{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:56:35Z","timestamp":1791561395096,"version":"4.3.4"},"reference-count":30,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:00:00Z","timestamp":1700179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Collegium Medicum Jagiellonian University Grant"},{"name":"\u201c5 \u00d7 1000\u201d voluntary contribution"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Cutaneous lupus erythematosus (CLE) presents clinically heterogeneous manifestations, partially explained by the different expression of Toll-like receptors (TLRs) type 8 and 9, located to endosomal compartments where they are poised to recognize microbial nucleic acids. This disease is empirically treated with hydroxychloroquine (HCQ), which is hallmarked with a safe and effective profile, but induces a slow and sometimes clinically insufficient therapeutic response. Currently, no biomarkers predictive of response are validated or even proposed in the scientific literature. We aimed to evaluate endosomal TLR type 7, 8 and 9 as predictive biomarkers of HCQ efficacy. Materials and Methods: We conducted a case\u2013control study comparing CLE patients retrospectively assigned to three subgroups based on 3\u20136-month Cutaneous LE Disease Area and Severity Index (CLASI) reduction upon treatment with HCQ (I = &lt;40% vs. II = 40\u201380% vs. III = &gt;80%). Before HCQ, lesional skin specimens were collected in untreated CLE and through immunohistochemistry; TLR-7, -8 and -9 expression was evaluated in the epidermis and the lymphocytic infiltrate was evaluated in the dermis. Results: Sixty-six lesional skin biopsies were compared with healthy controls. CLE patients displayed lower epidermal expression of total TLR 8 and 9 as well as infiltrating TLR-8, TLR9 + lymphocytes compared to controls. High HCQ responders differed from low responders for TLR-9 positivity (high vs. low) and for the lymphocytic dermal infiltrate (high vs. low). Conclusions: TLR9 could be envisaged as a possible biomarker to predict HCQ response level and dosage in CLE patients.<\/jats:p>","DOI":"10.3390\/medicina59112022","type":"journal-article","created":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:49:47Z","timestamp":1700182187000},"page":"2022","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus"],"prefix":"10.3390","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9435-1340","authenticated-orcid":false,"given":"Karolina A.","family":"Englert","sequence":"first","affiliation":[{"name":"Department of Dermatology, University Hospital in Krakow, 31-501 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Dyduch","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology, Jagiellonian University Medical College in Krakow, 33-332 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"K\u0142osowicz","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital in Krakow, 31-501 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Spa\u0142kowska","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital in Krakow, 31-501 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej Kazimierz","family":"Jaworek","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital in Krakow, 31-501 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"Migacz-Gruszka","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital in Krakow, 31-501 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Jarosz-Chudek","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital in Krakow, 31-501 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santo Raffaele","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Unit of Dermatology, IRCCS San Raffaele Hospital, 20132 Milan, Italy"},{"name":"Italian Center of Precision Medicine and Chronic Inflammation, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Szpor","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology, Jagiellonian University Medical College in Krakow, 33-332 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3535-7635","authenticated-orcid":false,"given":"Gianluigi","family":"Mazzoccoli","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine and Chronobiology Laboratory, Department of Medical Sciences, Fondazione IRCCS \u201cCasa Sollievo della Sofferenza\u201d, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2390-6505","authenticated-orcid":false,"given":"Giovanni","family":"Damiani","sequence":"additional","affiliation":[{"name":"Unit of Dermatology, IRCCS San Raffaele Hospital, 20132 Milan, Italy"},{"name":"Italian Center of Precision Medicine and Chronic Inflammation, 20122 Milan, Italy"},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Wojas-Pelc","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Hospital in Krakow, 31-501 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s40257-023-00774-8","article-title":"Cutaneous Lupus Erythematosus: An Update on Pathogenesis and Future Therapeutic Directions","volume":"24","author":"Niebel","year":"2023","journal-title":"Am. 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