Promene nivoa CD4+CD25high T ćelija i TGFβ1 u različitim stadijumima adultnog Tipa 1 dijabetesa

Stages in T1D: differences in CD25high T cells and TGFβ1

  • Tanja Miličić Medicinski fakultet UB, Klinika za endokrinologiju, dijabetes i bolesti metabolizma UKCS
  • Aleksandra Jotić Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetski Klinički Centar Srbije, Medicinski fakultet Univerzitet u Beogradu
  • Ivanka Marković Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetski Klinički Centar Srbije, Medicinski fakultet Univerzitet u Beogradu
  • Dušan Popadić Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetski Klinički Centar Srbije, Medicinski fakultet Univerzitet u Beogradu
  • Katarina Lalić Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetski Klinički Centar Srbije, Medicinski fakultet Univerzitet u Beogradu
  • Veljko Uskoković Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetski Klinički Centar Srbije, Medicinski fakultet Univerzitet u Beogradu
  • Ljiljana Lukić Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetski Klinički Centar Srbije, Medicinski fakultet Univerzitet u Beogradu
  • Marija Maćešić Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetski Klinički Centar Srbije, Medicinski fakultet Univerzitet u Beogradu
  • Jelena Stanarčić Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetski Klinički Centar Srbije, Medicinski fakultet Univerzitet u Beogradu
  • Milica Stoiljković Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetski Klinički Centar Srbije, Medicinski fakultet Univerzitet u Beogradu
  • Mina Milovančević Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetski Klinički Centar Srbije, Medicinski fakultet Univerzitet u Beogradu
  • Djurdja Rafailović Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetski Klinički Centar Srbije, Medicinski fakultet Univerzitet u Beogradu
  • Aleksandra Božović Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetski Klinički Centar Srbije, Medicinski fakultet Univerzitet u Beogradu
  • Nina Radisavljević Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetski Klinički Centar Srbije, Medicinski fakultet Univerzitet u Beogradu
  • Nebojša Lalić Klinika za endokrinologiju, dijabetes i bolesti metabolizma, Univerzitetski Klinički Centar Srbije, Medicinski fakultet Univerzitet u Beogradu
Ključne reči: CD4 CD25high T ćelije, TGFβ, prvi rođaci pacijenata sa tipom 1 dijabetesa, tip 1 dijabetesa

Sažetak


Prethodne studije su pokazale važnu ulogu poremećaja nivoa T ćelijskih subsetova u različitim stadijumima razvoja tipa 1 dijabetesa (T1D), dok su podaci vezani za CD25high T ćelije i transformišući faktor rasta β1 (transforming growth factor-TGFβ1), koji parcijalno reflektuju T regulatorni odgovor, i dalje kontroverzni. Analizirali smo nivo (a) CD25high T ćelija (b) TGFβ1 kod 17 prvih rođaka pacijenata sa T1D u stadijumu 1 (first-degree relatives of patients with T1D - FDRs1), sa povećanim rizikom za T1D, (GADA+, IA-2+); 34 FDRs u stadijumu 0 (FDRs0) (GADA-, IA-2-); 24 pacijenta sa novootkrivenim T1D u insulin-zavisnom stanju (insulin requiring state-IRS); 10 pacijenata u kliničkoj remisiji (CR); 18 zdravih kontrola (CTR). Nivo CD4+CD25high T ćelija je analiziran metodom dvobojne imunofluorescencije i protočne citometrije, TGFβ1 ELISA, GADA i IA-2 RIA metodom. Nivo CD25high T ćelija u FDRs1 je niži u poređenju sa kontrolama, FDRs0, IRS i CR (p<0.001). Nivo CD25high T ćelija od 1.19%, sa verovatnoćom 0.667, prediktuje povećan rizik za T1D. Nivo TGFβ1 u FDRs1, FDRs0, i oba stanja u T1D, IRS i CR, je niži u poređenju sa kontrolama (p<0.001). U celini, pokazali smo da stadijum 1, povišen rizik za ispoljavanje T1D, karakterišu smanjenja u nivou CD25high T ćelija i TGFβ1, delimično reflektujući oštećen imunoregulatorni odgovor, što bi mogao biti marker rizika za T1D. FDRs sa i bez rizika za T1D i pacijenti sa T1D bez obzira na stanje, su imali snižen TGFβ1, što sugeriše udruženost TGFβ1 sa familijarnim rizikom i kliničkom manifestacijom T1D. Takođe, klinički tok T1D bi mogao biti moduliran na nivou TGFβ1.

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2024/07/04
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