Beta-cell, thyroid, gastric, adrenal and coeliac autoimmunity and HLA-DQ types in type 1 diabetes.
The autoimmune attack in type 1 diabetes is not only targeted to beta cells. We assessed the prevalence of thyroid peroxidase (aTPO), parietal cell (PCA), antiadrenal (AAA) and endomysial antibodies (EmA-IgA), and of overt autoimmune disease in type 1 diabetes, in relation to gender, age, duration of disease, age at onset, beta-cell antibody status (ICA, GADA, IA2A) and HLA-DQ type. Sera from 399 type 1 diabetic patients (M/F: 188/211; mean age: 26 +/- 16 years; duration: 9 +/- 8 years) were tested for ICA, PCA, AAA and EmA-IgA by indirect immunofluorescence, and for IA2A (tyrosine phosphatase antibodies), GADA (glutamic acid decarboxylase-65 antibodies) and aTPO by radiobinding assays. The prevalence rates were: GADA 70%; IA2A, 44%; ICA, 39%; aTPO, 22%; PCA, 18%; EmA-IgA, 2%; and AAA, 1%. aTPO status was determined by female gender (beta = - 1.15, P = 0.002), age (beta = 0.02, P = 0.01) and GADA + (beta = 1.06, P = 0.02), but not by HLA-DQ type or IA2A status. Dysthyroidism (P < 0.0001) was more frequent in aTPO + subjects. PCA status was determined by age (beta = 0.03, P = 0.002). We also observed an association between PCA + and GADA + (OR = 1.9, P = 0.049), aTPO + (OR = 1.9, P = 0.04) and HLA DQA1*0501-DQB1*0301 status (OR = 2.4, P = 0.045). Iron deficiency anaemia (OR = 3.0, P = 0.003) and pernicious anaemia (OR = 40, P < 0.0001) were more frequent in PCA + subjects. EmA-IgA + was linked to HLA DQA1*0501-DQB1*0201 + (OR = 7.5, P = 0.039), and coeliac disease was found in three patients. No patient had Addison's disease. In conclusion, GADA but not IA2A indicate the presence of thyrogastric autoimmunity in type 1 diabetes. aTPO have a female preponderance, PCA are weakly associated with HLA DQA1*0501-DQB1*0301 and EmA-IgA + with HLA DQA1*0501-DQB1*0201.
De Block
C E
CE
Department of Endocrinology-Diabetology, University of Antwerp, Belgium. cdeblock@uia.ua.ac.be
De Leeuw
I H
IH
Vertommen
J J
JJ
Rooman
R P
RP
Du Caju
M V
MV
Van Campenhout
C M
CM
Weyler
J J
JJ
Winnock
F
F
Van Autreve
J
J
Gorus
F K
FK
D000293:Adolescent; D000311:Adrenal Glands / Q000276:immunology; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D015551:Autoimmunity; D002446:Celiac Disease / Q000276:immunology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005260:Female; D008040:Genetic Linkage; D005968:Glutamate Decarboxylase / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics*; D006801:Humans; D007453:Iodide Peroxidase / Q000276:immunology; D008297:Male; D009928:Organ Specificity; D010295:Parietal Cells, Gastric / Q000276:immunology
D001323:Autoantibodies; D006683:HLA-DQ Antigens; C024211:islet cell antibody; D007453:Iodide Peroxidase; D005968:Glutamate Decarboxylase