Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus
<i>Background and Objectives</i>: 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 microbi...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Online Access: | https://www.mdpi.com/1648-9144/59/11/2022 |
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| author | Karolina A. Englert Grzegorz Dyduch Agata Kłosowicz Magdalena Spałkowska Andrzej Kazimierz Jaworek Kamila Migacz-Gruszka Aleksandra Jarosz-Chudek Santo Raffaele Mercuri Joanna Szpor Gianluigi Mazzoccoli Giovanni Damiani Anna Wojas-Pelc |
| author_facet | Karolina A. Englert Grzegorz Dyduch Agata Kłosowicz Magdalena Spałkowska Andrzej Kazimierz Jaworek Kamila Migacz-Gruszka Aleksandra Jarosz-Chudek Santo Raffaele Mercuri Joanna Szpor Gianluigi Mazzoccoli Giovanni Damiani Anna Wojas-Pelc |
| author_sort | Karolina A. Englert |
| collection | DOAJ |
| description | <i>Background and Objectives</i>: 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. <i>Materials and Methods</i>: We conducted a case–control study comparing CLE patients retrospectively assigned to three subgroups based on 3–6-month Cutaneous LE Disease Area and Severity Index (CLASI) reduction upon treatment with HCQ (I = <40% vs. II <i>=</i> 40–80% vs. III = >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. <i>Results</i>: 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). <i>Conclusions</i>: TLR9 could be envisaged as a possible biomarker to predict HCQ response level and dosage in CLE patients. |
| first_indexed | 2024-03-09T16:36:54Z |
| format | Article |
| id | doaj.art-1e64efd4e2bc4ace94c4a8260f6de639 |
| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-09T16:36:54Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicina |
| spelling | doaj.art-1e64efd4e2bc4ace94c4a8260f6de6392023-11-24T14:55:04ZengMDPI AGMedicina1010-660X1648-91442023-11-015911202210.3390/medicina59112022Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus ErythematosusKarolina A. Englert0Grzegorz Dyduch1Agata Kłosowicz2Magdalena Spałkowska3Andrzej Kazimierz Jaworek4Kamila Migacz-Gruszka5Aleksandra Jarosz-Chudek6Santo Raffaele Mercuri7Joanna Szpor8Gianluigi Mazzoccoli9Giovanni Damiani10Anna Wojas-Pelc11Department of Dermatology, University Hospital in Krakow, 31-501 Kraków, PolandDepartment of Pathomorphology, Jagiellonian University Medical College in Krakow, 33-332 Kraków, PolandDepartment of Dermatology, University Hospital in Krakow, 31-501 Kraków, PolandDepartment of Dermatology, University Hospital in Krakow, 31-501 Kraków, PolandDepartment of Dermatology, University Hospital in Krakow, 31-501 Kraków, PolandDepartment of Dermatology, University Hospital in Krakow, 31-501 Kraków, PolandDepartment of Dermatology, University Hospital in Krakow, 31-501 Kraków, PolandUnit of Dermatology, IRCCS San Raffaele Hospital, 20132 Milan, ItalyDepartment of Pathomorphology, Jagiellonian University Medical College in Krakow, 33-332 Kraków, PolandDivision of Internal Medicine and Chronobiology Laboratory, Department of Medical Sciences, Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, ItalyUnit of Dermatology, IRCCS San Raffaele Hospital, 20132 Milan, ItalyDepartment of Dermatology, University Hospital in Krakow, 31-501 Kraków, Poland<i>Background and Objectives</i>: 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. <i>Materials and Methods</i>: We conducted a case–control study comparing CLE patients retrospectively assigned to three subgroups based on 3–6-month Cutaneous LE Disease Area and Severity Index (CLASI) reduction upon treatment with HCQ (I = <40% vs. II <i>=</i> 40–80% vs. III = >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. <i>Results</i>: 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). <i>Conclusions</i>: TLR9 could be envisaged as a possible biomarker to predict HCQ response level and dosage in CLE patients.https://www.mdpi.com/1648-9144/59/11/2022cutaneous lupus erythematosusdiscoid lupus erythematosus (DLE)subacute cutaneous lupus erythematosus (SCLE)CLASIhydroxychloroquine responseprecision medicine |
| spellingShingle | Karolina A. Englert Grzegorz Dyduch Agata Kłosowicz Magdalena Spałkowska Andrzej Kazimierz Jaworek Kamila Migacz-Gruszka Aleksandra Jarosz-Chudek Santo Raffaele Mercuri Joanna Szpor Gianluigi Mazzoccoli Giovanni Damiani Anna Wojas-Pelc Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus Medicina cutaneous lupus erythematosus discoid lupus erythematosus (DLE) subacute cutaneous lupus erythematosus (SCLE) CLASI hydroxychloroquine response precision medicine |
| title | Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus |
| title_full | Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus |
| title_fullStr | Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus |
| title_full_unstemmed | Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus |
| title_short | Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus |
| title_sort | cutaneous toll like receptor 9 pre defines hydroxychloroquine dosage in patients with both discoid and subacute lupus erythematosus |
| topic | cutaneous lupus erythematosus discoid lupus erythematosus (DLE) subacute cutaneous lupus erythematosus (SCLE) CLASI hydroxychloroquine response precision medicine |
| url | https://www.mdpi.com/1648-9144/59/11/2022 |
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