Publication: Ankilozan Spondilitin MHC sınıf1 ilişkili immün patogenezin incelenmesi
Abstract
Amaç: Bu çalışmada hastalığın immün mekanizmalarının aydınlatılması için HLA-B27(-) ve HLA-B27(+) hastalarda meydana gelen ankilozan spondilit (AS) patogenezinde hatalı katlanmanın yeri araştırıldı ve sağlıklı kontrollerle farklı parametreler ile karşılaştırılarak hastalık oluşumu ve gelişimi ile ilişkilendirilmesi hedeflendi.Gereç ve yöntem: İç Hastalıkları ABD Romatoloji BD polikliniğine başvuran uluslararası kriterlere göre AS tanısı kesinleşmiş 30 AS hastası ve eş sayıda sağlıklı kontrol çalışmaya dahil edildi. Hasta ve sağlıklı kontrollerden periferik kan örnekleri toplandı. Akış sitometrisi yöntemiyle mononükleer hücrelerinde hatalı katlanma tayini yapıldı, kantitatif PZR ile UPR genleri IRE1, PERK, ATF6 ve XBP1 ekspresyon düzeyleri ve ELISA ile proinflamatuar IL-17, IL-1β, IL-6 ve TNFɑ düzeyleri ölçüldü. Bulgular: XBP1, IRE1 ve PERK gen ekspresyon düzeylerinin hastalar ve sağlıklı kontrollere göre istatistiksel olarak anlamlı bir artış gözlenmezken (p>0.05), ATF6 gen ekspresyon değerleri arasındaki fark istatistiksel olarak anlamlı bulundu (P<0.001). Hastaların serumlarındaki IL-17, IL-1β ve IL-6 düzeylerinde istatiksel olarak anlamlı bir değişim gözlenmedi (p>0.05); fakat AS hastalarının serumlarındaki TNF-α düzeyleri anlamlı bulundu. AS hastalarında HC10 antikoru gözlenmiş olup, hatalı katlanan proteinlerin miktarında sağlıklı kontrollere göre anlamlı bir artış gözlendi.Sonuç: Elde edilen sonuçlar, HLA-B27'nin yanlış katlanması, endoplazmik retikulum (ER) stresine ve katlanmamış protein yanıtının (UPR) aktivasyonuna yol açabileceğini kanıtlar niteliktedir. Bu çalışmanın daha geniş bir hasta popülasyonunu kapsaması hastalığın gelişimi, seyri ve tedavi yanıtları hakkında daha kapsamlı bilgiler sunabilir.
Objective: In this study, we aimed to investigate the role of misfolding in the pathogenesis of ankylosing spondylitis (AS) in both HLA-B27 (-) and HLA-B27 (+) patients to elucidate the immune mechanisms of the disease. The goal was to compare various parameters with healthy controls, aiming to associate them with the development and progression of the disease.Material and methods: 30 patients with confirmed Ankylosing Spondylitis (AS) diagnosis according to international criteria, and 30 healthy controls. Peripheral blood samples were collected from both patients and healthy controls. Misfolding determination was performed on mononuclear cells using the flow cytometry method. The expression levels of Unfolded Protein Response (UPR) genes were quantified using quantitative PCR, and proinflammatory cytokine levels were measured using ELISA.Results: While no statistically significant increase was observed in the expression levels of XBP1, IRE1, and PERK genes in patients compared to healthy controls (p>0.05), the difference in ATF6 gene expression values was found to be statistically significant (P<0.001). There was no statistically significant change in the levels of IL-17, IL-1β, and IL-6 in the patients' sera (p>0.05); however, TNF-α levels in the sera of AS patients were found to be significant. The presence of the HC10 antibody was observed in AS patients, and a significant increase in the amount of misfolded proteins was observed compared to healthy controls.Conclusion: The obtained results suggest that the misfolding of HLA-B27 can lead to endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR). The inclusion of a broader patient population in this study could provide more comprehensive insights into the development, progression, and treatment responses of the disease.
Objective: In this study, we aimed to investigate the role of misfolding in the pathogenesis of ankylosing spondylitis (AS) in both HLA-B27 (-) and HLA-B27 (+) patients to elucidate the immune mechanisms of the disease. The goal was to compare various parameters with healthy controls, aiming to associate them with the development and progression of the disease.Material and methods: 30 patients with confirmed Ankylosing Spondylitis (AS) diagnosis according to international criteria, and 30 healthy controls. Peripheral blood samples were collected from both patients and healthy controls. Misfolding determination was performed on mononuclear cells using the flow cytometry method. The expression levels of Unfolded Protein Response (UPR) genes were quantified using quantitative PCR, and proinflammatory cytokine levels were measured using ELISA.Results: While no statistically significant increase was observed in the expression levels of XBP1, IRE1, and PERK genes in patients compared to healthy controls (p>0.05), the difference in ATF6 gene expression values was found to be statistically significant (P<0.001). There was no statistically significant change in the levels of IL-17, IL-1β, and IL-6 in the patients' sera (p>0.05); however, TNF-α levels in the sera of AS patients were found to be significant. The presence of the HC10 antibody was observed in AS patients, and a significant increase in the amount of misfolded proteins was observed compared to healthy controls.Conclusion: The obtained results suggest that the misfolding of HLA-B27 can lead to endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR). The inclusion of a broader patient population in this study could provide more comprehensive insights into the development, progression, and treatment responses of the disease.
Description
Keywords
Ankilozan spondilit, hatalı protein katlanması, katlanmamış protein yanıtı (UPR) Ankylosing Spondylitis, misfolded protein folding, unfolded protein response (UPR)