scholarly journals Critical Amino Acid Variants in HLA-DRB1 and -DQB1 Allotypes in the Development of Classical Type 1 Diabetes and Latent Autoimmune Diabetes in Adults in the Japanese Population

2021 ◽  
Vol 43 (1) ◽  
pp. 107-115
Author(s):  
Masahito Katahira ◽  
Taku Tsunekawa ◽  
Akira Mizoguchi ◽  
Mariko Yamaguchi ◽  
Kahori Tsuru ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Amino Acid ◽  
Japanese Population ◽  
Autoimmune Diabetes ◽  
Human Leukocyte ◽  
Classical Type ◽  
Critical Amino Acid ◽  
Latent Autoimmune Diabetes ◽  
Amino Acid Variants

The effects of amino acid variants encoded by the human leukocyte antigen (HLA) class II on the development of classical type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA) have not been fully elucidated. We retrospectively investigated the HLA-DRB1 and -DQB1 genes of 72 patients with classical T1D and 102 patients with LADA in the Japanese population and compared the frequencies of HLA-DRB1 and -DQB1 alleles between these patients and the Japanese populations previously reported by another institution. We also performed a blind association analysis with all amino acid positions in classical T1D and LADA, and compared the associations of HLA-DRB1 and -DQB1 amino acid positions in classical T1D and LADA. The frequency of DRß-Phe-13 was significantly higher and those of DRß-Arg-13 and DQß-Gly-70 were significantly lower in patients with classical T1D and LADA than in controls. The frequencies of DRß-His-13 and DQß-Glu-70 were significantly higher in classical T1D patients than in controls. The frequency of DRß-Ser-13 was significantly lower and that of DQß-Arg-70 was significantly higher in LADA patients than in controls. HLA-DRß1 position 13 and HLA-DQß1 position 70 could be critical amino acid positions in the development of classical T1D and LADA.

scholarly journals Latent Autoimmune Diabetes in Adults Differs Genetically From Classical Type 1 Diabetes Diagnosed After the Age of 35 Years

Diabetes Care ◽  
2010 ◽  
Vol 33 (9) ◽  
pp. 2062-2064 ◽  
Author(s):  
M. K. Andersen ◽  
V. Lundgren ◽  
J. A. Turunen ◽  
C. Forsblom ◽  
B. Isomaa ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Autoimmune Diabetes ◽  
Classical Type ◽  
Latent Autoimmune Diabetes

scholarly journals HLA Genetic Discrepancy Between Latent Autoimmune Diabetes in Adults and Type 1 Diabetes: LADA China Study No. 6

2016 ◽  
Vol 101 (4) ◽  
pp. 1693-1700 ◽  
Author(s):  
Shuoming Luo ◽  
Jian Lin ◽  
Zhiguo Xie ◽  
Yufei Xiang ◽  
Peilin Zheng ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
High Risk ◽  
Aspartic Acid ◽  
Odds Ratio ◽  
Autoimmune Diabetes ◽  
Human Leukocyte ◽  
Data Set ◽  
Latent Autoimmune Diabetes ◽  
In Cis

Abstract Context: The discrepancies in terms of human leukocyte antigen (HLA)-DRB1-DQA1-DQB1 conferred risks between latent autoimmune diabetes in adults (LADA) and type 1 diabetes (T1D) patients remained almost completely unknown. The goal of the current study is to determine and compare HLA-conferred risks between LADA and T1D. Design: A case-control study was conducted in a representative Chinese data set containing 520 T1D patients, 562 LADA patients, and 1065 controls. The frequencies and odds ratios for HLA susceptible haplotypes and genotypes and for arginine at residue 52 in the DQ-α chain or aspartic acid at residue 57 in the DQ-β chain were analyzed. Results: DRB1*0405-DQA1*03-DQB1*0401 and DRB1*0901-DQA1*03-DQB1*0303 are the major LADA susceptible haplotypes, which also confer comparable risks for T1D (odds ratio 2.02 vs 2.20 and 1.61 vs 2.30, respectively). The strongly associated T1D haplotype DRB1*0301-DQA1*05-DQB1*0201 is also associated with LADA but confers only half of the T1D risk (odds ratio 2.65 vs 4.84). Interestingly, the most susceptible T1D haplotypes, DRB1*0901-DQA1*05-DQB1*0201, DRB1*0301-DQA1*03-DQB1*0201, and DRB1*0301-DQA1*03-DQB1*0303, are not associated with LADA. Genotypes for DR3/DR3, DR3/DR9, and DR9/DR9 are highly associated with T1D susceptibility, whereas only DR9/DR9 confers risk for LADA. DR3/DR3 is the high-risk genotype in Chinese T1D patients, which manifests similar risk as the DR3/DR4 genotype in Caucasians but with a lower frequency. DR9/DR9 is the high risk LADA genotype in Chinese. Alleles with DQ-α arginine at residue 52-positive, DQ-β aspartic acid at residue 57-negative, and their combination formed in cis or trans confer susceptibility to T1D but not to LADA. Conclusion: Our results suggest that LADA risk conferred by HLA-DRB1-DQA1-DQB1 loci in Chinese differs significantly from that of T1D risk. This information would be useful for classifying Asian LADA patients, which should provides novel insight into the understanding of its pathoetiology as well.

Type 1 Diabetes-related Autoantibodies in Different Forms of Diabetes

2019 ◽  
Vol 15 (3) ◽  
pp. 199-204 ◽  
Author(s):  
Elin Pettersen Sørgjerd
Keyword(s):  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Autoimmune Diabetes ◽  
Acid Decarboxylase ◽  
Adult Onset ◽  
Latent Autoimmune Diabetes ◽  
Childhood Type 1 Diabetes ◽  
Childhood Type

Autoantibodies against Glutamic Acid Decarboxylase (GADA), insulinoma antigen-2 (IA- 2A), insulin (IAA) and the most recently Zinc Transporter 8 (ZnT8A) are one of the most reliable biomarkers for autoimmune diabetes in both children and adults. They are today the only biomarkers that can distinguish Latent Autoimmune Diabetes in Adults (LADA) from phenotypically type 2 diabetes. As the frequency of autoantibodies at diagnosis in childhood type 1 diabetes depends on age, GADA is by far the most common in adult onset autoimmune diabetes, especially LADA. Being multiple autoantibody positive have also shown to be more common in childhood diabetes compared to adult onset diabetes, and multiple autoantibody positivity have a high predictive value of childhood type 1 diabetes. Autoantibodies have shown inconsistent results to predict diabetes in adults. Levels of autoantibodies are reported to cause heterogeneity in LADA. Reports indicate that individuals with high levels of autoantibodies have a more type 1 diabetes like phenotype and individuals with low levels of autoantibody positivity have a more type 2 diabetes like phenotype. It is also well known that autoantibody levels can fluctuate and transient autoantibody positivity in adult onset autoimmune diabetes have been reported to affect the phenotype.

A form of Autoimmune Diabetes in Adults Named LADA – An Update on Essential Features and Controversies

2019 ◽  
Vol 15 (3) ◽  
pp. 172-173 ◽  
Author(s):  
Valdemar Grill ◽  
Bjørn O. Åsvold
Keyword(s):  
Genetic Background ◽  
Clinical Utility ◽  
Autoimmune Diabetes ◽  
Classical Type ◽  
Phenotypic Characteristics ◽  
Latent Autoimmune Diabetes ◽  
The Impact

Latent Autoimmune Diabetes in the Adult, LADA has been investigated less than “classical” type 1 and type 2 diabetes and the criteria for and the relevance of a LADA diagnosis has been challenged. Despite the absence of a genetic background that is exclusive to LADA, this form of diabetes displays phenotypic characteristics that distinguish it from other forms of diabetes. LADA is heterogeneous in terms of the impact of autoimmunity and lifestyle factors, something that poses problems as to therapy and follow-up perhaps particularly in those with marginal positivity. Yet, there appears to be clear clinical utility in classifying individuals as LADA.

scholarly journals ELISA based on peptide antigens reproducing cross-reactive viral epitopes to detect antibodies in Latent Autoimmune Diabetes in Adults vs. Type 1 Diabetes

MethodsX ◽  
2021 ◽  
pp. 101452
Author(s):  
Feliciana Real-Fernández ◽  
Alessandra Gallo ◽  
Francesca Nuti ◽  
Lorenzo Altamore ◽  
Gloria Giovanna Del Vescovo ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Autoimmune Diabetes ◽  
Peptide Antigens ◽  
Latent Autoimmune Diabetes
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