Abstract | Cilj istraživanja: Sistemska skleroza (SSc) je kronična autoimunosna bolest karakterizirana upalom, vaskulopatijom i fibrozom kože i unutarnjih organa. O imunopatologiji bolesti unatoč brojnim istraživanjima i dalje postoje brojne nejasnoće. Citokini imaju značajnu ulogu u procesu vaskulopatije i fibroze. U ovom presječnom kohortnom istraživanju cilj nam je bio utvrditi serumsku razinu citokina IL-17A, IL-22 i TGF-β1 u bolesnika sa sistemskom sklerozom te utvrditi njihovu povezanost u odnosu na klinička obilježja bolesti.
Ispitanici i metode: U istraživanje je uključeno 42 bolesnika sa sistemskom sklerozom i 30 zdravih pojedinaca koji su činili kontrolnu skupinu. Svim ispitanicima koristeći se ELISA metodom izmjerena je koncentracija serumskih razina IL-17, IL-22 i TGF-β. Skupini bolesnika sa SSc uzeti su podatci iz anamneze i medicinske dokumentacije bolesti, učinjena je opsežna laboratorijska analiza krvi, uključujući i SSc-specifična protutijela te detaljni klinički pregled koji je uključivao modificirani Rodnan skin score (mRSS) za procjenu fibroze kože. Svakom bolesniku učinjena je procjena plućnog statusa na temelju plućnih funkcijskih testova i 6.-minutnog testa hoda te kapilaroskopija za procjenu vaskulopatije. Dobiveni podatci su analizirani i uspoređeni među skupinama.
Rezultati: Serumska razina IL-22 bila je statistički značajno povišena u SSc-bolesnika u odnosu na zdrave ispitanike (p =0,02). Koristeći se ROC krivuljom utvrđeno je da bi IL-22 mogao biti prediktor sistemske skleroze (osjetljivost 64,3 %, specifičnost 63,3%). Značajna povezanost nađena je između serumske razine IL-22 i intersticijske bolesti pluća (p=0,007) u SSc-bolesnika. Nije bilo razlike u serumskoj razini TGF-β i IL-17A između SSc-bolesnika i zdrave kontrolne skupine. Analizirajući skupinu SSc- bolesnika povišene razine IL-17A nađene su kod prisutne plućne arterijske hipertenzije, a povišene razine TGF-β kod bolesnika koji nisu liječeni imunosupresivnom terapijom.
Zaključak: Učinjenim istraživanjem nije jasno utvrđena povezanost između razine izmjerenih IL-17A i TGF-β i fibrotskih obilježja bolesti. Razina IL-22 bila je povišena kod SSc-intersticijske bolesti pluća koja je fibrotska manifestacija bolesti, međutim povezanost nije nađena između ostalih obilježja koji govore u prilog uznapredovale fibroze.
Ovi rezultati upućuju na moguće korištenja IL-22 kao biomarkera za dijagnozu intersticijske bolesti pluća u sistemskoj sklerozi. |
Abstract (english) | Objectives: Systemic sclerosis (SSc) is a chronic, autoimmune disease characterized by inflammation, vasculopathy, and fibrosis of the skin and internal organs. Immunological response in SSc is still poorly understood. Cytokines play a significant role in this process leading to vasculopathy and fibrosis. In this cross-sectional study, we aimed to investigate serum levels of IL-17, IL-22, and TGF-β and to determine their correlation to the clinical features of the disease.
Subjects and methods: 42 SSc patients and 30 healthy individuals were included in the research. In all participants, serum levels of IL-17A, IL-22, and TGF-β were examined using the ELISA method. From SSc patients' medical history, data were collected regarding the duration of the disease, type of disease (limited or diffuse), treatment, and organ involvement. For SSc patients, extensive laboratory workup, including SSc-specific autoantibodies, detailed examination, which included modified Rodnan skin score for the assessment of skin fibrosis, pulmonary function tests, 6-minute walk test, and capillaroscopy was performed. The results were analyzed and compared between the groups.
Results: Serum levels of IL-22 were significantly higher in SSc patients compared to healthy individuals (p=0.02). When using the ROC curve, we found IL-22 to be a good predictor of the disease (sensitivity 64.3%, specificity 63.3%). A positive correlation was found between IL-22 sera levels and interstitial lung disease (p=0.007) in SSc patients. Sera IL–17A and TGF-β1 levels did not differ between the groups. In SSc patients, a positive correlation was found between IL-17A levels and pulmonary artery hypertension. TGF-β was found to be elevated in SSc patients who did not receive immunosuppressive therapy.
Conclusion: In our research, no certain association between serum levels of IL-17A, TGF-β, and fibrotic clinical features was established. IL-22 levels were significantly higher in interstitial lung disease, representing only one fibrotic feature of the disease.
These results suggest IL-22 as a potential biomarker in SSc-related interstitial lung disease. |