Differences in B7 and CD28 family gene expression in the peripheral blood between newly diagnosed young-onset and adult-onset type 1 diabetes patients

• Published in: Molecular and cellular endocrinology 2015-09, Vol.412, p.265-271
• Main Authors: Pruul, K., Kisand, K., Alnek, K., Metsküla, K., Reimand, K., Heilman, K., Peet, A., Varik, K., Peetsalu, M., Einberg, Ü., Tillmann, V., Uibo, R.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Adulthood-onset diabetes; Aged; B7 Antigens - blood; B7 Antigens - genetics; Case-Control Studies; CD28 Antigens - blood; CD28 Antigens - genetics; Child; Child, Preschool; Childhood-onset diabetes; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - diagnosis; Female; Gene Expression; Humans; Immune synapse; Male; Middle Aged; Transcriptome; Type 1 diabetes; Young Adult
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2015.05.012

•The inhibitory CD80-CTLA4 pathway is activated in young-onset T1D.•The stimulatory CD86-CD28 pathway is dominant in adult-onset T1D.•These data emphasize costimulation difference between young and adult onset T1D.•Different mechanisms could lead to loss of immune tolerance in children and adults. Differences in the expression of the genes in the antigen-presenting cells ➀ and in the effector cells ➁ of immune synapse in young- and adult-onset type 1 diabetes (T1D) Type-1 diabetes (T1D) is a heterogeneous autoimmune disease, and there are pathogenetic differences between young- and adult-onset T1D patients. We hypothesized that the expressions of genes involved in costimulatory immune system pathways in peripheral blood are differently regulated in young- and adult-onset T1D. Study group I consisted of 80 children, adolescents, and young adults (age range 1.4−21.4 y; 31 controls and 49 T1D patients). Study group II consisted of 48 adults (age range 22.0−78.4 y; 30 controls and 18 T1D patients). The mRNA expression levels of CD86, CD28, CD25, CD226, CD40, BTLA, GITR, PDCD1, FoxP3, TGF-β, ICOS, sCTLA4, flCTLA4, and CD80 were measured in peripheral blood. Genetic polymorphisms (HLA haplotypes; rs231806, rs231775, and rs3087243 in CTLA4; rs763361 in CD226; and rs706778 in CD25) and T1D-associated autoantibodies were analyzed. In group I, there was significantly lower expression of CD226 in T1D patients than in the controls. In group II, there were significantly higher expression levels of CD86 and TGF-β in T1D patients than in the controls. In the T1D patients in group I, the upregulated CD80 expression correlated with the expression of both CTLA4 splice variants (sCTLA4 and flCTLA4). In contrast, in group II, upregulated CD86 correlated with TGF-β and CD25. In group I, the inhibitory CD80-CTLA4 pathway was activated, whereas, in group II, the activation CD86-CD28 pathway and TGF-β production were activated. These results emphasize the differences between young-onset and adult-onset T1D in the regulation of costimulatory pathways. These differences should be considered when developing novel treatments for T1D.