Characterisation of rapid progressors to type 1 diabetes among children with HLA-conferred disease susceptibility

Autor: Paula Vähäsalo, Heli Siljander, Jorma Ilonen, Mikael Knip, Johanna Lempainen, Petra M Pöllänen, Antti-Pekka Laine, Jorma Toppari, Riitta Veijola
Přispěvatelé: HUS Children and Adolescents, Diabetes and Obesity Research Program, Research Programs Unit, Clinicum, Children's Hospital, Lastentautien yksikkö, Mikael Knip / Principal Investigator
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Time Factors
PREDICTION
Endocrinology
Diabetes and Metabolism
CHILDHOOD
Autoimmunity
Polymerase Chain Reaction
Insulin autoantibodies
0302 clinical medicine
Islet cell antibodies
HLA Antigens
Insulin-Secreting Cells
Genotype
Prevalence
Longitudinal Studies
Child
Children
Finland
GENERAL-POPULATION
RISK
education.field_of_study
Glutamate Decarboxylase
3. Good health
HLA
Type 1 diabetes
AUTOANTIBODY APPEARANCE
Child
Preschool
Disease Progression
GAD antibodies
Female
YOUNG-CHILDREN
Adolescent
Population
030209 endocrinology & metabolism
Single-nucleotide polymorphism
Human leukocyte antigen
Polymorphism
Single Nucleotide
03 medical and health sciences
Young Adult
Diabetes mellitus
HLA-DQ Antigens
Internal Medicine
medicine
Humans
Genetic Predisposition to Disease
GENOME-WIDE ASSOCIATION
Seroconversion
education
Autoantibodies
business.industry
Prevention
IA-2 antibodies
Autoantibody
ISLET-CELL ANTIBODIES
Infant
NATURAL-HISTORY
medicine.disease
030104 developmental biology
Diabetes Mellitus
Type 1
3121 General medicine
internal medicine and other clinical medicine
Diabetes-associated autoantibodies
Immunology
business
Zdroj: Diabetologia. 60(7)
ISSN: 1432-0428
Popis: Aims/hypothesis In this study, we aimed to characterise rapid progressors to type 1 diabetes among children recruited from the general population, on the basis of HLA-conferred disease susceptibility. Methods We monitored 7410 HLA-predisposed children participating in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study for the development of beta cell autoimmunity and type 1 diabetes from birth over a median follow-up time of 16.2 years (range 0.9-21.1 years). Islet cell antibodies (ICA) and autoantibodies to insulin (IAA), GAD (GADA) and islet antigen 2 (IA-2A) were assessed as markers of beta cell autoimmunity. Rapid progression was defined as progression to clinical type 1 diabetes within 1.5 years of autoantibody seroconversion. We analysed the association between rapid progression and demographic and autoantibody characteristics as well as genetic markers, including 25 non-HLA SNPs predisposing to type 1 diabetes. Results Altogether, 1550 children (21%) tested positive for at least one diabetes-associated autoantibody in at least two samples, and 248 (16%) of seroconverters progressed to type 1 diabetes by the end of 2015. The median time from seroconversion to diagnosis was 0.51 years in rapid progressors (n = 42, 17%) and 5.4 years in slower progressors. Rapid progression was observed both among young ( 7 years), resulting in a double-peak distribution of seroconversion age. Compared with slower progressors, rapid progressors had a higher frequency of positivity for multiple (>= 2) autoantibodies and had higher titres of ICA, IAA and IA-2A at seroconversion, and there was a higher prevalence of the secretor genotype in the FUT2 gene among those carrying the high-risk HLA genotype. Compared with autoantibody-positive non-progressors, rapid progressors were younger, were more likely to carry the high-risk HLA genotype and a predisposing SNP in the PTPN22 gene, had higher frequency of ICA, IAA, GADA and IA-2A positivity and multipositivity, and had higher titres of all four autoantibodies at seroconversion. Conclusions/interpretation At seroconversion, individuals with rapid progression to type 1 diabetes were characterised by a younger age, higher autoantibody titres, positivity for multiple autoantibodies and higher prevalence of a FUT2 SNP. The double-peak profile for seroconversion age among the rapid progressors demonstrates for the first time that rapid progression may take place not only in young children but also in children in early puberty. Rapid progressors might benefit from careful clinical follow-up and early preventive measures.
Databáze: OpenAIRE
Externí odkaz: