{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:20:21Z","timestamp":1790742021183,"version":"4.1.0"},"reference-count":58,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T00:00:00Z","timestamp":1670198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a multifactorial aetiology that involves a strict interplay between genetic factors, immune dysregulation and lifestyle. Familial forms represent around 40% of total HS cases and show an autosomal dominant mode of inheritance of the disease. In this study, we conducted a whole-exome sequence analysis on an Italian family of 4 members encompassing a vertical transmission of HS. Focusing on rare damaging variants, we identified a rare insertion of one nucleotide (c.225dupA:p.A76Sfs*21) in the <jats:italic>DCD<\/jats:italic> gene encoding for the antimicrobial peptide dermcidin (DCD) that was shared by the proband, his affected father and his 11-years old daughter. Since several transcriptome studies have shown a significantly decreased expression of DCD in HS skin, we hypothesised that the identified frameshift insertion was a loss-of-function mutation that might be associated with HS susceptibility in this family. We thus confirmed by mass spectrometry that DCD levels were diminished in the affected members and showed that the antimicrobial activity of a synthetic DCD peptide resulting from the frameshift mutation was impaired. In order to define the consequences related to a decrease in DCD activity, skin microbiome analyses of different body sites were performed by comparing DCD mutant and wild type samples, and results highlighted significant differences between the groins of mutated and wild type groups. Starting from genetic analysis conducted on an HS family, our findings showed, confirming previous transcriptome results, the potential role of the antimicrobial DCD peptide as an actor playing a crucial part in the etio-pathogenesis of HS and in the maintenance of the skin\u2019s physiological microbiome composition; so, we can hypothesise that DCD could be used as a novel target for personalised therapeutic approach.<\/jats:p>","DOI":"10.3389\/fimmu.2022.1060547","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T04:55:10Z","timestamp":1670216110000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["A rare loss-of-function genetic mutation suggest a role of dermcidin deficiency in hidradenitis suppurativa pathogenesis"],"prefix":"10.3389","volume":"13","author":[{"given":"Paola Maura","family":"Tricarico","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Gratton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Andre\u0301 dos","family":"Santos-Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald Rodrigues de","family":"Moura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blendi","family":"Ura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Sommella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Campiglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Del Vecchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Moltrasio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Berti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adamo Pio","family":"D\u2019Adamo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M. A.","family":"Elsherbini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Staudenmaier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Chersi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Boniotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Krismer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Schittek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Crovella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.00068","article-title":"Hidradenitis suppurativa: Current understanding of pathogenic mechanisms and suggestion for treatment algorithm","volume":"7","author":"Seyed Jafari","year":"2020","journal-title":"Front Med (Lausanne)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.17541","article-title":"Invasive proliferative gelatinous mass' of hidradenitis suppurativa contains distinct inflammatory components","volume":"181","author":"Kidacki","year":"2019","journal-title":"Br J Dermatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp1014163","article-title":"Clinical practice. hidradenitis suppurativa","volume":"366","author":"Jemec","year":"2012","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00005.2017","article-title":"Notch signaling in development, tissue homeostasis, and disease","volume":"97","author":"Siebel","year":"2017","journal-title":"Physiol Rev"},{"key":"B5","doi-asserted-by":"publisher","first-page":"4214","DOI":"10.3390\/ijms21124214","article-title":"Pleiotropic role of notch signaling in human skin diseases","volume":"21","author":"Gratton","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00892","article-title":"An integrated approach to unravel hidradenitis suppurativa etiopathogenesis","volume":"10","author":"Tricarico","year":"2019","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2039","DOI":"10.3390\/biomedicines10082039","article-title":"Hidradenitis suppurativa: A perspective on genetic factors involved in the disease","volume":"10","author":"Moltrasio","year":"2022","journal-title":"Biomedicines"},{"key":"B8","doi-asserted-by":"publisher","first-page":"8415","DOI":"10.1038\/s41598-022-11910-5","article-title":"Holistic health record for hidradenitis suppurativa patients","volume":"12","author":"Tricarico","year":"2022","journal-title":"Sci Rep"},{"key":"B9","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/s41572-020-0149-1","article-title":"Hidradenitis suppurativa","volume":"6","author":"Sabat","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14398","article-title":"Yin and yang: A disrupted skin microbiome and an aberrant host immune response in hidradenitis suppurativa","volume":"30","author":"Schell","year":"2021","journal-title":"Exp Dermatol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0216249","article-title":"The skin transcriptome in hidradenitis suppurativa uncovers an antimicrobial and sweat gland gene signature which has distinct overlap with wounded skin","volume":"14","author":"Coates","year":"2019","journal-title":"PloS One"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903907","article-title":"Deficiency of il-22 contributes to a chronic inflammatory disease: Pathogenetic mechanisms in acne inversa","volume":"186","author":"Wolk","year":"2011","journal-title":"J Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.795217","article-title":"Plant antimicrobial peptides as potential tool for topic treatment of hidradenitis suppurativa","volume":"12","author":"Dos Santos-Silva","year":"2021","journal-title":"Front Microbiol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fmedt.2020.610997","article-title":"Mode-of-Action of antimicrobial peptides: Membrane disruption vs. intracellular mechanisms","volume":"2","author":"Benfield","year":"2020","journal-title":"Front Med Technol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"104","DOI":"10.3390\/ijms21010104","article-title":"Expression and function of host defense peptides at inflammation sites","volume":"21","author":"Prasad","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/ced.13959","article-title":"Transcriptome patterns in hidradenitis suppurativa: Support for the role of antimicrobial peptides and interferon pathways in disease pathogenesis","volume":"44","author":"Shanmugam","year":"2019","journal-title":"Clin Exp Dermatol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"13923","DOI":"10.1038\/s41598-017-13600-z","article-title":"Structural basis for the bacterial membrane insertion of dermcidin peptide, dcd-1l","volume":"7","author":"Nguyen","year":"2017","journal-title":"Sci Rep"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.12.8003","article-title":"Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo","volume":"174","author":"Rieg","year":"2005","journal-title":"J Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/ni732","article-title":"Dermcidin: A novel human antibiotic peptide secreted by sweat glands","volume":"2","author":"Schittek","year":"2001","journal-title":"Nat Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2015.07.041","article-title":"Bacteriology of hidradenitis Suppurativa\/Acne inversa: A review","volume":"73","author":"Nikolakis","year":"2015","journal-title":"J Am Acad Dermatol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02965","article-title":"Hidradenitis suppurativa: A systematic review integrating inflammatory pathways into a cohesive pathogenic model","volume":"9","author":"Vossen","year":"2018","journal-title":"Front Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14141","article-title":"A systematic review and critical appraisal of metagenomic and culture studies in hidradenitis suppurativa","volume":"30","author":"Williams","year":"2021","journal-title":"Exp Dermatol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2018.09.036","article-title":"Are bacteria infectious pathogens in hidradenitis suppurativa? debate at the symposium for hidradenitis suppurativa advances meeting, November 2017","volume":"139","author":"Naik","year":"2019","journal-title":"J Invest Dermatol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.jdermsci.2020.05.004","article-title":"Altered keratinization and vitamin d metabolism may be key pathogenetic pathways in syndromic hidradenitis suppurativa: A novel whole exome sequencing approach","volume":"99","author":"Brandao","year":"2020","journal-title":"J Dermatol Sci"},{"key":"B25","doi-asserted-by":"publisher","first-page":"2278","DOI":"10.3390\/ijms23042278","article-title":"Variant enrichment analysis to explore pathways functionality in complex autoinflammatory skin disorders through whole exome sequencing analysis","volume":"23","author":"Brandao","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B26","unstructured":""},{"key":"B27","unstructured":""},{"key":"B28","unstructured":""},{"key":"B29","unstructured":""},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-018-0051-x","article-title":"Strelka2: Fast and accurate calling of germline and somatic variants","volume":"15","author":"Kim","year":"2018","journal-title":"Nat Methods"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603","article-title":"Annovar: Functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi0506s47","article-title":"Comparative protein structure modeling using modeller","volume":"47","author":"Webb","year":"2014","journal-title":"Curr Protoc Bioinf"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-015-7658-1_21","article-title":"Interaction models for water in relation to protein hydration. in: Pullman, b. (Eds) intermolecular forces","volume":"14","author":"Berendsen","year":"1981","journal-title":"Jerusalem Symp Quantum Chem Biochem"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1021\/ct700301q","article-title":"Gromacs 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation","volume":"4","author":"Hess","year":"2008","journal-title":"J Chem Theory Comput"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20090","article-title":"A biomolecular force field based on the free enthalpy of hydration and solvation: The gromos force-field parameter sets 53a5 and 53a6","volume":"25","author":"Oostenbrink","year":"2004","journal-title":"J Comput Chem"},{"key":"B36","doi-asserted-by":"publisher","first-page":"10871","DOI":"10.3390\/ijms221910871","article-title":"Characterization of the human eccrine sweat proteome-a focus on the biological variability of individual sweat protein profiles","volume":"22","author":"Burat","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B37","article-title":"A simple ultraviolet spectrophotometric method for the determination of protein","volume":"48","author":"Waddell","year":"1956","journal-title":"J Lab Clin Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1021\/jf070337l","article-title":"Prediction of molar extinction coefficients of proteins and peptides using uv absorption of the constituent amino acids at 214 nm to enable quantitative reverse phase high-performance liquid chromatography-mass spectrometry analysis","volume":"55","author":"Kuipers","year":"2007","journal-title":"J Agric Food Chem"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnetjournal"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3869","article-title":"Dada2: High-resolution sample inference from illumina amplicon data","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat Methods"},{"key":"B41","unstructured":"R: A language and environment for statistical computing. version 4.0.52021"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0209-9","article-title":"Reproducible, interactive, scalable and extensible microbiome data science using qiime 2","volume":"37","author":"Bolyen","year":"2019","journal-title":"Nat Biotechnol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s40168-020-00841-w","article-title":"Construction of habitat-specific training sets to achieve species-level assignment in 16s rrna gene datasets","volume":"8","author":"Escapa","year":"2020","journal-title":"Microbiome"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061217","article-title":"Phyloseq: An r package for reproducible interactive analysis and graphics of microbiome census data","volume":"8","author":"McMurdie","year":"2013","journal-title":"PloS One"},{"key":"B45","unstructured":""},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for rna-seq data with Deseq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"2039","DOI":"10.3390\/biomedicines10082039","article-title":"Hidradenitis suppurativa: A perspective on genetic factors involved in the disease","volume":"10","author":"Moltrasio","year":"2022","journal-title":"Biomedicines"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2230.2001.00876.x","article-title":"Early-onset hidradenitis suppurativa","volume":"26","author":"Palmer","year":"2001","journal-title":"Clin Exp Dermatol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2014.11.017","article-title":"Correlation of early-onset hidradenitis suppurativa with stronger genetic susceptibility and more widespread involvement","volume":"72","author":"Deckers","year":"2015","journal-title":"J Am Acad Dermatol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0000000000000253","article-title":"Current concepts in the management of hidradenitis suppurativa in children","volume":"27","author":"Danby","year":"2015","journal-title":"Curr Opin Pediatr"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.332270","article-title":"Structure-activity analysis of the dermcidin-derived peptide dcd-1l, an anionic antimicrobial peptide present in human sweat","volume":"287","author":"Paulmann","year":"2012","journal-title":"J Biol Chem"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2014.12.012","article-title":"The secrets of dermcidin action","volume":"305","author":"Burian","year":"2015","journal-title":"Int J Med Microbiol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.960488","article-title":"Innate immunity and microbial dysbiosis in hidradenitis suppurativa - vicious cycle of chronic inflammation","volume":"13","author":"Chopra","year":"2022","journal-title":"Front Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.19461","article-title":"Exploring the human hair follicle microbiome","volume":"184","author":"Lousada","year":"2021","journal-title":"Br J Dermatol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1923-7","article-title":"Improved protein structure prediction using potentials from deep learning","volume":"577","author":"Senior","year":"2020","journal-title":"Nature"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2010.03.005","article-title":"Analyzing protein structure and function using ancestral gene reconstruction","volume":"20","author":"Harms","year":"2010","journal-title":"Curr Opin Struct Biol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1016\/j.jid.2020.02.046","article-title":"The surface microbiome of clinically unaffected skinfolds in hidradenitis suppurativa: A cross-sectional culture-based and 16s rrna gene amplicon sequencing study in 60 patients","volume":"140","author":"Riverain-Gillet","year":"2020","journal-title":"J Invest Dermatol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1001\/jamadermatol.2017.0904","article-title":"The follicular skin microbiome in patients with hidradenitis suppurativa and healthy controls","volume":"153","author":"Ring","year":"2017","journal-title":"JAMA Dermatol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1060547\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T04:55:14Z","timestamp":1670216114000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.1060547\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,5]]},"references-count":58,"alternative-id":["10.3389\/fimmu.2022.1060547"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.1060547","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,5]]},"article-number":"1060547"}}