{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:15:49Z","timestamp":1790270149025,"version":"4.1.0"},"reference-count":87,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:00:00Z","timestamp":1722211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients with recessive dystrophic epidermolysis bullosa (RDEB) experience numerous complications, which are exacerbated by inflammatory dysregulation and infection. Understanding the immunological mechanisms is crucial for selecting medications that balance inflammation control and immunocompetence. In this cross\u2010sectional study, aiming to identify potential immunotherapeutic targets and inflammatory biomarkers, we delved into the interrelationship between clinical severity and systemic inflammatory parameters in a representative RDEB cohort. Encompassing 84 patients aged 1\u201367 and spanning all three Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) severity categories, we analysed the interrelationship of infection history, standard inflammatory markers, systemic cytokines and Ig levels to elucidate their roles in RDEB pathophysiology. Our findings identify C\u2010reactive protein as an excellent biomarker for disease severity in RDEB. A type 2 inflammatory profile prevails among moderate and severe RDEB patients, correlating with dysregulated circulating IgA and IgG. These results underscore the IL4\/IL13 pathways as potential evidence\u2010based therapeutic targets. Moreover, the complete inflammatory scenario aligns with <jats:italic>Staphylococcus aureus<\/jats:italic> virulence mechanisms. Concurrently, abnormalities in IgG, IgE and IgM levels suggest an immunodeficiency state in a substantial number of the cohort's patients. Our results provide new insights into the interplay of infection and immunological factors in the pathogenesis of RDEB.<\/jats:p>","DOI":"10.1111\/exd.15146","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T05:50:26Z","timestamp":1722318626000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Unveiling the value of C\u2010reactive protein as a severity biomarker and the <scp>IL4<\/scp>\/<scp>IL13<\/scp> pathway as a therapeutic target in recessive dystrophic epidermolysis bullosa: A multiparametric cross\u2010sectional study"],"prefix":"10.1111","volume":"33","author":[{"given":"Luc\u00eda","family":"Quintana\u2010Castanedo","sequence":"first","affiliation":[{"name":"Department of Dermatology, IdiPAZ Health Research Institute Hospital La Paz  Madrid Spain"},{"name":"Department of Dermatology Marqu\u00e9s de Valdecilla University Hospital  Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"S\u00e1nchez\u2010Ram\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Immunology, IML and IdISSC Health Research Institute Hospital Cl\u00ednico San Carlos  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"Maseda","sequence":"additional","affiliation":[{"name":"Department of Dermatology, IdiPAZ Health Research Institute Hospital La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Illera","sequence":"additional","affiliation":[{"name":"Departamento de Bioingenier\u00eda Universidad Carlos III de Madrid  Madrid Spain"},{"name":"Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas  Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)\u2010ISCIII  Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS\u2010FJD, UAM)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"P\u00e9rez\u2010Conde","sequence":"additional","affiliation":[{"name":"Department of Dermatology, IdiPAZ Health Research Institute Hospital La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Molero\u2010Luis","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Hospital La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Butta","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hemotherapy, IdiPAZ Health Research Institute Hospital La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena G.","family":"Arias\u2010Salgado","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hemotherapy, IdiPAZ Health Research Institute Hospital La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Monz\u00f3n\u2010Manzano","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hemotherapy, IdiPAZ Health Research Institute Hospital La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Zuluaga","sequence":"additional","affiliation":[{"name":"Department of Statistics and Operations Research Faculty of Medicine  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Mart\u00ednez\u2010Santamar\u00eda","sequence":"additional","affiliation":[{"name":"Departamento de Bioingenier\u00eda Universidad Carlos III de Madrid  Madrid Spain"},{"name":"Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas  Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)\u2010ISCIII  Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS\u2010FJD, UAM)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Fern\u00e1ndez\u2010Arquero","sequence":"additional","affiliation":[{"name":"Department of Immunology, IML and IdISSC Health Research Institute Hospital Cl\u00ednico San Carlos  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara G.","family":"Llames","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)\u2010ISCIII  Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS\u2010FJD, UAM)  Madrid Spain"},{"name":"Unidad de Ingenier\u00eda Tisular Centro Comunitario Sangre y Tejidos de Asturias (CCST)  Oviedo Spain"},{"name":"Instituto Universitario Fern\u00e1ndez\u2010Vega, Fundaci\u00f3n de Investigaci\u00f3n Oftalmol\u00f3gica (FIO)  Oviedo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1lvaro","family":"Meana","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)\u2010ISCIII  Madrid Spain"},{"name":"Unidad de Ingenier\u00eda Tisular Centro Comunitario Sangre y Tejidos de Asturias (CCST)  Oviedo Spain"},{"name":"Instituto Universitario Fern\u00e1ndez\u2010Vega, Fundaci\u00f3n de Investigaci\u00f3n Oftalmol\u00f3gica (FIO)  Oviedo Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)  Oviedo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal","family":"de Lucas","sequence":"additional","affiliation":[{"name":"Department of Dermatology, IdiPAZ Health Research Institute Hospital La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"del R\u00edo","sequence":"additional","affiliation":[{"name":"Departamento de Bioingenier\u00eda Universidad Carlos III de Madrid  Madrid Spain"},{"name":"Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas  Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)\u2010ISCIII  Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS\u2010FJD, UAM)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngeles","family":"Vicente","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Medicine UCM, Health Research Institute of the Hospital Cl\u00ednico San Carlos (IdISSC)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Esc\u00e1mez","sequence":"additional","affiliation":[{"name":"Departamento de Bioingenier\u00eda Universidad Carlos III de Madrid  Madrid Spain"},{"name":"Centro de Investigaciones Energ\u00e9ticas, Medioambientales y Tecnol\u00f3gicas  Madrid Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)\u2010ISCIII  Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Fundaci\u00f3n Jim\u00e9nez D\u00edaz (IIS\u2010FJD, UAM)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Saced\u00f3n","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Faculty of Medicine UCM, Health Research Institute of the Hospital Cl\u00ednico San Carlos (IdISSC)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-0210-0"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.737272"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.18104"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/pde.15239"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-101320-125839"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cia2.12230"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2014.500"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.det.2010.01.010"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.18475"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15051159"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2017.11.010"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.5582\/irdr.2017.01005"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000001528"},{"issue":"4","key":"e_1_2_10_15_1","first-page":"340","article-title":"IL\u20106\/IL\u201010 ratio as a prognostic and predictive marker of the severity of inherited epidermolysis bullosa","volume":"14","author":"Tampoia M","year":"2017","journal-title":"Iranian J Immunol"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17101625"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2017.07.002"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14411"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.15040"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.19898"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-132"},{"issue":"7","key":"e_1_2_10_22_1","first-page":"2584","article-title":"Natural occurrence of autoantibodies against basement membrane proteins in epidermolysis bullosa","volume":"142","author":"Gosty\u0144ski A","year":"2021","journal-title":"J Invest Dermatol"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2013.475"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.945176"},{"issue":"104","key":"e_1_2_10_25_1","first-page":"621","article-title":"Premature death and inherited epidermolysis bullosa (EB): cumulative risk, as assessed by lifetable analysis of the national EB registry dataset","volume":"4","author":"Fine JD","year":"1995","journal-title":"J Invest Dermatol"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.det.2010.01.004"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0000000000003871"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01668"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.18921"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2013.09.041"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.10.080010"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.12751"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.02126"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.630430"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.866379"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11071771"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.5RI0218-084R"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxaa078"},{"issue":"5","key":"e_1_2_10_39_1","first-page":"101","article-title":"The role of IL\u20106 in skin fibrosis and cutaneous wound healing","volume":"8","author":"Johnson BZ","year":"2020","journal-title":"Biomedicine"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2017.83"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.45"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(21)00103-X"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.02.062"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9113741"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-019-01972-3"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.14318"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8332913"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20174070"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2021.03.010"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/dth.15924"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.15432"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/pde.14909"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/dth.15130"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.16729"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdcr.2021.07.036"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.18855"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/pde.14493"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00746-9"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2622"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18051033"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13671-018-0235-8"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.984016"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.594735"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060285"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12617"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2017.01.004"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3346"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/pde.14444"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/pde.13331"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2022.01.020"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajd.13274"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-008-0602-7"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1186\/2047-2994-3-14"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23137482"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2019.05.003"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2017.11.008"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-481X.2006.00159.x"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2015.05.008"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2021.05.023"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(21)00056-9"},{"issue":"2","key":"e_1_2_10_81_1","article-title":"The role of blood viscosity in infectious diseases","volume":"12","author":"Sloop GD","year":"2020","journal-title":"Cureus"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2012.347"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2021.06.005"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/2767012"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2022.07.013"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14062"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1709111115"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-017-0465-8"}],"container-title":["Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.15146","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T15:48:10Z","timestamp":1746632890000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/exd.15146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,29]]},"references-count":87,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1111\/exd.15146"],"URL":"https:\/\/doi.org\/10.1111\/exd.15146","archive":["Portico"],"relation":{},"ISSN":["0906-6705","1600-0625"],"issn-type":[{"value":"0906-6705","type":"print"},{"value":"1600-0625","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,29]]},"assertion":[{"value":"2024-03-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15146"}}