Use of Tape Strips to Detect Immune and Barrier Abnormalities in the Skin of Children With Early-Onset Atopic Dermatitis

IMPORTANCE: Molecular profiling of skin biopsies is the criterion standard for evaluating the cutaneous atopic dermatitis (AD) phenotype. However, skin biopsies are not always feasible in children. A reproducible minimally invasive approach that can track cutaneous disease in pediatric longitudinal...

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Veröffentlicht in:Archives of dermatology (1960) 2019-12, Vol.155 (12), p.1358-1370
Hauptverfasser: Guttman-Yassky, Emma, Diaz, Aisleen, Pavel, Ana B, Fernandes, Marie, Lefferdink, Rachel, Erickson, Taylor, Canter, Talia, Rangel, Stephanie, Peng, Xiangyu, Li, Randall, Estrada, Yeriel, Xu, Hui, Krueger, James G, Paller, Amy S
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container_issue 12
container_start_page 1358
container_title Archives of dermatology (1960)
container_volume 155
creator Guttman-Yassky, Emma
Diaz, Aisleen
Pavel, Ana B
Fernandes, Marie
Lefferdink, Rachel
Erickson, Taylor
Canter, Talia
Rangel, Stephanie
Peng, Xiangyu
Li, Randall
Estrada, Yeriel
Xu, Hui
Krueger, James G
Paller, Amy S
description IMPORTANCE: Molecular profiling of skin biopsies is the criterion standard for evaluating the cutaneous atopic dermatitis (AD) phenotype. However, skin biopsies are not always feasible in children. A reproducible minimally invasive approach that can track cutaneous disease in pediatric longitudinal studies or clinical trials is lacking. OBJECTIVE: To assess a minimally invasive approach using tape strips to identify skin biomarkers that may serve as a surrogate to biomarkers identified using whole-tissue biopsies. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of 51 children younger than 5 years recruited children with moderate to severe AD and children without AD from the dermatology outpatient clinics at a children’s hospital. Sixteen tape strips were serially collected from the nonlesional and lesional skin of 21 children who had AD and were less than 6 months from disease initiation and from the normal skin of 30 children who did not have AD between January 22, 2016, and April 20, 2018. MAIN OUTCOMES AND MEASURES: Gene and protein expression were evaluated using quantitative real-time polymerase chain reaction and immunohistochemistry. RESULTS: A total of 51 children younger than 5 years were included in the study; 21 children had moderate to severe AD with less than 6 months of disease duration, and 30 children did not have AD. Of the 21 children with AD, the mean (SD) age was 1.7 (1.7) years, and most were male (15 [71.4%] and white (15 [71.4%]). Of the 30 children without AD, the mean (SD) age was 1.8 (2.0) years, and most were female (20 [66.7%]) and white (22 [73.3%]). Seventy-seven of 79 evaluated immune and barrier gene products were detected (gene detection rate, 97%) in 70 of 71 tape strips (sample detection rate, 99%), with 53 of 79 markers differentiating between children with lesional and/or nonlesional AD from children without AD. Many cellular markers of T cells (CD3), AD-related dendritic cells (Fc ε RI and OX40 ligand receptors), and key inflammatory (matrix metallopeptidase 12), innate (interleukin 8 [IL-8] and IL-6), helper T cell 2 (TH2; IL-4, IL-13, and chemokines CCL17 and CCL26), and TH17/TH22 (IL-19, IL-36G, and S100A proteins) genes were significantly increased in lesional and nonlesional AD compared with tape strips from normal skin. For example, IL-4 mean (SE) for lesional was −15.2 (0.91) and normal was −19.5 (0.48); P 
doi_str_mv 10.1001/jamadermatol.2019.2983
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However, skin biopsies are not always feasible in children. A reproducible minimally invasive approach that can track cutaneous disease in pediatric longitudinal studies or clinical trials is lacking. OBJECTIVE: To assess a minimally invasive approach using tape strips to identify skin biomarkers that may serve as a surrogate to biomarkers identified using whole-tissue biopsies. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of 51 children younger than 5 years recruited children with moderate to severe AD and children without AD from the dermatology outpatient clinics at a children’s hospital. Sixteen tape strips were serially collected from the nonlesional and lesional skin of 21 children who had AD and were less than 6 months from disease initiation and from the normal skin of 30 children who did not have AD between January 22, 2016, and April 20, 2018. MAIN OUTCOMES AND MEASURES: Gene and protein expression were evaluated using quantitative real-time polymerase chain reaction and immunohistochemistry. RESULTS: A total of 51 children younger than 5 years were included in the study; 21 children had moderate to severe AD with less than 6 months of disease duration, and 30 children did not have AD. Of the 21 children with AD, the mean (SD) age was 1.7 (1.7) years, and most were male (15 [71.4%] and white (15 [71.4%]). Of the 30 children without AD, the mean (SD) age was 1.8 (2.0) years, and most were female (20 [66.7%]) and white (22 [73.3%]). Seventy-seven of 79 evaluated immune and barrier gene products were detected (gene detection rate, 97%) in 70 of 71 tape strips (sample detection rate, 99%), with 53 of 79 markers differentiating between children with lesional and/or nonlesional AD from children without AD. Many cellular markers of T cells (CD3), AD-related dendritic cells (Fc ε RI and OX40 ligand receptors), and key inflammatory (matrix metallopeptidase 12), innate (interleukin 8 [IL-8] and IL-6), helper T cell 2 (TH2; IL-4, IL-13, and chemokines CCL17 and CCL26), and TH17/TH22 (IL-19, IL-36G, and S100A proteins) genes were significantly increased in lesional and nonlesional AD compared with tape strips from normal skin. For example, IL-4 mean (SE) for lesional was −15.2 (0.91) and normal was −19.5 (0.48); P &lt; .001. Parallel decreases occurred in epidermal barrier gene products (FLG, CLDN23, and FA2H) and negative immune regulators (IL-34 and IL-37). For example, the decrease for FLG lesional was mean (SE) −2.9 (0.42) and for normal was 2.2 (0.45); P &lt; .001. Associations were found between disease severity or transepidermal water loss and TH2 (IL-33 and IL-4R) and TH17/TH22 (IL-36G and S100As) products in lesional and nonlesional AD skin (evaluated using the SCORing Atopic Dermatitis, Eczema Area and Severity Index, and Pruritus Atopic Dermatitis Quickscore tools). CONCLUSIONS AND RELEVANCE: In this study, tape strips provide a minimally invasive alternative for serially evaluating AD-associated cutaneous biomarkers and may prove useful for tracking pediatric AD therapeutic response and predicting future course and comorbidities.</description><identifier>ISSN: 2168-6068</identifier><identifier>EISSN: 2168-6084</identifier><identifier>DOI: 10.1001/jamadermatol.2019.2983</identifier><identifier>PMID: 31596431</identifier><language>eng</language><publisher>United States: American Medical Association</publisher><subject>Biopsy ; Children &amp; youth ; Childrens health ; Comments ; Dermatitis ; Eczema ; Online First ; Original Investigation ; Pediatrics</subject><ispartof>Archives of dermatology (1960), 2019-12, Vol.155 (12), p.1358-1370</ispartof><rights>Copyright American Medical Association Dec 2019</rights><rights>Copyright 2019 American Medical Association. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a461t-18645537cd05ff93a53bf790ae31d64f398cf6d8fdf6cc0db9fadb88f3db88673</citedby><cites>FETCH-LOGICAL-a461t-18645537cd05ff93a53bf790ae31d64f398cf6d8fdf6cc0db9fadb88f3db88673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://jamanetwork.com/journals/jamadermatology/articlepdf/10.1001/jamadermatol.2019.2983$$EPDF$$P50$$Gama$$H</linktopdf><linktohtml>$$Uhttps://jamanetwork.com/journals/jamadermatology/fullarticle/10.1001/jamadermatol.2019.2983$$EHTML$$P50$$Gama$$H</linktohtml><link.rule.ids>64,230,314,777,781,882,3327,27905,27906,76238,76241</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31596431$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guttman-Yassky, Emma</creatorcontrib><creatorcontrib>Diaz, Aisleen</creatorcontrib><creatorcontrib>Pavel, Ana B</creatorcontrib><creatorcontrib>Fernandes, Marie</creatorcontrib><creatorcontrib>Lefferdink, Rachel</creatorcontrib><creatorcontrib>Erickson, Taylor</creatorcontrib><creatorcontrib>Canter, Talia</creatorcontrib><creatorcontrib>Rangel, Stephanie</creatorcontrib><creatorcontrib>Peng, Xiangyu</creatorcontrib><creatorcontrib>Li, Randall</creatorcontrib><creatorcontrib>Estrada, Yeriel</creatorcontrib><creatorcontrib>Xu, Hui</creatorcontrib><creatorcontrib>Krueger, James G</creatorcontrib><creatorcontrib>Paller, Amy S</creatorcontrib><title>Use of Tape Strips to Detect Immune and Barrier Abnormalities in the Skin of Children With Early-Onset Atopic Dermatitis</title><title>Archives of dermatology (1960)</title><addtitle>JAMA Dermatol</addtitle><description>IMPORTANCE: Molecular profiling of skin biopsies is the criterion standard for evaluating the cutaneous atopic dermatitis (AD) phenotype. However, skin biopsies are not always feasible in children. A reproducible minimally invasive approach that can track cutaneous disease in pediatric longitudinal studies or clinical trials is lacking. OBJECTIVE: To assess a minimally invasive approach using tape strips to identify skin biomarkers that may serve as a surrogate to biomarkers identified using whole-tissue biopsies. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of 51 children younger than 5 years recruited children with moderate to severe AD and children without AD from the dermatology outpatient clinics at a children’s hospital. Sixteen tape strips were serially collected from the nonlesional and lesional skin of 21 children who had AD and were less than 6 months from disease initiation and from the normal skin of 30 children who did not have AD between January 22, 2016, and April 20, 2018. MAIN OUTCOMES AND MEASURES: Gene and protein expression were evaluated using quantitative real-time polymerase chain reaction and immunohistochemistry. RESULTS: A total of 51 children younger than 5 years were included in the study; 21 children had moderate to severe AD with less than 6 months of disease duration, and 30 children did not have AD. Of the 21 children with AD, the mean (SD) age was 1.7 (1.7) years, and most were male (15 [71.4%] and white (15 [71.4%]). Of the 30 children without AD, the mean (SD) age was 1.8 (2.0) years, and most were female (20 [66.7%]) and white (22 [73.3%]). Seventy-seven of 79 evaluated immune and barrier gene products were detected (gene detection rate, 97%) in 70 of 71 tape strips (sample detection rate, 99%), with 53 of 79 markers differentiating between children with lesional and/or nonlesional AD from children without AD. Many cellular markers of T cells (CD3), AD-related dendritic cells (Fc ε RI and OX40 ligand receptors), and key inflammatory (matrix metallopeptidase 12), innate (interleukin 8 [IL-8] and IL-6), helper T cell 2 (TH2; IL-4, IL-13, and chemokines CCL17 and CCL26), and TH17/TH22 (IL-19, IL-36G, and S100A proteins) genes were significantly increased in lesional and nonlesional AD compared with tape strips from normal skin. For example, IL-4 mean (SE) for lesional was −15.2 (0.91) and normal was −19.5 (0.48); P &lt; .001. Parallel decreases occurred in epidermal barrier gene products (FLG, CLDN23, and FA2H) and negative immune regulators (IL-34 and IL-37). For example, the decrease for FLG lesional was mean (SE) −2.9 (0.42) and for normal was 2.2 (0.45); P &lt; .001. Associations were found between disease severity or transepidermal water loss and TH2 (IL-33 and IL-4R) and TH17/TH22 (IL-36G and S100As) products in lesional and nonlesional AD skin (evaluated using the SCORing Atopic Dermatitis, Eczema Area and Severity Index, and Pruritus Atopic Dermatitis Quickscore tools). CONCLUSIONS AND RELEVANCE: In this study, tape strips provide a minimally invasive alternative for serially evaluating AD-associated cutaneous biomarkers and may prove useful for tracking pediatric AD therapeutic response and predicting future course and comorbidities.</description><subject>Biopsy</subject><subject>Children &amp; youth</subject><subject>Childrens health</subject><subject>Comments</subject><subject>Dermatitis</subject><subject>Eczema</subject><subject>Online First</subject><subject>Original Investigation</subject><subject>Pediatrics</subject><issn>2168-6068</issn><issn>2168-6084</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNpdUUtr3DAYFKWlCWn-QA9B0Esv3uphy_KlsN0maSCQQxJyFLIeXW1tyZXk0vz7ymy6JNFBGvhmRvMxAJxhtMII4S87OUpt4ihzGFYE4W5FOk7fgGOCGa8Y4vXbA2b8CJymtEPlcIRqit-DI4qbjhV4DP7eJwODhXdyMvA2RzclmAP8brJRGV6N4-wNlF7DbzJGZyJc9z6UnweXnUnQeZi3RfirgOKy2bpBR-Phg8tbeC7j8Fjd-GQyXOcwOVV8l9RFmz6Ad1YOyZw-vSfg_uL8bvOjur65vNqsrytZM5wrzFndNLRVGjXWdlQ2tLdth6ShWLPa0o4ryzS32jKlkO47K3XPuaXLzVp6Ar7ufae5H41WxucoBzFFN8r4KIJ04uXEu634Gf4IxhEhjBSDz08GMfyeTcpidEmZYZDehDkJQhElGBFaF-qnV9RdmKMv6xUW4RThFi-J2J6lYkgpGnsIg5FY-hXP-xVLv2LptwjPnq9ykP1vsxA-7glFf5iStiEtRvQfpbquqA</recordid><startdate>20191201</startdate><enddate>20191201</enddate><creator>Guttman-Yassky, Emma</creator><creator>Diaz, Aisleen</creator><creator>Pavel, Ana B</creator><creator>Fernandes, Marie</creator><creator>Lefferdink, Rachel</creator><creator>Erickson, Taylor</creator><creator>Canter, Talia</creator><creator>Rangel, Stephanie</creator><creator>Peng, Xiangyu</creator><creator>Li, Randall</creator><creator>Estrada, Yeriel</creator><creator>Xu, Hui</creator><creator>Krueger, James G</creator><creator>Paller, Amy S</creator><general>American Medical Association</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20191201</creationdate><title>Use of Tape Strips to Detect Immune and Barrier Abnormalities in the Skin of Children With Early-Onset Atopic Dermatitis</title><author>Guttman-Yassky, Emma ; Diaz, Aisleen ; Pavel, Ana B ; Fernandes, Marie ; Lefferdink, Rachel ; Erickson, Taylor ; Canter, Talia ; Rangel, Stephanie ; Peng, Xiangyu ; Li, Randall ; Estrada, Yeriel ; Xu, Hui ; Krueger, James G ; Paller, Amy S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a461t-18645537cd05ff93a53bf790ae31d64f398cf6d8fdf6cc0db9fadb88f3db88673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Biopsy</topic><topic>Children &amp; youth</topic><topic>Childrens health</topic><topic>Comments</topic><topic>Dermatitis</topic><topic>Eczema</topic><topic>Online First</topic><topic>Original Investigation</topic><topic>Pediatrics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guttman-Yassky, Emma</creatorcontrib><creatorcontrib>Diaz, Aisleen</creatorcontrib><creatorcontrib>Pavel, Ana B</creatorcontrib><creatorcontrib>Fernandes, Marie</creatorcontrib><creatorcontrib>Lefferdink, Rachel</creatorcontrib><creatorcontrib>Erickson, Taylor</creatorcontrib><creatorcontrib>Canter, Talia</creatorcontrib><creatorcontrib>Rangel, Stephanie</creatorcontrib><creatorcontrib>Peng, Xiangyu</creatorcontrib><creatorcontrib>Li, Randall</creatorcontrib><creatorcontrib>Estrada, Yeriel</creatorcontrib><creatorcontrib>Xu, Hui</creatorcontrib><creatorcontrib>Krueger, James G</creatorcontrib><creatorcontrib>Paller, Amy S</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Archives of dermatology (1960)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guttman-Yassky, Emma</au><au>Diaz, Aisleen</au><au>Pavel, Ana B</au><au>Fernandes, Marie</au><au>Lefferdink, Rachel</au><au>Erickson, Taylor</au><au>Canter, Talia</au><au>Rangel, Stephanie</au><au>Peng, Xiangyu</au><au>Li, Randall</au><au>Estrada, Yeriel</au><au>Xu, Hui</au><au>Krueger, James G</au><au>Paller, Amy S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Use of Tape Strips to Detect Immune and Barrier Abnormalities in the Skin of Children With Early-Onset Atopic Dermatitis</atitle><jtitle>Archives of dermatology (1960)</jtitle><addtitle>JAMA Dermatol</addtitle><date>2019-12-01</date><risdate>2019</risdate><volume>155</volume><issue>12</issue><spage>1358</spage><epage>1370</epage><pages>1358-1370</pages><issn>2168-6068</issn><eissn>2168-6084</eissn><abstract>IMPORTANCE: Molecular profiling of skin biopsies is the criterion standard for evaluating the cutaneous atopic dermatitis (AD) phenotype. However, skin biopsies are not always feasible in children. A reproducible minimally invasive approach that can track cutaneous disease in pediatric longitudinal studies or clinical trials is lacking. OBJECTIVE: To assess a minimally invasive approach using tape strips to identify skin biomarkers that may serve as a surrogate to biomarkers identified using whole-tissue biopsies. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study of 51 children younger than 5 years recruited children with moderate to severe AD and children without AD from the dermatology outpatient clinics at a children’s hospital. Sixteen tape strips were serially collected from the nonlesional and lesional skin of 21 children who had AD and were less than 6 months from disease initiation and from the normal skin of 30 children who did not have AD between January 22, 2016, and April 20, 2018. MAIN OUTCOMES AND MEASURES: Gene and protein expression were evaluated using quantitative real-time polymerase chain reaction and immunohistochemistry. RESULTS: A total of 51 children younger than 5 years were included in the study; 21 children had moderate to severe AD with less than 6 months of disease duration, and 30 children did not have AD. Of the 21 children with AD, the mean (SD) age was 1.7 (1.7) years, and most were male (15 [71.4%] and white (15 [71.4%]). Of the 30 children without AD, the mean (SD) age was 1.8 (2.0) years, and most were female (20 [66.7%]) and white (22 [73.3%]). Seventy-seven of 79 evaluated immune and barrier gene products were detected (gene detection rate, 97%) in 70 of 71 tape strips (sample detection rate, 99%), with 53 of 79 markers differentiating between children with lesional and/or nonlesional AD from children without AD. Many cellular markers of T cells (CD3), AD-related dendritic cells (Fc ε RI and OX40 ligand receptors), and key inflammatory (matrix metallopeptidase 12), innate (interleukin 8 [IL-8] and IL-6), helper T cell 2 (TH2; IL-4, IL-13, and chemokines CCL17 and CCL26), and TH17/TH22 (IL-19, IL-36G, and S100A proteins) genes were significantly increased in lesional and nonlesional AD compared with tape strips from normal skin. For example, IL-4 mean (SE) for lesional was −15.2 (0.91) and normal was −19.5 (0.48); P &lt; .001. Parallel decreases occurred in epidermal barrier gene products (FLG, CLDN23, and FA2H) and negative immune regulators (IL-34 and IL-37). For example, the decrease for FLG lesional was mean (SE) −2.9 (0.42) and for normal was 2.2 (0.45); P &lt; .001. Associations were found between disease severity or transepidermal water loss and TH2 (IL-33 and IL-4R) and TH17/TH22 (IL-36G and S100As) products in lesional and nonlesional AD skin (evaluated using the SCORing Atopic Dermatitis, Eczema Area and Severity Index, and Pruritus Atopic Dermatitis Quickscore tools). CONCLUSIONS AND RELEVANCE: In this study, tape strips provide a minimally invasive alternative for serially evaluating AD-associated cutaneous biomarkers and may prove useful for tracking pediatric AD therapeutic response and predicting future course and comorbidities.</abstract><cop>United States</cop><pub>American Medical Association</pub><pmid>31596431</pmid><doi>10.1001/jamadermatol.2019.2983</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record>
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subjects Biopsy
Children & youth
Childrens health
Comments
Dermatitis
Eczema
Online First
Original Investigation
Pediatrics
title Use of Tape Strips to Detect Immune and Barrier Abnormalities in the Skin of Children With Early-Onset Atopic Dermatitis
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