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Autoimmunity to CD38 and GAD in Type I and Type II diabetes: CD38 and HLA genotypes and clinical phenotypes

Antonelli, A; Tuomi, Tiinamaija LU ; Nannipieri, M; Fallahi, P; Nesti, C; Okamoto, H; Groop, Leif LU and Ferrannini, E (2002) In Diabetologia 45(9). p.1298-1306
Abstract
Aims/hypothesis. Autoantibodies against CD38 have been found in some patients with Type II (non-insulin-dependent) diabetes mellitus and have been shown to stimulate insulin secretion by cultured human islets. We tested whether this new form of autoimmunity, (i) overlaps with anti-GAD autoimmunity, (ii) identifies an insulin-deficient phenotype, (iii) is under the influence of genetic factors. Methods. We screened 496 adults by immuno-blot analysis in the Botnia Study (298 with Type II and 98 with Type I (insulin-dependent) diabetes mellitus, 100 non-diabetic control subjects). Results. CD38-autoantibodies were found in 8.4% of Type II diabetic patients (p<0.003 vs 0% of control subjects), particularly in anti-GAD positive (14% vs 6% of... (More)
Aims/hypothesis. Autoantibodies against CD38 have been found in some patients with Type II (non-insulin-dependent) diabetes mellitus and have been shown to stimulate insulin secretion by cultured human islets. We tested whether this new form of autoimmunity, (i) overlaps with anti-GAD autoimmunity, (ii) identifies an insulin-deficient phenotype, (iii) is under the influence of genetic factors. Methods. We screened 496 adults by immuno-blot analysis in the Botnia Study (298 with Type II and 98 with Type I (insulin-dependent) diabetes mellitus, 100 non-diabetic control subjects). Results. CD38-autoantibodies were found in 8.4% of Type II diabetic patients (p<0.003 vs 0% of control subjects), particularly in anti-GAD positive (14% vs 6% of anti-GAD negative, p=0.0004). CD38ab were also found in 4% of Type I diabetic patients; in the whole study group, 59% of anti-CD38 positive had DQB1 *02 compared with 38% of anti-CD38 negative (p=0.04). On the OGTT, beta-cell function (as the ratio of insulin-to-glucose areas) was impaired (p=0.02) only in association with anti-GAD positivity (3.2 +/- 3.1 U/mol, mean +/- SD) but not in anti-CD38 positive patients (5.6 +/- 2.9) as compared with patients free of autoimmunity (4.5 +/- 4.6, p=NS). In 44 Type II diabetic patients (22 negative and 22 positive for anti-CD38), no mutations were detected in any of the 8 exons, 5' end of intron 1 or the 5' and 3' untranslated regions of the CD38 gene. The previously described missense mutation (Arg140Trp) in exon 3 was not found in this cohort. There was no association between the PvUII polymorphism and clinical phenotype. Conclusion. Anti-CD38 autoimmunity identifies a clinical phenotype similar to non-autoimmune Type II diabetes, with relative preserved beta-cell function and weak genetic influence. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
insulin secretion, CD38 polymorphisms, missense mutation, Type I diabetes mellitus, Type II diabetes mellitus, GAD antibodies, CD38 antibodies, CD38 gene, LADA, HLA
in
Diabetologia
volume
45
issue
9
pages
1298 - 1306
publisher
Springer Verlag
external identifiers
  • wos:000178526300012
  • pmid:12242463
  • scopus:0036383410
ISSN
1432-0428
DOI
10.1007/s00125-002-0886-6
language
English
LU publication?
yes
id
788c7282-9318-4012-bfb9-5b59c75454de (old id 325737)
date added to LUP
2007-08-02 11:40:34
date last changed
2017-08-13 03:37:45
@article{788c7282-9318-4012-bfb9-5b59c75454de,
  abstract     = {Aims/hypothesis. Autoantibodies against CD38 have been found in some patients with Type II (non-insulin-dependent) diabetes mellitus and have been shown to stimulate insulin secretion by cultured human islets. We tested whether this new form of autoimmunity, (i) overlaps with anti-GAD autoimmunity, (ii) identifies an insulin-deficient phenotype, (iii) is under the influence of genetic factors. Methods. We screened 496 adults by immuno-blot analysis in the Botnia Study (298 with Type II and 98 with Type I (insulin-dependent) diabetes mellitus, 100 non-diabetic control subjects). Results. CD38-autoantibodies were found in 8.4% of Type II diabetic patients (p&lt;0.003 vs 0% of control subjects), particularly in anti-GAD positive (14% vs 6% of anti-GAD negative, p=0.0004). CD38ab were also found in 4% of Type I diabetic patients; in the whole study group, 59% of anti-CD38 positive had DQB1 *02 compared with 38% of anti-CD38 negative (p=0.04). On the OGTT, beta-cell function (as the ratio of insulin-to-glucose areas) was impaired (p=0.02) only in association with anti-GAD positivity (3.2 +/- 3.1 U/mol, mean +/- SD) but not in anti-CD38 positive patients (5.6 +/- 2.9) as compared with patients free of autoimmunity (4.5 +/- 4.6, p=NS). In 44 Type II diabetic patients (22 negative and 22 positive for anti-CD38), no mutations were detected in any of the 8 exons, 5' end of intron 1 or the 5' and 3' untranslated regions of the CD38 gene. The previously described missense mutation (Arg140Trp) in exon 3 was not found in this cohort. There was no association between the PvUII polymorphism and clinical phenotype. Conclusion. Anti-CD38 autoimmunity identifies a clinical phenotype similar to non-autoimmune Type II diabetes, with relative preserved beta-cell function and weak genetic influence.},
  author       = {Antonelli, A and Tuomi, Tiinamaija and Nannipieri, M and Fallahi, P and Nesti, C and Okamoto, H and Groop, Leif and Ferrannini, E},
  issn         = {1432-0428},
  keyword      = {insulin secretion,CD38 polymorphisms,missense mutation,Type I diabetes mellitus,Type II diabetes mellitus,GAD antibodies,CD38 antibodies,CD38 gene,LADA,HLA},
  language     = {eng},
  number       = {9},
  pages        = {1298--1306},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Autoimmunity to CD38 and GAD in Type I and Type II diabetes: CD38 and HLA genotypes and clinical phenotypes},
  url          = {http://dx.doi.org/10.1007/s00125-002-0886-6},
  volume       = {45},
  year         = {2002},
}