title: Differences in B7 and CD28 family gene expression in the peripheral blood between newly diagnosed young-onset and adult-onset type 1 diabetes patients.
abstract: 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.
authors.affiliation: Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia; Centre for Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia.
authors.forename: K
authors.initials: K
authors.lastname: Pruul
authors.affiliation: Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia; Centre for Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia.
authors.forename: K
authors.initials: K
authors.lastname: Kisand
authors.affiliation: Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia; Centre for Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia.
authors.forename: K
authors.initials: K
authors.lastname: Alnek
authors.affiliation: Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia; Centre for Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia.
authors.forename: K
authors.initials: K
authors.lastname: Metsküla
authors.affiliation: Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia; Centre for Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia.
authors.forename: K
authors.initials: K
authors.lastname: Reimand
authors.affiliation: Children's Clinic of Tartu University Hospital, N. Lunini 6, Tartu 51014, Estonia; Tallinn Children's Hospital, Tervise 28, Tallinn 13419, Estonia.
authors.forename: K
authors.initials: K
authors.lastname: Heilman
authors.affiliation: Children's Clinic of Tartu University Hospital, N. Lunini 6, Tartu 51014, Estonia; Department of Paediatrics, University of Tartu, N. Lunini 6, Tartu 51014, Estonia.
authors.forename: A
authors.initials: A
authors.lastname: Peet
authors.affiliation: Surgery Clinic, Tartu University Hospital, L. Puusepa 8A, Tartu 51014, Estonia.
authors.forename: K
authors.initials: K
authors.lastname: Varik
authors.affiliation: Surgery Clinic, Tartu University Hospital, L. Puusepa 8A, Tartu 51014, Estonia.
authors.forename: M
authors.initials: M
authors.lastname: Peetsalu
authors.affiliation: Tallinn Children's Hospital, Tervise 28, Tallinn 13419, Estonia.
authors.forename: Ü
authors.initials: Ü
authors.lastname: Einberg
authors.affiliation: Children's Clinic of Tartu University Hospital, N. Lunini 6, Tartu 51014, Estonia; Department of Paediatrics, University of Tartu, N. Lunini 6, Tartu 51014, Estonia.
authors.forename: V
authors.initials: V
authors.lastname: Tillmann
authors.affiliation: Department of Immunology, Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia; Centre for Translational Medicine, University of Tartu, Ravila 19, Tartu 50411, Estonia; Estonian Academy of Sciences, Kohtu 6, Tallinn 10130, Estonia. Electronic address: raivo.uibo@ut.ee.
authors.forename: R
authors.initials: R
authors.lastname: Uibo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D060887:B7 Antigens / Q000097:blood* / Q000235:genetics; D018106:CD28 Antigens / Q000097:blood* / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000175:diagnosis; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D059467:Transcriptome; D055815:Young Adult
chemical_list: D060887:B7 Antigens; D018106:CD28 Antigens
keywords: Adulthood-onset diabetes; Childhood-onset diabetes; Gene expression; Immune synapse; Type 1 diabetes