HLA-DR, DQ and anti-GAD antibodies in first degree relatives of type I diabetes mellitus

Serrano-Rı́os, Manuel; Pérez-Bravo, F; Martínez, Miguel S. Vallés; Antona, Jlenia; Rowley, Merrill J.; Mackay, Ian R.; Zimmet, Paul

doi:10.1016/s0168-8227(96)90020-0

Cited by 13 publications

(7 citation statements)

References 22 publications

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“…The frequency of high-risk alleles DQB1*02, DQB1*0302 and DQA1*0301 increased in type 1 diabetic patients. We also confirmed the high frequency of HLA-DQ risk alleles in firstdegree relatives [20,21,22].…”

Section: Discussionsupporting

confidence: 81%

Markers for Risk of Type 1 Diabetes in Relatives of Alsacian Patients With Type 1 Diabetes

Ongagna

Sapin

Pinget

et al. 2000

Journal of Diabetes Research

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Background: The cytotoxic T lymphocyteassociated antigen 4 gene (CTLA-4) encode the T cell receptor involved in the control of T cell proliferation and mediates T cell apoptosis. The receptor protein is a specific T lymphocyte surface antigen that is detected on cells only after antigen presentation. Thus, CTLA-4 is directly involved in both immune and autoimmune responses and may be involved in the pathogenesis of multiple T cell-mediated autoimmune disorders. There is polymorphism at position 49 in exon 1 of the CTLA-4 gene, providing an A-G exchange. Moreover, we assessed the CTLA-4 49 (Thr/Ala) polymorphism in diabetic patients and first-degree relatives as compared to control subjects. Research design and methods: Three loci (HLA-DQB1, DQA1 and CTLA-4) were analysed in 62 type 1 diabetic patients, 72 firstdegree relatives and 84 nondiabetic control subjects by means of PCR-RFLP. Results: A significant enrichment in DQB1 alleles encoding for an amino acid different from Asp in position 57 (NA) and DQA1 alleles encoding for Arg in position 52 was observed in diabetic subjects and first-degree relatives as compared to controls. The genotype and allele frequencies of these polymorphisms in type 1 diabetic patients and firstdegree relatives differed significantly from those of controls (p< 0.001 and 0.05 respectively). CTLA-49 Ala alleles frequencies were 75.8% in type 1 diabetic patients and 68.1% in first-degree relatives in comparison to 35.7% in control subjects. The Ala/Ala genotype conferred a relative risk of 18.8 (p < 0.001). Conclusion: The CTLA-4 49 Ala allele confers an increased risk of type 1 diabetes, independent of age and HLA-DQ genetic markers.

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Section: Discussionsupporting

confidence: 81%

Markers for Risk of Type 1 Diabetes in Relatives of Alsacian Patients With Type 1 Diabetes

Ongagna

Sapin

Pinget

et al. 2000

Journal of Diabetes Research

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“…All these findings suggest that anti-GAD can be a potentially useful predictive marker for type 1 diabetes. [16][17][18][19] To the best of our knowledge, this is the first study to determine the prevalence of anti-GAD not only in Syrian and Jordanian populations but in the rest of the Arab World and the Near East as well. Anti-GAD prevalence rates were significantly higher in Syrian and Jordanian type 1 diabetes patients and siblings than in their corresponding control groups (P<0.001, P <0.0001, P=0.002, respectively).…”

Section: Discussionmentioning

confidence: 97%

“…15,16 In addition, we found no correlation between sex and the positivity of anti-GAD, a finding also reported in several other studies. 17 Two reports found a female preponderance of anti-GAD, the first a report from Australia (75% females vs 63% males, P=0.03) 18 and the second from Sweden (79% females vs 63% males, P<0.001.) The highest frequency of anti-GAD in type 1 diabetes patents was in the age group 13 to 16 years, while in the IDDM siblings it was highest in the two age groups 5 to 8 and 13 to 16 years ( Figure 1).…”

Section: Discussionmentioning

confidence: 97%

“…More recent studies have shown that there is a positive association between anti-GAD and DQ alleles. [14][15][16][17][18][19][20][21][22][23][24][25][26]27 Thus it would be important to determine the susceptible alleles that correlate highly with the positivity of anti-GAD among Syrian and Jordanian populations. This issue is currently being investigated.…”

Section: -22mentioning

confidence: 99%

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Antibodies to Glutamic Acid Decarboxylase in Syrian and Jordanian Type 1 Diabetes Patients and their Siblings

et al. 2003

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Background: Attempts to identify the earliest events in the autoimmune process in type 1 diabetes mellitus suggest that glutamic acid decarboxylase (GAD) is one of the first and most important autoantigens. We conducted this study to determine the prevalence of antibodies to glutamic acid decarboxylase (anti-GAD) in both Syrian and Jordanian children with Type 1 diabetes and their siblings. Patients and Methods: Sera were obtained from 85 Syrian patients with type 1 diabetes (mean age, 13.6±5.9 years), from 45 of their siblings (mean age, 11.3±6.1 years), from 78 randomly selected Syrian control subjects (mean age, 9.9±43 years), and from 95 Jordanian patients with type 1 diabetes (mean age 13.9±65 years), from 78 of their siblings (mean age 12.3±7.1 years), and from 100 randomly selected Jordanian control subjects (mean age, 7.8±4.5 years). Sera were analyzed for anti-GAD using the enzyme linked immunosorbent assay (ELISA) technique. Results: Prevalence of anti-GAD was 34.1% (29/85) in Syrian type 1 diabetes patients, 20% (9/45) in their siblings, 1.3% (1/78) in Syrian control subjects, 49.5% (47/95) in Jordanian type 1 diabetes patients, 23% (18/78) in their siblings, and 2% (2/100) in Jordanian control subjects. Differences between the Syrian and Jordanian type 1 diabetes groups and their siblings and controls were statistically significant. In patients with less than two years of diabetes duration, the frequency was 88.8% (16/18) for both groups. There was no correlation between sex and anti-GAD levels in either Syrian and Jordanian type 1 diabetes patients and their siblings. The positivity of anti-GAD tended to be more frequent at the age range of 5 to 8 years in siblings. Anti-GAD titers >90 ng/mL were found in 58.8% of type 1 diabetes patients and in 38% of siblings who were anti-GAD positive. Conclusion: Syria and Jordan have prevalence rates of anti-GAD among type 1 diabetes patients and their siblings that are among the highest reported in the world. Therefore, anti-GAD may be valuable as an early predictive marker for Type 1 diabetes. Ann Saudi Med 23 (6): 376-380

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“…The presence of two or more of the autoantibodies is associated with a high risk of developing diabetes, whereas a single islet cell-related autoantibody usually has a low predictive value [6,14,21]. Furthermore, an association between autoantibodies and HLA class II alleles has been shown to significantly impact the risk of T1DM, although considerable variations exist among the type of autoantibodies and HLA-DR and -DQ genotypes [22][23][24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

Autoantibodies and High-Risk HLA Susceptibility Markers in First-Degree Relatives of Brazilian Patients with Type 1 Diabetes Mellitus: A Progression to Disease Based Study

et al. 2012

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HLA-DR, DQ and anti-GAD antibodies in first degree relatives of type I diabetes mellitus

Cited by 13 publications

References 22 publications

Markers for Risk of Type 1 Diabetes in Relatives of Alsacian Patients With Type 1 Diabetes

Markers for Risk of Type 1 Diabetes in Relatives of Alsacian Patients With Type 1 Diabetes

Antibodies to Glutamic Acid Decarboxylase in Syrian and Jordanian Type 1 Diabetes Patients and their Siblings

Autoantibodies and High-Risk HLA Susceptibility Markers in First-Degree Relatives of Brazilian Patients with Type 1 Diabetes Mellitus: A Progression to Disease Based Study

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