Role of insulin autoantibody affinity as a predictive marker for type 1 diabetes in young children with HLA-conferred disease susceptibility.
BACKGROUND
Insulin autoantibodies (IAA) are early markers of prediabetic autoimmunity. As transient and fluctuating IAA positivity are common among young children, distinguishing non-progressive IAA from destruction-related IAA is essential when preventive measures are considered. We tested whether children progressing rapidly to type 1 diabetes (progressors) are characterized by a higher prediabetic IAA affinity than IAA-positive children remaining unaffected or progressing more slowly to diabetes (non-progressors), and whether IAA affinity increases towards diagnosis.


METHODS
Finnish children with HLA-conferred diabetes susceptibility were observed from birth for diabetes-associated autoantibodies and progression to overt type 1 diabetes. IAA levels and affinities of the first IAA-positive prediabetic samples and samples obtained closest to the diagnosis in 64 progressors were compared with corresponding values in 64 matched IAA-positive non-progressors.


RESULTS
The median age at diagnosis was 3.9 years in progressors and the median follow-up time 7.6 years among unaffected subjects. In the first samples the median IAA affinity was 1.4 x 10(10) L/mol in both groups (p = 0.33), while at the second sampling it was 1.1 x 10(10) L/mol in progressors and 1.2 x 10(10) L/mol in unaffected subjects (p = 0.46). No changes in affinity levels were observed (p = 0.33 and p = 0.84, respectively). IAA titers increased towards diagnosis among progressors (from a median of 13.6 to 20.1 relative units; p = 0.02).


CONCLUSIONS
Among young IAA-positive children with HLA-conferred disease susceptibility IAA affinity failed to distinguish rapid progressors from slowly or non-progressing subjects. In relation to IAA affinity, no maturation of the humoral immune response was observed over time from seroconversion to diagnosis.
Siljander
Heli
H
Hospital for Children and Adolescents and Folkhälsan Research Center, University of Helsinki, 00014 Helsinki, Finland.
Härkönen
Taina
T
Hermann
Robert
R
Simell
Satu
S
Hekkala
Anne
A
Salonsaari
Riikka-Tiina
RT
Simell
Tuula
T
Simell
Olli
O
Ilonen
Jorma
J
Veijola
Riitta
R
Knip
Mikael
M
D000367:Age Factors; D000915:Antibody Affinity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology; D018450:Disease Progression; D004198:Disease Susceptibility; D005387:Finland; D005500:Follow-Up Studies; D005968:Glutamate Decarboxylase / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007223:Infant; D007330:Insulin Antibodies / Q000097:blood / Q000276:immunology*; D016555:Matched-Pair Analysis; D011236:Prediabetic State / Q000097:blood / Q000276:immunology*; D011237:Predictive Value of Tests; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000276:immunology; D012189:Retrospective Studies
D001323:Autoantibodies; D015415:Biomarkers; D006680:HLA Antigens; D007330:Insulin Antibodies; C024211:islet cell antibody; C516862:PTPRN protein, human; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase