Abstract
Insulin, glutamate decarboxylase (GAD) and the protein tyrosine phosphatase-like molecule IA-2 are major targets of humoral autoimmunity in insulin-dependent diabetes mellitus (IDDM). These autoantibodies are heterogeneous with respect to age and patient human leukocyte antigen (HLA) phenotype. We have previously demonstrated that GAD and IA-2 antibodies potentially identify different subsets of IDDM patients. The aim of this study was to determine whether GAD and IA-2 autoantibodies were associated with different HLA DR phenotypes. We studied 160 patients with IDDM onset before age 16 years. At disease onset serum was tested for GAD and IA-2 antibodies by immunoprecipitation of in vitro-translated 35S-methionine labelled recombinant proteins. IA-2 antibodies were significantly associated with HLA DR4: 67 (86%) of 78 patients with HLA DR4 vs 31 (38%) of 82 non-DR4 patients had IA-2 antibodies (p(c) <0.0001) and IA-2 antibody levels were higher in patients with HLA DR4 (p(c) <0.0001). In contrast, GAD antibodies were more prevalent (p(c) <0.05) and antibody levels highest (p(c) <0.01) inpatients with HLA DR3 phenotypes. These data provide further evidence that, in IDDM, production and titre of major autoantibody specificities are associated with HLA class II alleles.
| Original language | English |
|---|---|
| Pages (from-to) | 1223-1226 |
| Number of pages | 4 |
| Journal | Diabetologia |
| Volume | 39 |
| Issue number | 10 |
| Publication status | Published - 1996 |
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Keywords
- Autoantibodies
- Glutamic acid decarboxylase
- HLA
- IA-2
- Insulin-dependent diabetes mellitus
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Internal Medicine
Cite this
Association of IA-2 autoantibodies with HLA DR4 phenotypes in IDDM. / Genovese, S.; Bonfanti, R.; Bazzigaluppi, E.; Lampasona, V.; Benazzi, E.; Bosi, E.; Chiumello, G.; Bonifacio, E.
In: Diabetologia, Vol. 39, No. 10, 1996, p. 1223-1226.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Association of IA-2 autoantibodies with HLA DR4 phenotypes in IDDM
AU - Genovese, S.
AU - Bonfanti, R.
AU - Bazzigaluppi, E.
AU - Lampasona, V.
AU - Benazzi, E.
AU - Bosi, E.
AU - Chiumello, G.
AU - Bonifacio, E.
PY - 1996
Y1 - 1996
N2 - Insulin, glutamate decarboxylase (GAD) and the protein tyrosine phosphatase-like molecule IA-2 are major targets of humoral autoimmunity in insulin-dependent diabetes mellitus (IDDM). These autoantibodies are heterogeneous with respect to age and patient human leukocyte antigen (HLA) phenotype. We have previously demonstrated that GAD and IA-2 antibodies potentially identify different subsets of IDDM patients. The aim of this study was to determine whether GAD and IA-2 autoantibodies were associated with different HLA DR phenotypes. We studied 160 patients with IDDM onset before age 16 years. At disease onset serum was tested for GAD and IA-2 antibodies by immunoprecipitation of in vitro-translated 35S-methionine labelled recombinant proteins. IA-2 antibodies were significantly associated with HLA DR4: 67 (86%) of 78 patients with HLA DR4 vs 31 (38%) of 82 non-DR4 patients had IA-2 antibodies (p(c) <0.0001) and IA-2 antibody levels were higher in patients with HLA DR4 (p(c) <0.0001). In contrast, GAD antibodies were more prevalent (p(c) <0.05) and antibody levels highest (p(c) <0.01) inpatients with HLA DR3 phenotypes. These data provide further evidence that, in IDDM, production and titre of major autoantibody specificities are associated with HLA class II alleles.
AB - Insulin, glutamate decarboxylase (GAD) and the protein tyrosine phosphatase-like molecule IA-2 are major targets of humoral autoimmunity in insulin-dependent diabetes mellitus (IDDM). These autoantibodies are heterogeneous with respect to age and patient human leukocyte antigen (HLA) phenotype. We have previously demonstrated that GAD and IA-2 antibodies potentially identify different subsets of IDDM patients. The aim of this study was to determine whether GAD and IA-2 autoantibodies were associated with different HLA DR phenotypes. We studied 160 patients with IDDM onset before age 16 years. At disease onset serum was tested for GAD and IA-2 antibodies by immunoprecipitation of in vitro-translated 35S-methionine labelled recombinant proteins. IA-2 antibodies were significantly associated with HLA DR4: 67 (86%) of 78 patients with HLA DR4 vs 31 (38%) of 82 non-DR4 patients had IA-2 antibodies (p(c) <0.0001) and IA-2 antibody levels were higher in patients with HLA DR4 (p(c) <0.0001). In contrast, GAD antibodies were more prevalent (p(c) <0.05) and antibody levels highest (p(c) <0.01) inpatients with HLA DR3 phenotypes. These data provide further evidence that, in IDDM, production and titre of major autoantibody specificities are associated with HLA class II alleles.
KW - Autoantibodies
KW - Glutamic acid decarboxylase
KW - HLA
KW - IA-2
KW - Insulin-dependent diabetes mellitus
UR - http://www.scopus.com/inward/record.url?scp=0029782272&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029782272&partnerID=8YFLogxK
M3 - Article
C2 - 8897011
AN - SCOPUS:0029782272
VL - 39
SP - 1223
EP - 1226
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 10
ER -