Diabetes mellitus-related autoantibodies in childhood autoimmune hepatitis.
OBJECTIVE
To determine the frequency and significance of diabetes mellitus (DM)-related autoantibodies in children with autoimmune hepatitis (AIH).


METHODS
Anti-islet cell antibodies (ICA), insulin autoantibodies (IAA), and anti-glutamic acid decarboxylase (GAD65) antibodies were assessed in 28 children (25 female) with AIH before and after 3-9 years of therapy with azathioprine and prednisone.


RESULTS
There was biochemical and clinical remission of AIH activity in 76% of the children after 1 year of immunosuppressive therapy. Positive ICA and IAA were found in 60.7% and 18.5% of the patients, decreasing to 38.5% and 12% after 3-9 years of therapy. Anti-GAD autoantibodies were present in only one patient who had Graves' disease, high ICA titer, and developed type 1 DM after 3 years. After 3-9 years of follow up, all had normal fasting glycemia, glycosylated hemoglobin (HbA1c), and, with a single exception, normal responses to oral glucose tolerance testing. No increase in the frequencies of HLA antigens was observed in ICA- and IAA-positive patients compared to antibody-negative patients or a control population. The majority of the patients with HLA-DRB1*03 or DRB1*04, however, were positive for ICA (7/10), and three of them had IAA. The frequency of high risk HLA DQB1*0302 or DQB1*02 alleles was low and similar to control frequencies, indicating low-risk for DM despite the presence of DM-related autoimmunity markers.


CONCLUSIONS
AIH in childhood is associated with high frequency of ICA and IAA, with less than expected rates of progression to DM. Immunosuppression reduced ICA and IAA frequency and titers.
da Silva
Maria E R
ME
Laboratory of Medical Investigation, São Paulo Medical School, Brazil.
Porta
Gilda
G
Goldberg
Anna C
AC
Bittencourt
Paulo L
PL
Fukui
Rosa T
RT
Correia
Marcia R S
MR
Miura
Irene K
IK
Pugliese
Renata S
RS
Baggio
Vera L
VL
Cançado
Eduardo L R
EL
Kalil
Jorge
J
Santos
Rosa F
RF
Rochal
Dalva M
DM
Wajchenberg
Bernardo L
BL
Ursich
Mileni J M
MJ
Rosenbloom
Arlan L
AL
Golberg
Ana C
AC
D000199:Actins / Q000276:immunology; D000293:Adolescent; D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D001323:Autoantibodies / Q000032:analysis / Q000096:biosynthesis*; D002648:Child; D002675:Child, Preschool; D019389:Cytochrome P-450 CYP2D6 / Q000276:immunology; D003600:Cytosol / Q000276:immunology; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000276:immunology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005968:Glutamate Decarboxylase / Q000276:immunology; D019693:Hepatitis, Autoimmune / Q000150:complications / Q000276:immunology*; D006801:Humans; D007328:Insulin / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology; D007527:Isoenzymes / Q000276:immunology; D008297:Male; D009130:Muscle, Smooth / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar
D000199:Actins; D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D007328:Insulin; D007527:Isoenzymes; D019389:Cytochrome P-450 CYP2D6; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2