{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:06:37Z","timestamp":1789189597899,"version":"build-2803163510"},"reference-count":35,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023331","name":"Leo Pharma","doi-asserted-by":"crossref","award":["22122020"],"award-info":[{"award-number":["22122020"]}],"id":[{"id":"10.13039\/501100023331","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Atopic dermatitis is a common inflammatory skin disease affecting up to 10% of adults. Whether atopic dermatitis exhibits a strong systemic inflammatory signature remains debated. We characterized peripheral whole-blood alterations in adults with moderate-to-severe atopic dermatitis undergoing treatment with dupilumab or baricitinib therapy. Blood samples were collected at weeks 0, 4, and 16. Whole-blood proteins were measured using Olink, transcriptomic profiling was performed by RNA sequencing, and torque teno virus plasma levels were quantified by qPCR. During targeted atopic dermatitis therapy with dupilumab or baricitinib, clustering of samples based on gene expression levels showed no separation by time or treatment, with only a limited number of differentially expressed genes. Proteomic changes were similarly modest; however, treatment was consistently associated with decreased CCL17\/TARC levels. Teno torque virus plasma load remained stable throughout therapy, indicating preserved immunocompetence. These findings suggest that the dominant inflammatory processes in atopic dermatitis may be largely tissue-restricted, supporting the use of peripheral biomarkers for pragmatic monitoring rather than mechanistic discovery.<\/jats:p>","DOI":"10.3390\/ijms27188056","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T10:27:21Z","timestamp":1789036041000},"page":"8056","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peripheral Immune Modulation in Atopic Dermatitis During Dupilumab or Baricitinib Treatment Is Limited, as Assessed by Proteomic, Transcriptomic, and Torque Teno Virus Analyses"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4150-0824","authenticated-orcid":false,"given":"Toke","family":"Touborg","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venereology, Aarhus University Hospital, 8200 Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5857-0626","authenticated-orcid":false,"given":"Anne Sofie","family":"Fr\u00f8lunde","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Aarhus University Hospital, 8200 Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6068-901X","authenticated-orcid":false,"given":"Thomas","family":"Litman","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Copenhagen, 1165 Copenhagen, Denmark"},{"name":"LEO Pharma, 2750 Ballerup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randi","family":"Berg","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1719-3334","authenticated-orcid":false,"given":"Pernille","family":"Koefoed-Nielsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0593-9925","authenticated-orcid":false,"given":"Mette","family":"Deleuran","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Aarhus University Hospital, 8200 Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus","family":"Johansen","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Aarhus University Hospital, 8200 Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Vestergaard","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, Aarhus University Hospital, 8200 Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/S0140-6736(24)02519-4","article-title":"Atopic dermatitis","volume":"405","author":"Brunner","year":"2025","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1111\/bjd.19580","article-title":"The global burden of atopic dermatitis: Lessons from the Global Burden of Disease Study 1990\u20132017","volume":"184","author":"Laughter","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jid.2016.07.012","article-title":"The Burden of Atopic Dermatitis: Summary of a Report for the National Eczema Association","volume":"137","author":"Drucker","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1080\/1744666X.2023.2181790","article-title":"Recent insights into comorbidities in atopic dermatitis","volume":"19","author":"Gewiss","year":"2023","journal-title":"Expert. Rev. Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/j.jaci.2021.01.013","article-title":"Biomarkers in atopic dermatitis\u2014A review on behalf of the International Eczema Council","volume":"147","author":"Thyssen","year":"2021","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1111\/all.70157","article-title":"Large-Scale Blood Proteomic Analysis Across Different Inflammatory Skin Conditions Reveals Extensive Immune Dysregulation with Distinct Biomarker Profiles","volume":"81","author":"Glickman","year":"2025","journal-title":"Allergy"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Gore, E.J., Gard, L., Niesters, H.G.M., and Van Leer Buter, C.C. (2023). Understanding torquetenovirus (TTV) as an immune marker. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1168400"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"110720","DOI":"10.1016\/j.humimm.2023.110720","article-title":"Kinetics of Torque Teno virus in heart transplant patients","volume":"84","author":"Berg","year":"2023","journal-title":"Hum. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Mouton, W., Conrad, A., Bal, A., Boccard, M., Malcus, C., Ducastelle-Lepretre, S., Balsat, M., Barraco, F., Larcher, M.-V., and Fossard, G. (2020). Torque Teno Virus Viral Load as a Marker of Immune Function in Allogeneic Haematopoietic Stem Cell Transplantation Recipients. Viruses, 12.","DOI":"10.3390\/v12111292"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1097\/00002030-200103300-00004","article-title":"Inverse relationship between the titre of TT virus DNA and the CD4 cell count in patients infected with HIV","volume":"15","author":"Shibayama","year":"2001","journal-title":"AIDS"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.cmi.2016.04.007","article-title":"Torquetenovirus: The human virome from bench to bedside","volume":"22","author":"Focosi","year":"2016","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e13778","DOI":"10.1111\/tid.13778","article-title":"Viruses, friends, and foes: The case of Torque Teno Virus and the net state of immunosuppression","volume":"24","author":"Redondo","year":"2022","journal-title":"Transpl. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1056\/NEJMoa1610020","article-title":"Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis","volume":"375","author":"Simpson","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.jaad.2018.01.018","article-title":"Baricitinib in adult patients with moderate-to-severe atopic dermatitis: A phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study","volume":"80","author":"Silverberg","year":"2019","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41423-025-01261-2","article-title":"Type 2 immunity in allergic diseases","volume":"22","author":"Ogulur","year":"2025","journal-title":"Cell. Mol. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Brani, P., Manzoor, H.Z., Spezia, P.G., Vigezzi, A., Ietto, G., Dalla Gasperina, D., Minosse, C., Bosi, A., Giaroni, C., and Carcano, G. (2025). Torque Teno Virus: Lights and Shades. Viruses, 17.","DOI":"10.3390\/v17030334"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"84","DOI":"10.2500\/aap.2019.40.4202","article-title":"Pathophysiology of atopic dermatitis: Clinical implications","volume":"40","author":"Kim","year":"2019","journal-title":"Allergy Asthma Proc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.jaci.2022.02.001","article-title":"Blood transcriptome profiling identifies 2 candidate endotypes of atopic dermatitis","volume":"150","author":"Rodriguez","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3107","DOI":"10.1111\/all.14859","article-title":"Vascular inflammation in moderate-to-severe atopic dermatitis is associated with enhanced Th2 response","volume":"76","author":"Villani","year":"2021","journal-title":"Allergy"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.jaad.2020.05.052","article-title":"The role of thymus and activation-regulated chemokine as a marker of severity of atopic dermatitis","volume":"84","author":"Himadri","year":"2021","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1007\/s13555-025-01481-4","article-title":"Lebrikizumab Rapidly Lowers Inflammatory Biomarkers with Clinical Correlations in Moderate-to-Severe Atopic Dermatitis","volume":"15","author":"Sun","year":"2025","journal-title":"Dermatol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Olydam, J.I., Litman, T., Nijsten, T., Hoof, I., Koopmann, W., Pardo, L.M., and Hijnen, D. (2026). Serum proteomic changes in atopic dermatitis patients treated with cyclosporine. PLoS ONE, 21, Correction in PLoS ONE 2026, 21, e0357330.","DOI":"10.1371\/journal.pone.0357330"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1046\/j.1523-1747.2000.00115.x","article-title":"A Th2 Chemokine, TARC, Produced by Keratinocytes May Recruit CLA+CCR4+ Lymphocytes into Lesional Atopic Dermatitis Skin","volume":"115","author":"Vestergaard","year":"2000","journal-title":"J. Investig. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1016\/j.jaci.2022.11.023","article-title":"Skin TARC\/CCL17 increase precedes the development of childhood atopic dermatitis","volume":"151","author":"Halling","year":"2023","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jaci.2018.08.022","article-title":"Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis","volume":"143","author":"Bissonnette","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1016\/j.jid.2018.12.018","article-title":"Atopic Dermatitis Is an IL-13-Dominant Disease with Greater Molecular Heterogeneity Compared to Psoriasis","volume":"139","author":"Tsoi","year":"2019","journal-title":"J. Investig. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/all.13954","article-title":"Interleukin-13: Targeting an underestimated cytokine in atopic dermatitis","volume":"75","author":"Bieber","year":"2020","journal-title":"Allergy"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Tashiro, T., and Sawada, Y. (2022). Psoriasis and Systemic Inflammatory Disorders. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084457"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1016\/j.jaci.2012.06.044","article-title":"Comparative transcriptomic analyses of atopic dermatitis and psoriasis reveal shared neutrophilic inflammation","volume":"130","author":"Choy","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chen, M., Wen, X., Liu, J., Yang, G., Li, Q., Jiang, Z., Zhang, X., Cai, Z., and Zhang, L. (2025). Recurrence and influencing factors of moderate-to-severe atopic dermatitis after dupilumab withdrawal: A retrospective cohort analysis. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1585368"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/imr.13213","article-title":"Functional heterogeneity of human skin-resident memory T cells in health and disease","volume":"316","author":"Strobl","year":"2023","journal-title":"Immunol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1016\/j.jaad.2026.01.076","article-title":"Beyond T helper 2 cells: Integrating immune, barrier, microbial, and neuroimmune pathways in atopic dermatitis pathogenesis","volume":"94","author":"Zhou","year":"2026","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Tokura, Y., Phadungsaksawasdi, P., Kurihara, K., Fujiyama, T., and Honda, T. (2020). Pathophysiology of Skin Resident Memory T Cells. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.618897"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/s41586-018-0836-1","article-title":"Genomic encoding of transcriptional burst kinetics","volume":"565","author":"Larsson","year":"2019","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.jclinepi.2022.08.016","article-title":"Handling missing data in clinical research","volume":"151","author":"Heymans","year":"2022","journal-title":"J. Clin. Epidemiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8056\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:22:22Z","timestamp":1789186942000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8056"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,10]]},"references-count":35,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27188056"],"URL":"https:\/\/doi.org\/10.3390\/ijms27188056","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,10]]}}}