title: High expression of OX40 (CD134) and 4-1BB (CD137) molecules on CD4(+)CD25(high) cells in children with type 1 diabetes.
abstract: OBJECTIVE
  Despite the rapidly rising incidence of diabetes in children, with the highest rise in children<5 years of age, data on mechanisms that trigger severe beta-cells damage are limited. The aim of the study was to assess the frequency of OX40 (CD134) or 4-1BB (CD137) positive cells in the peripheral blood of children with newly diagnosed type 1 diabetes (T1D) in comparison to healthy controls.
  
  
  METHODS
  The study included 33 children (mean age 7.3 ± 5.4 years) with newly diagnosed T1D and 39 age-matched healthy controls. Separate analysis was performed in children<5 years. Flow cytometric analysis was performed using the following markers: CD4, CD25, CD137, and CD134. Fasting C-peptide level was assessed as well.
  
  
  RESULTS
  The frequency of CD4(+)CD25(high)OX40(+) was higher in T1D children than in controls (median value 3.58% vs. 1.1%, respectively; p=0.003). Moreover, T1D children had higher frequency of CD4(+)CD25(high)4-1BB(+) cells than healthy subjects (median value 5.76% vs. 3.74%, respectively; p=0.037). A significant correlation was noted between the age of diabetic children and the C-peptide level (r=0.54, 95% CI [0.19-0.77], p=0.004). In comparison with age-matched controls, children<5 years had higher frequency of CD4(+)CD25(high)OX40(+) (p=0.004) and CD4(+)CD25(high)4-1BB(+) cells (p=0.079).
  
  
  CONCLUSIONS
  Our study showed higher frequency of both OX40 and 4-1BB positive cells in T1D children in comparison to controls. It seems that observed differences might be more pronounced in children<5 years of age than in older subjects. Further clinical studies are needed to determine the age-related differences in the immune system, in the pathogenesis of T1D.
authors.affiliation: Department of Pediatrics, Medical University of Warsaw, Warsaw, Poland. Electronic address: agnieszka.szypowska@gmail.com.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szypowska
authors.affiliation: Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Stelmaszczyk-Emmel
authors.affiliation: Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Demkow
authors.affiliation: Department of Pediatrics, Endocrinology, Diabetology with Cardiology Division, Medical University of Bialystok, Bialystok, Poland.
authors.forename: Włodzimierz
authors.initials: W
authors.lastname: Luczyński
mesh_terms: D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008297:Male; D011379:Prognosis; D053262:Receptors, OX40 / Q000378:metabolism*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000378:metabolism*
chemical_list: C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D053262:Receptors, OX40; C505716:TNFRSF4 protein, human; C505714:TNFRSF9 protein, human; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
keywords: Childhood diabetes; Diabetes type 1; T regulatory cells