Histopathological and molecular analysis in dermis and epidermis of patients with systemic and localized scleroderma

Objective: Scleroderma has a wide range of clinical manifestations due to vasculopathy, autoimmunity, altered endothelium function, and abnormal fibrosis which are accused in the pathogenesis of the disease. The aim of this study is to shed light on the pathogenesis of the disease in the childhood via dermal immunohistochemical analysis of the cases.
Methods: A single-blind clinical trial is conducted with evaluation of the tissue samples obtained from patients. The samples are stained with PAS, hematoxylin and eosin, E-Cadherin, Connective tissue growth factor (CTGF), Tunnel, and staining for Transforming growth factor beta 1 (TGF-β1) and evaluated by light microscopy. In addition both TGF-β1 level and mRNA expression analyses in plasma and tissue samples from patients are performed. A total of 15 patients (systemic, n = 8 or localized; n = 7) were enrolled in the study.
Results: The mean age of onset of the disease was 9.2±1.2 years, and the mean age of diagnosis was 15.3±3.2 years. Antinuclear antibody (ANA) titer was between 1/160-1/640 in all patients with systemic sclerosis. There was no ANA positivity in patients with localized scleroderma. A total of 22 tissue samples (15 diseased tissues, 7 healthy tissues) were examined. Histopathological examination has shown that two clinically different subgroups have different characteristics at the tissue level.
Conclusions: TGF-β1 levels, which is playing a fundamental role in the pathogenesis of the disease are found in both plasma and skin have been shown high. This elevation was found particularly in patients with systemic scleroderma to be more pronounced. Also in patients with localized scleroderma, skin fibroblasts has been shown to limit the pathologic response.

Sistemik ve lokalize skleroderma hastalarýnda dermis ve epidermisin histopatolojik ve moleküler analizi

Amaç: Skleroderma, hastalýðýn patogenezinde suçlanan vaskülopati, otoimmünite, bozulmuþ endotel fonksiyonu ve anormal fibrozis nedeniyle geniþ bir klinik tabloya sahiptir. Bu çalýþmanýn amacý olgularýn dermal immünohistokimyasal analizi ile çocukluk çaðýnda hastalýðýn patogenezine ýþýk tutmaktýr.
Method: Hastalardan alýnan doku örneklerinin deðerlendirilmesiyle tek kör bir klinik çalýþma yürütüldü. Örnekler PAS, hematoksilen - eozin, E-Cadherin, bað dokusu büyüme faktörü (CTGF), Tunnel ile boyandý ve Transforming growth faktör beta 1 (TGF-β1) boyamasý yapýldý. Iþýk mikroskobu ile deðerlendirildi. Ayrýca hastalardan alýnan plazma ve doku örneklerinde hem TGF-β1 düzeyi hem de mRNA ekspresyon analizleri yapýldý. Çalýþmaya toplam 15 hasta (sistemik, n=8 ve localize, n=7) dahil edildi.
Bulgular: Hastalýðýn ortalama baþlangýç yaþý 9.2±1.2 yýl, ortalama taný yaþý ise 15.3±3.2 yýldý. Sistemik sklerozlu hastalarýn tamamýnda anti nükleer antikor (ANA) titresi 1/160-1/640 arasýnda idi. Lokalize sklerodermalý hastalarda ANA pozitifliði yoktu. Toplam 22 doku örneði (15 hastalýklý doku, 7 saðlýklý doku) incelendi. Histopatolojik incelemede, klinik olarak farklý iki alt grubun doku düzeyinde de farklý özelliklere sahip olduðu gösterilmiþtir.
Sonuç: Hastalýðýn patogenezinde temel rol oynayan TGF-β1 düzeylerinin hem plazmada hem de deride yüksek olduðu gösterilmiþtir. Bu yükselmenin özellikle sistemik sklerodermalý hastalarda daha belirgin olduðu görüldü. Ayrýca lokalize sklerodermalý hastalarda deri fibroblastlarýnýn patolojik yanýtý sýnýrladýðý gösterilmiþtir. (NCI-2023-11-11)