title: Increased circulating concentrations of mesencephalic astrocyte-derived neurotrophic factor in children with type 1 diabetes.
abstract: Mesencephalic astrocyte-derived neurotrophic factor (MANF) was recently shown to be essential for the survival and proliferation of pancreatic β-cells in mice, where deletion of MANF resulted in diabetes. The current study aimed at determining whether the concentration of circulating MANF is associated with the clinical manifestation of human type 1 diabetes (T1D). MANF expression in T1D or MANF levels in serum have not been previously studied. We developed an enzyme-linked immunosorbent assay (ELISA) for MANF and measured serum MANF concentrations from 186 newly diagnosed children and adolescents and 20 adults with longer-term T1D alongside with age-matched controls. In healthy controls the mean serum MANF concentration was 7.0 ng/ml. High MANF concentrations were found in children 1-9 years of age close to the diagnosis of T1D. The increased MANF concentrations were not associated with diabetes-predictive autoantibodies and autoantibodies against MANF were extremely rare. Patients with conspicuously high MANF serum concentrations had lower C-peptide levels compared to patients with moderate MANF concentrations. Our data indicate that increased MANF concentrations in serum are associated with the clinical manifestation of T1D in children, but the exact mechanism behind the increase remains elusive.
authors.affiliation: Institute of Biotechnology, University of Helsinki, Finland.|Division of Pharmaceutical Biosciences, Centre for Drug Research, University of Helsinki, Finland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Galli
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland.|Research Programs Unit, Diabetes and Obesity, University of Helsinki, Finland.
authors.forename: Taina
authors.initials: T
authors.lastname: Härkönen
authors.affiliation: Institute of Biotechnology, University of Helsinki, Finland.
authors.forename: Markus T
authors.initials: MT
authors.lastname: Sainio
authors.affiliation: Icosagen Ltd., Tartu, Estonia.
authors.forename: Mart
authors.initials: M
authors.lastname: Ustav
authors.affiliation: Icosagen Ltd., Tartu, Estonia.
authors.forename: Urve
authors.initials: U
authors.lastname: Toots
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, University of Helsinki, Finland.
authors.forename: Arto
authors.initials: A
authors.lastname: Urtti
authors.affiliation: Division of Pharmaceutical Biosciences, Centre for Drug Research, University of Helsinki, Finland.
authors.forename: Marjo
authors.initials: M
authors.lastname: Yliperttula
authors.affiliation: Institute of Biotechnology, University of Helsinki, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Lindahl
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Finland.|Research Programs Unit, Diabetes and Obesity, University of Helsinki, Finland.|Folkhälsan Research Center, Helsinki, Finland.
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.affiliation: Institute of Biotechnology, University of Helsinki, Finland.
authors.forename: Mart
authors.initials: M
authors.lastname: Saarma
authors.affiliation: Institute of Biotechnology, University of Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Lindholm
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D002096:C-Peptide / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009414:Nerve Growth Factors / Q000097:blood*; D009474:Neurons / Q000378:metabolism / Q000473:pathology
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; C099695:MANF protein, human; D009414:Nerve Growth Factors