Autoimmunity to CD38 and GAD in Type I and Type II diabetes: CD38 and HLA genotypes and clinical phenotypes
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/325737
- author
- Antonelli, A ; Tuomi, Tiinamaija LU ; Nannipieri, M ; Fallahi, P ; Nesti, C ; Okamoto, H ; Groop, Leif LU and Ferrannini, E
- organization
- publishing date
- 2002
- 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
- external identifiers
-
- wos:000178526300012
- pmid:12242463
- scopus:0036383410
- pmid:12242463
- 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
- 2016-04-01 12:04:48
- date last changed
- 2024-01-08 07:36:11
@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<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}}, keywords = {{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}}, 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}}, doi = {{10.1007/s00125-002-0886-6}}, volume = {{45}}, year = {{2002}}, }