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Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus
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. T...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673105/ https://www.ncbi.nlm.nih.gov/pubmed/38004071 http://dx.doi.org/10.3390/medicina59112022 |
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author | Englert, Karolina A. Dyduch, Grzegorz Kłosowicz, Agata Spałkowska, Magdalena Jaworek, Andrzej Kazimierz Migacz-Gruszka, Kamila Jarosz-Chudek, Aleksandra Mercuri, Santo Raffaele Szpor, Joanna Mazzoccoli, Gianluigi Damiani, Giovanni Wojas-Pelc, Anna |
author_facet | Englert, Karolina A. Dyduch, Grzegorz Kłosowicz, Agata Spałkowska, Magdalena Jaworek, Andrzej Kazimierz Migacz-Gruszka, Kamila Jarosz-Chudek, Aleksandra Mercuri, Santo Raffaele Szpor, Joanna Mazzoccoli, Gianluigi Damiani, Giovanni Wojas-Pelc, Anna |
author_sort | Englert, Karolina A. |
collection | PubMed |
description | 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–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 = 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. 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. |
format | Online Article Text |
id | pubmed-10673105 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106731052023-11-17 Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus Englert, Karolina A. Dyduch, Grzegorz Kłosowicz, Agata Spałkowska, Magdalena Jaworek, Andrzej Kazimierz Migacz-Gruszka, Kamila Jarosz-Chudek, Aleksandra Mercuri, Santo Raffaele Szpor, Joanna Mazzoccoli, Gianluigi Damiani, Giovanni Wojas-Pelc, Anna Medicina (Kaunas) Article 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–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 = 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. 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. MDPI 2023-11-17 /pmc/articles/PMC10673105/ /pubmed/38004071 http://dx.doi.org/10.3390/medicina59112022 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Englert, Karolina A. Dyduch, Grzegorz Kłosowicz, Agata Spałkowska, Magdalena Jaworek, Andrzej Kazimierz Migacz-Gruszka, Kamila Jarosz-Chudek, Aleksandra Mercuri, Santo Raffaele Szpor, Joanna Mazzoccoli, Gianluigi Damiani, Giovanni Wojas-Pelc, Anna Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus |
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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673105/ https://www.ncbi.nlm.nih.gov/pubmed/38004071 http://dx.doi.org/10.3390/medicina59112022 |
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