Antibodies to the Mr 64,000 (64K) protein in islet cell antibody positive non-diabetic individuals indicate high risk for impaired Beta-cell function

A prospective study of a normal childhood population identified 44
islet cell antibody positive individuals. These subjects were typed
for HLA DR and DQ alleles and investigated for the presence of
antibodies to the Mr 64,000 (64K) islet cell antigen,
complement-fixing islet cell antibodies and radiobinding insulin
autoantibodies to determine their potency in detecting subjects
with impaired Beta-cell function. At initial testing 64K antibodies
were found in six of 44 islet cell antibody positive subjects
(13.6%). The same sera were also positive for complement-fixing
islet cell antibodies and five of them had insulin autoantibodies.
During the follow-up at 18 months, islet cell antibodies remained
detectable in 50% of the subjects studied. In all six cases who
were originally positive, 64K antibodies were persistently
detectable, whereas complement-fixing islet cell antibodies became
negative in two of six and insulin autoantibodies in one of five
individuals. HLA DR4 (p < 0.005) and absence of asparic acid
(Asp) at position 57 of the HLA DQ chain (p < 0.05) were
significantly increased in subjects with 64K antibodies compared
with control subjects. Of 40 individuals tested in the intravenous
glucose tolerance test, three had a first phase insulin response
below the first percentile of normal control subjects. Two children
developed Type 1 (insulin-dependent) diabetes mellitus after 18 and
26 months, respectively. Each of these subjects was non-Asp
homozygous and had persistent islet cell and 64K antibodies. We
conclude that 64K antibodies, complement-fixing islet cell
antibodies and insulin autoantibodies represent sensitive
serological markers in assessing high risk for a progression to
Type 1 diabetes in islet cell antibody positive non-diabetic
individuals.