Daha önce biyolojik ajan kullanmamış psöriazis tanılı hastaların biyolojik ajan kullanımı sürecinde serum sitokin (TNF-?,IFN-?2, IFN-?, IL-1ß, IL-6, IL-8, IL-10, IL-12p70, IL-17A,IL-18, IL-23, IL-33, MCP-1) değerlerindeki değişimlerin değerlendirilmesi
Küçük Resim Yok
Tarih
2024
Yazarlar
Dergi Başlığı
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Yayıncı
Tekirdağ Namık Kemal Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Psöriazis, immün aracılı kronik inflamatuar bir deri hastalığıdır. Proinflamatuar sitokinler patogenezde önemli bir role sahiptir. Mevcut tedaviler temel olarak TNF-?, IL-12, IL-17 veya IL-23 yolakları üzerinde etkilidir. Tedavi öncesi sitokin düzeylerinin belirlenmesinin, hastalık aktivitesinin izlenmesi ve kişiselleştirilmiş tedavi seçimi için yararlı biyobelirteçler olarak kullanılabileceği düşünülmektedir. Bu çalışmanın amacı, psöriazis hastalarında hastalık şiddetini, tedavi yanıtını ve hastalık prognozunu tahmin etmeye yardımcı olabilecek biyobelirteçlerin oluşturulmasına katkıda bulunmak ve sağlıklı kontrollerle karşılaştırmaktır. Biyolojik naif 40 psöriazis vulgaris hastası ve 15 sağlıklı bireyde biyolojik ajanlarla tedaviden önce ve tedaviden dört ay sonra sitokinlerin (TNF-?, IFN-?2, IFN-?, IL-1?, IL-6, IL- 8, IL-10, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-33, MCP-1) serum seviyelerindeki değişiklikleri analiz ettik. Sitokin seviyelerinin belirlenmesi için flow sitometri yöntemi (LEGENDplexTM Multi-Analyte Flow Assay Kit Human Inflammation Panel 1, 13 Plex with V-bottom Plate [BioLegend, San Diego, CA]) kullanıldı. PAŞİ (Psöriazis Alan Şiddet İndeksi) ve DYKÖ (Dermatoloji Yaşam Kalitesi Ölçeği) skorları dahil olmak üzere klinik ve demografik bilgiler kaydedildi. Ayrıca, akut faz reaktanları (CRP, ESH, ferritin, albümin) tedaviden önce ve dört ay sonra ölçüldü. Elde edilen veriler NCSS 2007 istatiatik yazılım programı kullanılarak analiz edilmiştir. Tedavinin dördüncü ayındaki PAŞİ ve DYKÖ skorları başlangıca kıyasla anlamlı derecede düşük bulunmuştur (sırasıyla p=0.000, p=0.0001). Sitokin değerleri incelendiğinde; hastaların tedavi sonrası IFN-? seviyelerinde yükselme görüldü (p=0,007). Hastaların tedavi öncesi IL-33 ve IL-1? seviyeleri sağlıklılardan düşük bulundu (p=0,045) fakat tedavi öncesi ve sonrası bu sitokinlerin ortalamaları arasında değişiklik olmadı. Biyolojik ajanlar arasında IL- 17A fark düzeyleri sadece sekukinumab kullanan hastalarda daha yüksek bulundu (p=0.022). Sekukinumab grubunun tedavi öncesi ve sonrası IL-17A farkı diğer ilaçlardan daha yüksekken (p=0.004 p=0.009), diğer biyolojik ajanlar arasında istatistiksel bir fark gözlenmedi (p>0.05). Hastalık başlangıç yaşı, PAŞİ ve DYKÖ ile sitokin seviyeleri arasında korelasyon saptanmadı. Hastaların ESH, CRP ve ferritin değerleri tedavi öncesinde sağlıklı kontrollerden daha yüksekti (sırasıyla p=0.011, p=0.022 ve p=0.037). Ancak, psöriazis hastalarında tedavi sonrasında sadece ESH azaldı (p=0.027). Bu çalışmada serum sitokin düzeylerinde anlamlı bir farklılık bulunmamıştır. Ancak literatür, serum seviyeleri değişmeden kalabilirken, doku seviyelerinin önemli ölçüde farklı olabileceğini göstermektedir. Gelecekteki çalışmalar hem serum hem de doku düzeylerinde sitokin analizlerini içermelidir.
SUMMARY Psoriasis is an immune-mediated chronic inflammatory skin disease. Proinflammatory cytokines have an important role in the pathogenesis. Current treatments mainly act on TNF-?, IL-12, IL-17 or IL-23 pathways. It is thought that determination of cytokine levels before treatment can be used as useful biomarkers for monitoring disease activity and personalized treatment selection. The aim of this study is to contribute to the establishment of biomarkers that can help predict disease severity, treatment response and disease prognosis in patients with psoriasis also compare healthy controls. We analyzed the changes in serum levels of cytokines (TNF-?, IFN-?2, IFN-?, IL-1?, IL-6, IL-8, IL-10, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-23, IL-33, MCP-1) before and four months after treatment with biological agents in 40 bio-naive psoriasis patients and 15 healthy subjects. Flow cytometry method (LEGENDplexTM Multi-Analyte Flow Assay Kit Human Inflammation Panel 1, 13 Plex with V-bottom Plate [BioLegend, San Diego, CA]) was used for the determination of cytokine levels. Clinical and demographic information, including PASI (Psoriasis Area Severity Index) and DQLS (Dermatology Quality of Life Scale) scores were recorded. In addition, acute phase reactants (CRP, ESR, ferritin, albumin) were measured before and after four months of treatment. The data obtained were analyzed using NCSS 2007 software. PASI and DQLS scores at the forth month of treatment were found to be significantly lower compared to the onset (p=0.000 and p=0.0001, respectively). When cytokine values were analyzed; IFN-? levels of the patients increased after treatment (p=0.007). Pre-treatment IL-33 and IL-1? levels of the patients were lower than healthy subjects (p=0.045), but there was no difference between the mean levels of these cytokines before and after treatment. Among the biologic agents, IL-17A levels were found to be lower only in patients using secukinumab (p=0.022). Pre-treatment and post-treatment IL-17A difference of the secukinumab group was higher than the other drugs (p=0.004 p=0.009), while no statistical difference was observed between the other biologic agents (p>0.05). There was no correlation between age at disease onset, PASI and DQLS and cytokine levels. The ESR, CRP, and ferritinn values of the patients were higher than the healthy controls before treatment (p=0.011, p=0.022, and p=0.037, respectively). However, only ESR decreased after treatment in psoriasis patients (p=0.027). In this study, no significant differences were found in serum cytokine levels. However, the literature shows that while serum levels may remain unchanged, tissue levels can be significantly different. Future studies should include cytokine analyses in both serum and tissue levels.
SUMMARY Psoriasis is an immune-mediated chronic inflammatory skin disease. Proinflammatory cytokines have an important role in the pathogenesis. Current treatments mainly act on TNF-?, IL-12, IL-17 or IL-23 pathways. It is thought that determination of cytokine levels before treatment can be used as useful biomarkers for monitoring disease activity and personalized treatment selection. The aim of this study is to contribute to the establishment of biomarkers that can help predict disease severity, treatment response and disease prognosis in patients with psoriasis also compare healthy controls. We analyzed the changes in serum levels of cytokines (TNF-?, IFN-?2, IFN-?, IL-1?, IL-6, IL-8, IL-10, IL-10, IL-12p70, IL-17A, IL-18, IL-23, IL-23, IL-33, MCP-1) before and four months after treatment with biological agents in 40 bio-naive psoriasis patients and 15 healthy subjects. Flow cytometry method (LEGENDplexTM Multi-Analyte Flow Assay Kit Human Inflammation Panel 1, 13 Plex with V-bottom Plate [BioLegend, San Diego, CA]) was used for the determination of cytokine levels. Clinical and demographic information, including PASI (Psoriasis Area Severity Index) and DQLS (Dermatology Quality of Life Scale) scores were recorded. In addition, acute phase reactants (CRP, ESR, ferritin, albumin) were measured before and after four months of treatment. The data obtained were analyzed using NCSS 2007 software. PASI and DQLS scores at the forth month of treatment were found to be significantly lower compared to the onset (p=0.000 and p=0.0001, respectively). When cytokine values were analyzed; IFN-? levels of the patients increased after treatment (p=0.007). Pre-treatment IL-33 and IL-1? levels of the patients were lower than healthy subjects (p=0.045), but there was no difference between the mean levels of these cytokines before and after treatment. Among the biologic agents, IL-17A levels were found to be lower only in patients using secukinumab (p=0.022). Pre-treatment and post-treatment IL-17A difference of the secukinumab group was higher than the other drugs (p=0.004 p=0.009), while no statistical difference was observed between the other biologic agents (p>0.05). There was no correlation between age at disease onset, PASI and DQLS and cytokine levels. The ESR, CRP, and ferritinn values of the patients were higher than the healthy controls before treatment (p=0.011, p=0.022, and p=0.037, respectively). However, only ESR decreased after treatment in psoriasis patients (p=0.027). In this study, no significant differences were found in serum cytokine levels. However, the literature shows that while serum levels may remain unchanged, tissue levels can be significantly different. Future studies should include cytokine analyses in both serum and tissue levels.
Açıklama
Tıp Fakültesi, Deri ve Zührevi Hast. Ana Bilim Dalı
Anahtar Kelimeler
Dermatoloji, Dermatology
