinea corporis and in complete remission of their skin eruption following a course of topical anti-fungals. Among patients with CTCL, 44 had 1 dominate clone, 38 had 2 dominate clones, 6 had 3 dominate clone, 1 had 4 dominate clone. Given that an individual T cell may have biallelic rearrangement of the TCRB gene (i.e. two dominate clones may derive from one T cell) we observed that while CTCL is largely a monoclonal neoplastic process, select individuals may have oligoclonal T cells. It is not clear whether additional clones are neoplastic or reactive (e.g. anti-tumor T cells).","doi":"10.26226/m.64199a1a96661e001462d10c","public_access_enabled":true,"withdrawn":false,"archive":false,"event":"64122c02bf3c20001b66957a","fileid":"ISID2023-ISID1629","event_short_name":"ISID2023","embargoed":true,"organization_id":"6130f6851d09b6db5da0a40f","authors_v2":[{"id":"64199991c5146900127c836c","full_name":"Nana Ama Adjei-Frimpong","avatar_url":null,"author_organization":"Harvard University","author_organization_id":null,"orcid_id":null}],"web_views":10,"web_bookmarks":0,"web_downloads":3,"objectID":"64199a1a96661e001462d10c","_highlightResult":{"title":{"value":"ISID1629 - High-throughput T cell receptor sequencing aids in the diagnosis of CTCL","matchLevel":"none","matchedWords":[]},"abstract_id":{"value":"ISID1629","matchLevel":"none","matchedWords":[]},"abstract":{"value":"Cutaneous T-cell lymphomas (CTCL) are difficult to diagnose and may resemble benign inflammatory dermatoses (BID). Hence, diagnosis requires consideration of clinical, histopathologic, and molecular studies. Though, widely used molecular studies rely on the T cell receptor g (TCRg) polymerase chain reaction (PCR) to detect a T cell clone, it is reportedly positive in ~50% of early CTCL cases. High throughput TCR sequencing (HTS) of the TCRb gene (ImmunoSEQ®) in a prior CTCL cohort has demonstrated it is more sensitive and specific than TCRg PCR and discriminates CTCL from BID. We evaluated the performance of clonoSEQ®, a clinically available assay for the detection of a dominate clone by HTS of the TCRb gene in a cohort of patients with suspected CTCL referred to the multi-disciplinary cutaneous lymphoma clinic at DFCI from 2016-2021. A total of 151 patients underwent clonoSEQ® from skin biopsies, of which 82 were considered by clinicians to meet criteria for CTCL based on all available data. Among CTCL patients who also underwent TCRg PCR (n= 48), 97% had a positive clone by clonoSEQ® compared to 79% who had a positive clone by TCRg PCR. A single patient was deemed by a clinician to have CTCL, despite the absence of a clone by clonoSEQ® was later re-diagnosed with tinea corporis and in complete remission of their skin eruption following a course of topical anti-fungals. Among patients with CTCL, 44 had 1 dominate clone, 38 had 2 dominate clones, 6 had 3 dominate clone, 1 had 4 dominate clone. Given that an individual T cell may have biallelic rearrangement of the TCRB gene (i.e. two dominate clones may derive from one T cell) we observed that while CTCL is largely a monoclonal neoplastic process, select individuals may have oligoclonal T cells. It is not clear whether additional clones are neoplastic or reactive (e.g. anti-tumor T cells).","matchLevel":"none","matchedWords":[]},"event_name":{"value":"1st International Societies for Investigative Dermatology Meeting","matchLevel":"none","matchedWords":[]},"event_short_name":{"value":"ISID2023","matchLevel":"none","matchedWords":[]},"author_names":[{"value":"Nana Ama Adjei-Frimpong","matchLevel":"none","matchedWords":[]}],"author_organizations":[{"value":"Harvard University","matchLevel":"none","matchedWords":[]}],"keywords":[{"value":"Cutaneous T Cell Lymphoma (CTCL)","matchLevel":"none","matchedWords":[]},{"value":" T Lymphocytes","matchLevel":"none","matchedWords":[]},{"value":" T Cells","matchLevel":"none","matchedWords":[]},{"value":"nan","matchLevel":"none","matchedWords":[]},{"value":"","matchLevel":"none","matchedWords":[]},{"value":")","matchLevel":"none","matchedWords":[]},{"value":"c","matchLevel":"none","matchedWords":[]},{"value":"l","matchLevel":"none","matchedWords":[]},{"value":"t","matchLevel":"none","matchedWords":[]},{"value":"a","matchLevel":"none","matchedWords":[]},{"value":"bacterial infections and mycoses","matchLevel":"none","matchedWords":[]},{"value":"blood","matchLevel":"none","matchedWords":[]},{"value":"blood cells","matchLevel":"none","matchedWords":[]},{"value":"cells","matchLevel":"none","matchedWords":[]},{"value":"dermatomycoses","matchLevel":"none","matchedWords":[]},{"value":"diagnosis","matchLevel":"none","matchedWords":[]},{"value":"e","matchLevel":"none","matchedWords":[]},{"value":"genetic techniques","matchLevel":"none","matchedWords":[]},{"value":"h","matchLevel":"none","matchedWords":[]},{"value":"hemic and immune 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infectious","matchLevel":"none","matchedWords":[]},{"value":"t","matchLevel":"none","matchedWords":[]},{"value":"tinea","matchLevel":"none","matchedWords":[]},{"value":"u","matchLevel":"none","matchedWords":[]},{"value":"y","matchLevel":"none","matchedWords":[]}]},"thumb_url":"https://thesummit-production.s3.eu-central-1.amazonaws.com/ISID2023/thumbnails/medium/ISID2023-ISID1629-0.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256\u0026X-Amz-Credential=AKIAYW6F77ISNQMTJJGK%2F20241123%2Feu-central-1%2Fs3%2Faws4_request\u0026X-Amz-Date=20241123T112436Z\u0026X-Amz-Expires=14400\u0026X-Amz-Signature=2ef5c7f90b85393152ef661099b7e59a8c85bd39b597abc9bf6073ea7d09df44\u0026X-Amz-SignedHeaders=host","thumb_url_medium":"https://thesummit-production.s3.eu-central-1.amazonaws.com/ISID2023/thumbnails/large/ISID2023-ISID1629-0.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256\u0026X-Amz-Credential=AKIAYW6F77ISNQMTJJGK%2F20241123%2Feu-central-1%2Fs3%2Faws4_request\u0026X-Amz-Date=20241123T112436Z\u0026X-Amz-Expires=14400\u0026X-Amz-Signature=9be275f67053dffdbfe9ae8af25481d0d3ae2d42cdacf8f50da5cac5abe00ad2\u0026X-Amz-SignedHeaders=host","thumb_url_large":"https://thesummit-production.s3.eu-central-1.amazonaws.com/ISID2023/thumbnails/retina/ISID2023-ISID1629-0.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256\u0026X-Amz-Credential=AKIAYW6F77ISNQMTJJGK%2F20241123%2Feu-central-1%2Fs3%2Faws4_request\u0026X-Amz-Date=20241123T112436Z\u0026X-Amz-Expires=14400\u0026X-Amz-Signature=284bef55e4744508f4f0f7cd1b6c2e3a0409745e48a4389e2df1551860944c41\u0026X-Amz-SignedHeaders=host","_id":"64199a1a96661e001462d10c"},"element_order":1},{"element":{"poster_id":"641999f8b9b42e0013e5936e","title":"ISID0872 - One-step correction through CRISPR/Cas9-mediated HDR and reprograming in induced pluripotent stem cells from a patient with a highly recurrent mutation in COL7A1","abstract_id":"ISID0872","uploaded_at":null,"upload_month":null,"upload_year":null,"abstract":"Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare and severe genetic skin disease responsible for blistering of the skin and mucosa after minor trauma. RDEB is caused by a wide variety of mutations in COL7A1 encoding type VII collagen, the major component of anchoring fibrils which form key attachment structures for dermal-epidermal adhesion. In our study, we investigated the therapeutic potential of combined CRISPR/Cas-9-based correction and reprogramming of primary RDEB-Fibroblasts (Fs) harboring the highly recurrent c.425A\u003eG (p.Lys142Arg) mutation in exon 3 of COL7A1. To achieve genetic correction, we designed a gRNA specifically targeting the mutation which activity was estimated to be 70% in RDEB-Fs. Combined correction and iPSCs reprogramming were carried out in one step. iPSC reprogramming was performed by transfecting an integration-free mRNA and microRNA cocktail encoding reprogramming factors (OCT4, SOX2, cMYC, KLF4, NANOG, LIN28 and miR-367/302s) under feeder-free conditions. First, Cas9 mRNA, gRNA and the 100nt donor template ssODN were delivered by a single lipofectamin-based transfection into primary RDEB-Fs. Then reprogramming RNA transfections we performed every other day for 14 days. At day 18, iPSCs clones were selected and characterized for their pluripotency and differentiation capacity into three germ layers. We were able to differentiate them into cell types of interest: i) Fs expressing specific CD surface markers, CD10, CD73, CD90, COL1 and COL3 and ii) Keratinocytes expressing the basal keratins KRT5 and KRT14. Finally, gene-correction in RDEB-iPSCs was scored at the genomic DNA level by Taqman-ddPCR and was estimated to be up to 70%. Demonstration of functional correction of type VII collagen through the generation and analysis of 3D-skin equivalents is ongoing in the perspective of developing of transplantable skin models suitable for the clinical application.","doi":null,"public_access_enabled":true,"withdrawn":false,"archive":false,"event":"64122c02bf3c20001b66957a","fileid":"ISID2023-ISID0872","event_short_name":"ISID2023","embargoed":true,"organization_id":"6130f6851d09b6db5da0a40f","authors_v2":[{"id":"576bb67d8fb7e44098e72e47","full_name":"Araksya Izmiryan","avatar_url":null,"author_organization":"Inserm UMR1163 - Institut Imagine","author_organization_id":null,"orcid_id":null}],"web_views":16,"web_bookmarks":0,"web_downloads":4,"objectID":"641999f8b9b42e0013e5936e","_highlightResult":{"title":{"value":"ISID0872 - One-step correction through CRISPR/Cas9-mediated HDR and reprograming in induced pluripotent stem cells from a patient with a highly recurrent mutation in COL7A1","matchLevel":"none","matchedWords":[]},"abstract_id":{"value":"ISID0872","matchLevel":"none","matchedWords":[]},"abstract":{"value":"Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare and severe genetic skin disease responsible for blistering of the skin and mucosa after minor trauma. RDEB is caused by a wide variety of mutations in COL7A1 encoding type VII collagen, the major component of anchoring fibrils which form key attachment structures for dermal-epidermal adhesion. In our study, we investigated the therapeutic potential of combined CRISPR/Cas-9-based correction and reprogramming of primary RDEB-Fibroblasts (Fs) harboring the highly recurrent c.425A\u003eG (p.Lys142Arg) mutation in exon 3 of COL7A1. To achieve genetic correction, we designed a gRNA specifically targeting the mutation which activity was estimated to be 70% in RDEB-Fs. Combined correction and iPSCs reprogramming were carried out in one step. iPSC reprogramming was performed by transfecting an integration-free mRNA and microRNA cocktail encoding reprogramming factors (OCT4, SOX2, cMYC, KLF4, NANOG, LIN28 and miR-367/302s) under feeder-free conditions. First, Cas9 mRNA, gRNA and the 100nt donor template ssODN were delivered by a single lipofectamin-based transfection into primary RDEB-Fs. Then reprogramming RNA transfections we performed every other day for 14 days. At day 18, iPSCs clones were selected and characterized for their pluripotency and differentiation capacity into three germ layers. We were able to differentiate them into cell types of interest: i) Fs expressing specific CD surface markers, CD10, CD73, CD90, COL1 and COL3 and ii) Keratinocytes expressing the basal keratins KRT5 and KRT14. Finally, gene-correction in RDEB-iPSCs was scored at the genomic DNA level by Taqman-ddPCR and was estimated to be up to 70%. Demonstration of functional correction of type VII collagen through the generation and analysis of 3D-skin equivalents is ongoing in the perspective of developing of transplantable skin models suitable for the clinical application.","matchLevel":"none","matchedWords":[]},"event_name":{"value":"1st International Societies for Investigative Dermatology Meeting","matchLevel":"none","matchedWords":[]},"event_short_name":{"value":"ISID2023","matchLevel":"none","matchedWords":[]},"author_names":[{"value":"Araksya Izmiryan","matchLevel":"none","matchedWords":[]}],"author_organizations":[{"value":"Inserm UMR1163 - Institut Imagine","matchLevel":"none","matchedWords":[]}],"keywords":[{"value":"epidermolysis bullosa","matchLevel":"none","matchedWords":[]},{"value":" Genetic Diseases","matchLevel":"none","matchedWords":[]},{"value":" Induced Pluripotent Stem (iPS) 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- Clinical features, time to diagnosis, and time to comorbidity screening in a diverse cohort of patients with clinically amyopathic dermatomyositis","abstract_id":"ISID0510","uploaded_at":null,"upload_month":null,"upload_year":null,"abstract":"Clinically amyopathic dermatomyositis (CADM) can be challenging to diagnose due to clinicopathologic overlap with other skin rashes and potentially subtle examination findings in patients with darker skin. The degree to which a patient’s skin color impacts clinical presentation of CADM, time to diagnosis, and screening for comorbidities such as malignancy and interstitial lung disease (ILD) has not been studied in-depth in dermatomyositis. To investigate this question, we identified 75 patients with CADM at Johns Hopkins from 2000-present and retrospectively gathered data on Fitzpatrick skin type, clinical presentation, time from symptoms to diagnosis, and time from diagnosis to cancer and ILD screening. 54 patients had Fitzpatrick skin type I-III and 21 patients had skin type IV-VI. Overall time to diagnosis was 17.9 months (range 0.2-120 months) and overall time to cancer screening was 52 days (range 0-300 days). 5 patients had an associated systemic malignancy. Skin findings in patients with Fitzpatrick skin type I-III vs. IV-VI included: heliotrope rash in 52% vs. 65% (p=0.43), Gottron papules in 76% vs. 75% (p=1), Gottron sign in 50% vs. 60% (p=0.6), Holster sign in 15% vs. 30% (p=0.18), V-neck sign in 50% vs. 60% (p=0.6), Shawl sign in 44% vs. 70% (p=0.07), periungual erythema in 80% vs. 75% (p=0.75), mechanic’s hands in 30% vs. 35% (p=0.78), scalp rash 33% vs. 15% (p=0.15), calcinosis cutis in 17% vs. 15% (p=1), and skin ulcerations in 11% vs. 20% (p=0.44). In patients with Fitzpatrick type I-III vs. IV-VI, time to diagnosis was 19 months vs. 16 months (p=0.79), time to cancer screening was 52.6 vs. 54.3 days (p=1), and time to ILD screening was 285 days vs. 94 days (p=0.29). Overall, patients presented with similar skin findings and time to diagnosis and screening regardless of skin type. We are currently investigating for factors related to unusual clinical presentations and delayed diagnosis and screening in individual patients.","doi":null,"public_access_enabled":true,"withdrawn":false,"archive":false,"event":"64122c02bf3c20001b66957a","fileid":"ISID2023-ISID0510","event_short_name":"ISID2023","embargoed":true,"organization_id":"6130f6851d09b6db5da0a40f","authors_v2":[{"id":"6419999088811f001400f93e","full_name":"David Weiner","avatar_url":null,"author_organization":"Johns Hopkins University","author_organization_id":null,"orcid_id":null}],"web_views":1,"web_bookmarks":0,"web_downloads":0,"objectID":"641999e8c5146900127c8463","_highlightResult":{"title":{"value":"ISID0510 - Clinical features, time to diagnosis, and time to comorbidity screening in a diverse cohort of patients with clinically amyopathic dermatomyositis","matchLevel":"none","matchedWords":[]},"abstract_id":{"value":"ISID0510","matchLevel":"none","matchedWords":[]},"abstract":{"value":"Clinically amyopathic dermatomyositis (CADM) can be challenging to diagnose due to clinicopathologic overlap with other skin rashes and potentially subtle examination findings in patients with darker skin. The degree to which a patient’s skin color impacts clinical presentation of CADM, time to diagnosis, and screening for comorbidities such as malignancy and interstitial lung disease (ILD) has not been studied in-depth in dermatomyositis. To investigate this question, we identified 75 patients with CADM at Johns Hopkins from 2000-present and retrospectively gathered data on Fitzpatrick skin type, clinical presentation, time from symptoms to diagnosis, and time from diagnosis to cancer and ILD screening. 54 patients had Fitzpatrick skin type I-III and 21 patients had skin type IV-VI. Overall time to diagnosis was 17.9 months (range 0.2-120 months) and overall time to cancer screening was 52 days (range 0-300 days). 5 patients had an associated systemic malignancy. Skin findings in patients with Fitzpatrick skin type I-III vs. IV-VI included: heliotrope rash in 52% vs. 65% (p=0.43), Gottron papules in 76% vs. 75% (p=1), Gottron sign in 50% vs. 60% (p=0.6), Holster sign in 15% vs. 30% (p=0.18), V-neck sign in 50% vs. 60% (p=0.6), Shawl sign in 44% vs. 70% (p=0.07), periungual erythema in 80% vs. 75% (p=0.75), mechanic’s hands in 30% vs. 35% (p=0.78), scalp rash 33% vs. 15% (p=0.15), calcinosis cutis in 17% vs. 15% (p=1), and skin ulcerations in 11% vs. 20% (p=0.44). In patients with Fitzpatrick type I-III vs. IV-VI, time to diagnosis was 19 months vs. 16 months (p=0.79), time to cancer screening was 52.6 vs. 54.3 days (p=1), and time to ILD screening was 285 days vs. 94 days (p=0.29). Overall, patients presented with similar skin findings and time to diagnosis and screening regardless of skin type. We are currently investigating for factors related to unusual clinical presentations and delayed diagnosis and screening in individual patients.","matchLevel":"none","matchedWords":[]},"event_name":{"value":"1st International Societies for Investigative Dermatology Meeting","matchLevel":"none","matchedWords":[]},"event_short_name":{"value":"ISID2023","matchLevel":"none","matchedWords":[]},"author_names":[{"value":"David Weiner","matchLevel":"none","matchedWords":[]}],"author_organizations":[{"value":"Johns Hopkins University","matchLevel":"none","matchedWords":[]}],"keywords":[{"value":"autoimmunity","matchLevel":"none","matchedWords":[]},{"value":"A","matchLevel":"none","matchedWords":[]},{"value":"autoimmunity","matchLevel":"none","matchedWords":[]},{"value":"body regions","matchLevel":"none","matchedWords":[]},{"value":"calcinosis","matchLevel":"none","matchedWords":[]},{"value":"calcium metabolism disorders","matchLevel":"none","matchedWords":[]},{"value":"cancer","matchLevel":"none","matchedWords":[]},{"value":"color","matchLevel":"none","matchedWords":[]},{"value":"connective tissue diseases","matchLevel":"none","matchedWords":[]},{"value":"dermatomyositis","matchLevel":"none","matchedWords":[]},{"value":"diagnosis","matchLevel":"none","matchedWords":[]},{"value":"disease","matchLevel":"none","matchedWords":[]},{"value":"erythema","matchLevel":"none","matchedWords":[]},{"value":"head","matchLevel":"none","matchedWords":[]},{"value":"i","matchLevel":"none","matchedWords":[]},{"value":"immune system phenomena","matchLevel":"none","matchedWords":[]},{"value":"immunity","matchLevel":"none","matchedWords":[]},{"value":"lung","matchLevel":"none","matchedWords":[]},{"value":"m","matchLevel":"none","matchedWords":[]},{"value":"metabolic diseases","matchLevel":"none","matchedWords":[]},{"value":"muscular diseases","matchLevel":"none","matchedWords":[]},{"value":"musculoskeletal diseases","matchLevel":"none","matchedWords":[]},{"value":"myositis","matchLevel":"none","matchedWords":[]},{"value":"n","matchLevel":"none","matchedWords":[]},{"value":"nervous system diseases","matchLevel":"none","matchedWords":[]},{"value":"neuromuscular diseases","matchLevel":"none","matchedWords":[]},{"value":"nutritional and metabolic diseases","matchLevel":"none","matchedWords":[]},{"value":"o","matchLevel":"none","matchedWords":[]},{"value":"pathologic processes","matchLevel":"none","matchedWords":[]},{"value":"pathological conditions, signs and symptoms","matchLevel":"none","matchedWords":[]},{"value":"polymyositis","matchLevel":"none","matchedWords":[]},{"value":"respiratory system","matchLevel":"none","matchedWords":[]},{"value":"scalp","matchLevel":"none","matchedWords":[]},{"value":"signs and symptoms","matchLevel":"none","matchedWords":[]},{"value":"skin and connective tissue diseases","matchLevel":"none","matchedWords":[]},{"value":"skin diseases","matchLevel":"none","matchedWords":[]},{"value":"skin manifestations","matchLevel":"none","matchedWords":[]},{"value":"t","matchLevel":"none","matchedWords":[]},{"value":"u","matchLevel":"none","matchedWords":[]},{"value":"y","matchLevel":"none","matchedWords":[]}]},"thumb_url":"https://thesummit-production.s3.eu-central-1.amazonaws.com/ISID2023/thumbnails/medium/ISID2023-ISID0510-0.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256\u0026X-Amz-Credential=AKIAYW6F77ISNQMTJJGK%2F20241123%2Feu-central-1%2Fs3%2Faws4_request\u0026X-Amz-Date=20241123T112436Z\u0026X-Amz-Expires=14400\u0026X-Amz-Signature=78ab696f1e465f5307cf1b3999eda908210655b18ecd7d0659e0c62fded6e9eb\u0026X-Amz-SignedHeaders=host","thumb_url_medium":"https://thesummit-production.s3.eu-central-1.amazonaws.com/ISID2023/thumbnails/large/ISID2023-ISID0510-0.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256\u0026X-Amz-Credential=AKIAYW6F77ISNQMTJJGK%2F20241123%2Feu-central-1%2Fs3%2Faws4_request\u0026X-Amz-Date=20241123T112436Z\u0026X-Amz-Expires=14400\u0026X-Amz-Signature=6479c60e3ee1252bc13e30710b2992ad3269c12391c0ff92d698775578fd461c\u0026X-Amz-SignedHeaders=host","thumb_url_large":"https://thesummit-production.s3.eu-central-1.amazonaws.com/ISID2023/thumbnails/retina/ISID2023-ISID0510-0.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256\u0026X-Amz-Credential=AKIAYW6F77ISNQMTJJGK%2F20241123%2Feu-central-1%2Fs3%2Faws4_request\u0026X-Amz-Date=20241123T112436Z\u0026X-Amz-Expires=14400\u0026X-Amz-Signature=baae688e118385d9558b3bdc9792fae0ef756527e1b7c3061ce778686eb4666b\u0026X-Amz-SignedHeaders=host","_id":"641999e8c5146900127c8463"},"element_order":3},{"element":{"poster_id":"64199a1460d56100127c2b38","title":"ISID1489 - TRPV4 promotes cutaneous wound healing by enhancing keratinocyte migration via MAPK signaling and regulating TGF-β induced differentiation in fibroblasts","abstract_id":"ISID1489","uploaded_at":null,"upload_month":null,"upload_year":null,"abstract":"Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable non-selective cation channel in TRP family and highly expressed in skin tissue. Several studies have demonstrated its multiple function in the regulation of inflammation, fibrosis and tumor growth. We recently identified that TRPV4 expression was increased in wounded skin area. However, the role of TRPV4 in cutaneous wound healing was not well characterized, therefore we aimed to investigate it. Cutaneous wound healing experiment was performed in WT and TRPV4 KO mice. Skin tissues from wounded area were collected for histological and biochemical studies. Mouse primary keratinocytes derived from WT and TRPV4 KO mice and NIH3T3 cells were used in vitro study. Wound healing was significantly delayed in TRPV4 KO mice from 2 to 4 days after wounding (p\u003c0.01) compared with WT mice. Pathological studies revealed the impaired re-epithelialization and the formation of granulation tissue in TRPV4 KO mice. Protein and mRNA levels of type I collagen and αSMA expression in the wounded area were decreased in TRPV4 KO mice (p\u003c0.05). In the in vitro study, the migrative capacity was impaired in mouse primary keratinocytes from TRPV4 KO mice compared with WT mice (p\u003c0.01). Immunoblotting assay revealed that scratch stimulus enhanced the ERK phosphorylation level was suppressed by TRPV4 antagonist (HC-067047) administration. Elevated mRNA expression level of COL1A1 and ACTA2 in TGF-β stimulated NIH3T3 cells were suppressed by TRPV4 antagonist treatment. In conclusion, TRPV4 promotes keratinocytes migration via activation of MAPK signaling pathways and TGF-β induced myofibroblasts differentiation, resulting in accelerated wound healing. The activation of TRPV4 channels may have a therapeutic potential for intractable wounds.","doi":null,"public_access_enabled":true,"withdrawn":false,"archive":false,"event":"64122c02bf3c20001b66957a","fileid":"ISID2023-ISID1489","event_short_name":"ISID2023","embargoed":true,"organization_id":"6130f6851d09b6db5da0a40f","authors_v2":[{"id":"6419999260d56100127c265b","full_name":"Sahori Yamazaki","avatar_url":null,"author_organization":"Gunma Daigaku","author_organization_id":null,"orcid_id":null}],"web_views":21,"web_bookmarks":0,"web_downloads":7,"objectID":"64199a1460d56100127c2b38","_highlightResult":{"title":{"value":"ISID1489 - TRPV4 promotes cutaneous wound healing by enhancing keratinocyte migration via MAPK signaling and regulating TGF-β induced differentiation in fibroblasts","matchLevel":"none","matchedWords":[]},"abstract_id":{"value":"ISID1489","matchLevel":"none","matchedWords":[]},"abstract":{"value":"Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable non-selective cation channel in TRP family and highly expressed in skin tissue. Several studies have demonstrated its multiple function in the regulation of inflammation, fibrosis and tumor growth. We recently identified that TRPV4 expression was increased in wounded skin area. However, the role of TRPV4 in cutaneous wound healing was not well characterized, therefore we aimed to investigate it. Cutaneous wound healing experiment was performed in WT and TRPV4 KO mice. Skin tissues from wounded area were collected for histological and biochemical studies. Mouse primary keratinocytes derived from WT and TRPV4 KO mice and NIH3T3 cells were used in vitro study. Wound healing was significantly delayed in TRPV4 KO mice from 2 to 4 days after wounding (p\u003c0.01) compared with WT mice. Pathological studies revealed the impaired re-epithelialization and the formation of granulation tissue in TRPV4 KO mice. Protein and mRNA levels of type I collagen and αSMA expression in the wounded area were decreased in TRPV4 KO mice (p\u003c0.05). In the in vitro study, the migrative capacity was impaired in mouse primary keratinocytes from TRPV4 KO mice compared with WT mice (p\u003c0.01). Immunoblotting assay revealed that scratch stimulus enhanced the ERK phosphorylation level was suppressed by TRPV4 antagonist (HC-067047) administration. Elevated mRNA expression level of COL1A1 and ACTA2 in TGF-β stimulated NIH3T3 cells were suppressed by TRPV4 antagonist treatment. In conclusion, TRPV4 promotes keratinocytes migration via activation of MAPK signaling pathways and TGF-β induced myofibroblasts differentiation, resulting in accelerated wound healing. The activation of TRPV4 channels may have a therapeutic potential for intractable wounds.","matchLevel":"none","matchedWords":[]},"event_name":{"value":"1st International Societies for Investigative Dermatology Meeting","matchLevel":"none","matchedWords":[]},"event_short_name":{"value":"ISID2023","matchLevel":"none","matchedWords":[]},"author_names":[{"value":"Sahori Yamazaki","matchLevel":"none","matchedWords":[]}],"author_organizations":[{"value":"Gunma Daigaku","matchLevel":"none","matchedWords":[]}],"keywords":[{"value":"wound healing","matchLevel":"none","matchedWords":[]},{"value":" Tissue Regeneration","matchLevel":"none","matchedWords":[]},{"value":" Models, Mouse","matchLevel":"none","matchedWords":[]},{"value":"nan","matchLevel":"none","matchedWords":[]},{"value":"h","matchLevel":"none","matchedWords":[]},{"value":"w","matchLevel":"none","matchedWords":[]},{"value":"a","matchLevel":"none","matchedWords":[]},{"value":"amino acids, peptides, and 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- Single-cell RNA sequencing defines disease-specific differences between prurigo nodularis and atopic dermatitis","abstract_id":"ISID0150","uploaded_at":null,"upload_month":null,"upload_year":null,"abstract":"Prurigo nodularis (PN) is an inflammatory skin disease that is maintained by a chronic itch-scratch cycle likely rooted in neuro-immunological dysregulation with an unknown origin. The condition may be associated with atopy in some patients, and there are now promising therapeutic results from blocking type-2 cytokines such as IL-4, IL-13 and IL-31 in the clinics. Nevertheless, underlying pathomechanisms as well as the molecular relationship with atopy remain ill-defined. Here, we profiled skin lesions from patients with PN in comparison to atopic dermatitis (AD) and healthy controls (HC) using single-cell RNA sequencing combined with T-cell receptor (TCR) sequencing. We found type-2 immune skewing in both PN and AD as evidenced by CD4+ helper T cells expressing IL13. However, only AD harbored an additional, oligoclonally expanded CD8A+ IL9R+ IL13+ cytotoxic T cell population, and immune activation pathways were highly upregulated in AD, but less so in PN. Conversely, PN showed signatures of extracellular matrix organization, collagen synthesis and fibrosis, including a unique population of CXCL14- IL24+ secretory-papillary fibroblasts. Besides known itch mediators such as IL31 and OSM, we detected high levels of neuromedin B (NMB) in various cell types of PN but not AD, with receptors detectable on some nerve endings. These data show that PN does not harbor particularly disease-specific immune activation pathways that are typically found in AD, but is rather characterized by the upregulation of stromal remodeling mechanisms that might directly impact itch fibers.","doi":null,"public_access_enabled":true,"withdrawn":false,"archive":false,"event":"64122c02bf3c20001b66957a","fileid":"ISID2023-ISID0150","event_short_name":"ISID2023","embargoed":true,"organization_id":"6130f6851d09b6db5da0a40f","authors_v2":[{"id":"5d4980cf8fb7e44098e72f59","full_name":"Natalia Alkon","avatar_url":"https://storage.googleapis.com/morressier_avatars_production/e93835c1-7109-4b9e-baa3-b60275c1b276.jpg","author_organization":"Medical University of Vienna","author_organization_id":"5eba80039652df329a982f96","orcid_id":null}],"web_views":48,"web_bookmarks":0,"web_downloads":14,"objectID":"641999d860d56100127c2747","_highlightResult":{"title":{"value":"ISID0150 - Single-cell RNA sequencing defines disease-specific differences between prurigo nodularis and atopic dermatitis","matchLevel":"none","matchedWords":[]},"abstract_id":{"value":"ISID0150","matchLevel":"none","matchedWords":[]},"abstract":{"value":"Prurigo nodularis (PN) is an inflammatory skin disease that is maintained by a chronic itch-scratch cycle likely rooted in neuro-immunological dysregulation with an unknown origin. 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