Islet autoimmunity in infants with a Type I diabetic relative is common but is frequently restricted to one autoantibody.
OBJECTIVE
To determine the sequence of development of islet autoantibodies and their relation to HLA genes in infants at risk for Type I diabetes followed from birth.


METHODS
We followed 357 (189 male, 168 female) infants, with a first degree relative with Type I diabetes for a mean of 3 years from birth. Human leukocyte antigen typing and assays for insulin autoantibodies (IAA), glutamic acid decarboxylase antibodies (GADAb) and tyrosine phosphatase IA2 (IA2Ab) antibodies were done on cord blood, and venous blood was sampled every 6 months for IAA, GADAb and IA2Ab.


RESULTS
We did not find any antibodies in 263 (73%) infants; 50 (14%) were positive for a single antibody once, 19 (5%) for a single antibody more than once and 25 (7%) for two or more antibodies. Of the latter, 10 (2.8% overall) were persistently positive; they had higher frequencies of HLA DR4 (p < 0.01) and HLA DR3, 4 (p < 0.05). Of the group persistently positive for two or more antibodies four infants developed diabetes. Insulin autoantibodies were the first ones to develop in 64% of infants with two or more antibodies.


CONCLUSIONS
Infants with high risk HLA-DR alleles and multiple antibodies at high risk for diabetes were identified. A much larger group of infants had transient low level increases usually of a single antibody. Whereas transient low level positivity could be attributed to difficulties with assay technique and cut off levels for normality, the results overall support the phenomenon of transient 'self limited' islet autoimmunity in at risk infants.
Colman
P G
PG
Department of Diabetes and Endocrinology, The Royal Melbourne Hospital, Victoria, Australia.
Steele
C
C
Couper
J J
JJ
Beresford
S J
SJ
Powell
T
T
Kewming
K
K
Pollard
A
A
Gellert
S
S
Tait
B
B
Honeyman
M
M
Harrison
L C
LC
D000375:Aging / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D005500:Follow-Up Studies; D005968:Glutamate Decarboxylase / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D009679:Nuclear Family; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology
D001323:Autoantibodies; D006684:HLA-DR Antigens; D007328:Insulin; C024211:islet cell antibody; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D005968:Glutamate Decarboxylase