13 research outputs found
Studies on autoimmune diabetes in Latvians and other populations
IDDM is an autoimmune disease, characterized by autoimmune mediated loss
of insulin secreting B- cells. GAD65 and IA-2 are major B-cell specific
autoantibodies and are not found in healthy population. IDDM is
associated with certain HLA class II alleles. IDDM is positively
associated with HLA DR3 and DR4 in Caucasians. From HLA-DQ molecules, DQ8
(DQA1*0301- DQB1*0302) is the most prevalent IDDM haplotype in
Caucasians, followed by DQ2 (DQA1*0201-DQB1*0501). Taken together, DQ8,
DQ2 or both account for as many as 89% of Caucasian IDDM patients. DQ6
(DQA1*0102 DQB1*0602) is associated with the protection against IDDM in
most populations.
A certain group of NIDDM patients doesn't respond to oral hypoglycemic
treatment and insulin therapy is required. Majority becomes insulin -
deficient because of autoimmune B- cell destruction. It is described as
latent autoimmune diabetes in adults (LADA) or slow - onset Type 1
(autoimmune) diabetes.
MRDM as a separate form if diabetes mellitus, described in tropical
regions and associated with undenutrition. The question remains if
autoimmunity and genetic markers are associated with the development of
MRDM.
The aim of this thesis was to investigate prevalence of different HLA
class 11 molecules in different types of diabetes and different
populations to answer the question if autoimmune diabetes is similar in
most populations and if different genetic background in general
population is responsible for different incidence of IDDM.
Another question was if GAD65 and IA-2 are main autoantigens in IDDM and
autoantibodies against them are associated with IDDM, irrespective of
ethnic background. And final question was if slow-onset autoimmunity is
present among patients diagnosed as NIDDM in different populations.
The study on HLA markers showed that DR3-DQ2 and DR4-DQ8 were positively
associated with the disease in Latvian diabetics. The negatively
associated DQ taken together were present in more than 75% of healthy
controls. The excess frequency of the negative associated DQ molecules in
the general population could explain the lower incidence of IDDM in
Latvia.
Indian diabetics showed positive association of IDDM with DR3 and DQ2 but
not DR4 and DQ8. DQ6 (A*0102-B*0601) showed to be negatively associated
with IDDM in South Indians. In the MRDM group - PDDM patients showed
positive association with DR3 and DQ2, while FCPD patients had
association with DR7 and DQ9.
GAD65ab were present in 57% of South Indian IDDM patients while 97% of
Latvian IDDM patients carried either GAD65 or IA-2 autoantibodies. 55% of
NIDDM patients carried one of the autoantibodies suggesting high
prevalence of slow onset autoimmunity. Antibodies against minor
autoantigens (TTG and 21-OH) add 1% of positivity in IDDM group. Still
10% of IDDM patients are negative for any of analyzed autoantibodies,
suggesting involvement of other possible autoantigens. Antibodies against
new beta cell antigen ICA12 (SOX13) alone, are present in only 3% of IDDM
patients and 1% of NIDDM patients and adding ICA12ab to GAD65 and IA-2ab,
gives only 1% increase in antibody positivity in both IDDM and NIDDM
groups both in Latvian and Swedish diabetics
ICA12 Autoantibodies Are Associated with Non-DR3/Non-DR4 in Patients with Latent Autoimmune Diabetes in Adults from Northern India
MHC Class I Chain-Related Gene A Alleles Distinguish Malnutrition-Modulated Diabetes, Insulin-Dependent Diabetes, and Non-Insulin- Dependent Diabetes Mellitus Patients from Eastern India
Prevalence of ICA-12 and other autoantibodies in north Indian patients with early-onset diabetes
This study attempts to assess the prevalence of various autoantibodies in early-onset diabetics in northern India, with emphasis on antibodies against glutamic acid decarboxylase (GAD65), IA-2, ICA-12, 21-hydroxylase (21-OH) and Tissue Transglutaminase (TTG). GAD65 and IA-2 antibodies were found to be present in approximately 26% of cases of type 1 diabetes. A subset of patients clinically diagnosed to have MMDM appears to have an autoimmune etiology, with more than 20% showing serpositivity for IA-2 antibodies. Antibodies against ICA-12 were prevalent in both type 1 diabetes and MMDM. Approximately one of seven patients with type 1 diabetes showed erological evidence of celiac disease
ICA12 autoantibodies are associated with non-DR3/non-DR4 in patients with latent autoimmune diabetes in adults from northern India
Associations of HLA-DR3/DQ2 with GAD65 and DR4 with IA-2 antibodies in Insulin-dependent Diabetes Mellitus (IDDM) and DR3/DQ2 with GAD65 antibodies in Latent Autoimmune Diabetes in Adult (LADA) patients are known. The aim of the present study was to look for association of HLA DR and DQ with GAD65, IA2 and ICA12 antibodies in IDDM (n = 97), LADA (n = 32) and Malnutrition-modulated Diabetes Mellitus (MMDM) (n = 22) patients from northern India. HLA genotyping was done by the PCR-SSO method. Antibodies to GAD65, IA-2 and ICA-12 were assayed by radioimmunoassay using <sup>35</sup>S-labeled recombinant human GAD65, IA2 and ICA12 using the in vitro transcription-translation method. We found DR3 (29% vs. 11%) and DQ2 (36% vs. 14%) were increased in GAD65 antibody-positive compared to GAD65 antibody-negative IDDM patients (P > 0.05). ICA 12 antibodies were increased in either DR3 or DR4 (84% vs. 69%) positives compared to non-DR3/DR4 IDDM patients (P > 0.05). However in LADA patients, ICA12 was increased in non-DR3/DR4 patients compared to DR3- or DR4-positive patients (P < 0.05). In conclusion, in LADA patients, ICA 12 is associated with non-DR3/DR4 patients. No association between HLA and autoantibodies was seen in MMDM patients