UMLS:C0011854 - FACTA Search

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Query: UMLS:C0011854 (type 1 diabetes)
20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Basques were previously shown to present a high frequency of HLA-B18 and BfF1, which are known to be associated with insulin dependent diabetes mellitus (IDDM). During the VIII International Histocompatibility Workshop, we studied HLA-A, B, C, DR; Bf, C4 and GLO.I polymorphisms in 51 unrelated French Basque IDDM patients and in 50 controls. Haplotypes were established by family studies in all controls and some patients. Two haplotypes were frequently found in the controls: HLA-A1, Bw57, BfS, C4 F1S, DR7 and HLA-Aw30, Cw5, B18, Bf F1, C4Fs degree, DR3. The first one was not found in the patients. All the components of the second haplotype had increased frequencies possibly as a consequence of linkage disequilibrium with HLA-DR3: a highly significant association between IDDM and HLA-DR3 was observed (90.2% vs 24.0%, relative risk (RR) = 29.1, P less than 10(-11)). The HLA-DR4 frequency was slightly increased (37.3% vs 16.0%), and HLA-DR2 was not found. The silent allele C4s degree was particularly associated with early diagnosed IDDM (86.7% in patients with age at onset under 20 years vs 57.1% in other patients, P less than 0.02). The high relative risk for HLA-DR3/DR4 heterozygous vs that of individuals, possibly HLA-DR3 homozygous, supported the hypothesis that two HLA-DR linked genetic factors could be involved in the inheritance of IDDM susceptibility.
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PMID:HLA-A, B, C, DR antigens, Bf, C4 and glyoxalase I (GLO) polymorphisms in French Basques with insulin-dependent diabetes mellitus (IDDM). 695 94

Bacterial antigen fragments complexed with class II major histocompatibility molecules (HLA-D) on antigen presenting cells (APCs) stimulate CD4+ T lymphocyte proliferation, presumably to protect the host. This study examined these responses to antigens of two periodontal pathogens in four groups (n = 15) of age- (young adult) and sex-matched Caucasian subjects with or without type 1 diabetes and moderate to severe periodontitis: Group DP = diabetics with periodontitis; Group DnP = diabetics without periodontitis; Group nDP = nondiabetics with periodontitis; and Group nDnP = nondiabetics without periodontitis. HLA-D phenotypes for each subject were determined by lymphocytotoxicity assays. T lymphocytes purified from peripheral blood were stimulated in cell culture with APC pulsed with various concentrations of tetanus toxoid, Porphyromonas gingivalis, and Capnocytophaga sputigena antigens. T lymphocyte reactivity (3H thymidine incorporation) was numerically lower in cultures from diabetics stimulated with unpulsed APC (not significant), and antigen-pulsed cultures showed low proliferation and no significant differences among groups. Stimulation indices in cultures from diabetic patients stimulated with P. gingivalis or C. sputigena, however, were significantly elevated at all antigen concentrations compared to nondiabetic cultures. The occurrence of HLA-DR4 was moderately associated with diabetes (P < 0.05) and highly associated with periodontitis (P < 0.001, log-linear model for categorical variables); and HLA-DR53 and HLA-DQ3 were significantly associated with periodontitis (P < or = 0.02). HLA-DR was crucial to lymphocyte stimulation (anti-HLA-DR blocking experiments), but the low peripheral blood T cell reactivity to antigens of periodontal pathogens could not be linked with HLA-D type or periodontitis susceptibility.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HLA-D and T lymphocyte reactivity to specific periodontal pathogens in type 1 diabetic periodontitis. 827 7

Presence of autoimmune diseases and relationship of autoantibody expression with HLA association has been studied in 44 multicase rheumatoid arthritis (RA) families of Asian Indian origin. An increased prevalence of systemic lupus erythematosus (SLE) was observed in relatives (2.3%). Although HLA-DR4 segregated preferentially with seropositivity in general, no difference was observed among seropositive versus seronegative RA. On the other hand, no HLA association was observed with ANF positivity in these families. An increased frequency of DR7 in the ANF negative and RF negative group of RA patients compared to positive groups suggests that it may act as protective element for the development of autoantibodies in RA. An increased occurrence of DR4 in relatives affected with SLE was observed. While RA segregated mostly with HLA-DR4 in these families, autoimmune thyroid disease and insulin dependent diabetes mellitus (IDDM) segregated with HLA-DR3 suggesting the involvement of at least two sets of HLA-linked autoimmunity favouring susceptibility genes in the Indian population.
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PMID:Occurrence of autoimmune diseases and relationship of autoantibody expression with HLA phenotypes in multicase rheumatoid arthritis families. 835 6

In order to evaluate clinical presentation and to determinate classification criteria of type 1 diabetes in the elderly, we carried out a study in 258 diabetic patients more than 60 years old of which 100 used insulin by failure to oral hypoglycemic agents (OHA). The prevalence of ischemic cardiovascular disease was 36%, peripheral vascular disease 34% and stroke 30%. Non-proliferative retinopathy 47%, nephropathy 16% and peripheral neuropathy 37%. Cardiovascular risk factors as obesity (36%), hypertension (33%) and hypercholesterolemia (12%) were evaluated. The average duration of diabetes was 20 years. Post-glucagon C-Peptide, HLA-DR antigens and islet cell antibodies (ICA), were measured in 75 older diabetic patients on treatment of which 24 used insulin, 11 diet and 40 OHA. Older patients on treatment with insulin had longer duration of disease, less obesity, low level basal of C-Peptide and a low response to post glucagon C-Peptide (0.94 +/- 0.5 pmol/ml) compared with patients on diet (1.8 +/- 0.9 pmol/ml) and OHA (1.8 +/- 0.8 pmol/ml). Older diabetics on insulin therapy had a greater frequency of HLA-DR3 (42%) and HLA-DR4 (21%) than other older diabetics. The ICA was negative in most patients. This study shows the high prevalence of macrovascular and microvascular disease in elderly patients with diabetes mellitus and that the most reliable parameter in classifying type 1 (insulin-dependent) diabetes is the measurement of basal and post-glucagon C-Peptide. HLA-DR specific markers can be used with this parameter because their expression is partly shared. This approach appears useful in the older diabetic patients to help classify diabetes and its management.
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PMID:[Diabetes mellitus in the elderly: a study on its clinical presentation, C-peptide reserve, and immunogenetic markers of insulin dependence]. 848 59

The polymorphic variable number of tandem repeats in the 5' upstream region of the human insulin gene is a well-known non-human leukocyte antigen locus contributing to genetic susceptibility to IDDM. Controversy exists about the question as to whether INS susceptibility haplotypes are or are not preferentially inherited together with HLA-DR4 haplotypes. We investigated whether genetic interaction between INS and the HLA complex can be better defined using DQ genotypic and phenotypic markers in addition to DR serology. The 5' INS 1/1 genotype was positively associated with IDDM both in non-DR4 subjects (relative risk = 4.3; 95% confidence interval, 1.6-11.5) and DR4 subjects (relative risk = 4.2; 95% confidence interval, 1.9-9.0). Further subdivision of IDDM patients and matched control subjects according to HLA-DQA1 and HLA-DQB1 genotype or phenotype also failed to show any association between 5' INS and HLA class II genes in diabetic patients. The 5' INS and HLA class II polymorphisms therefore provide independent risk markers, which may both contribute to the genetic screening of a high-risk population among nondiabetic individuals.
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PMID:5' insulin gene polymorphism confers risk to IDDM independently of HLA class II susceptibility. 849 8

The polygenic susceptibility to type 1 diabetes is well established and recent studies have demonstrated linkage of a further locus on chromosome 2q to disease. We have studied a polymorphism of the interleukin-1 receptor type 1 gene (IL1R1) on chromosome 2q in type 1 diabetic and control subjects from Finland, the United Kingdom, South India: three populations in which the risk of disease varies from very high to very low. In the medium-risk U.K. population we find a very strong association of IL1R1 with type 1 diabetes (p = 0.0002) but we find no overall association in either the high-risk Finnish or low-risk South-Indian populations. However, we do find heterogeneity of risk at IL1R1 amongst Finnish diabetic subjects according to the possession of HLA-DR associated susceptibility (p = 0.0001); there is an association with IL1R1 in only those Finnish diabetic subjects who do not possess high-risk HLA-DR4 or DR3 haplotypes (p = 0.006), as recently demonstrated for the insulin gene region in this population. We find no such heterogeneity of risk in either the U.K. or South-Indian populations. This study further demonstrates the genetic heterogeneity of disease susceptibility between and within populations and also supports the hypothesis of an interaction of the IL1R1 locus with genes within the HLA and insulin gene regions in the susceptibility to type 1 diabetes.
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PMID:An association between type 1 diabetes and the interleukin-1 receptor type 1 gene. The DiMe Study Group. Childhood Diabetes in Finland. 891 96

Japanese IDDM patients have been demonstrated to have unique and different HLA associations from white patients. To elucidate the effect of HLA-associated genetic factors on the clinical heterogeneity of IDDM in Japanese people, HLA-DRB1, DQA1, and DQB1 genotypes in 88 childhood-onset Japanese IDDM patients were examined by polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) or sequence-specific primers (SSP). Of the 88 IDDM patients, 26 (29.5%) had DRB1*0405-DQA1*0302-DQB1*0401/X (DR4-DQ4/X), 38 (43.2%) had DRB1*0901-DQA1*0302-DQB1*0303/X (DR9-DQ9/X), and 9 (10.2%) were DR4/9-DQ4/9 heterozygous in the present study (X does not contain protective alleles). Clinical heterogeneity such as age distribution at onset, prevalence and serum level of anti-GAD antibodies (GADAb), and residual pancreatic beta-cell function after diagnosis were compared between patients with HLA-DR4-DQ4 and DR9-DQ9. The frequency of DR9-DQ9 genotype was significantly higher in the younger (0-10 years) than in the older (11-16 years) age-group of onset, but the frequency of DR4-DQ4 was higher in the older (11-16 years) age-group. Although no association of DR-DQ genotypes with the prevalence and serum level of GADAb was found among newly diagnosed patients, long-standing DR9-DQ9 patients had significantly higher levels of GADAb than those with DR4-DQ4. While no difference in time course of serum C-peptide (CPR) levels was detected between GADAb+ and GADAb- patients, a remarkable difference was demonstrated between DR9-DQ9 and DR4-DQ4 patients. The residual pancreatic beta-cell function was retained more in patients with DR4-DQ4 than in those with DR9-DQ9 at diagnosis through 12-18 months after diagnosis. These results suggest that the DR9-DQ9 genotype may induce stronger autoimmune destructive response (T-helper 1 function) against target beta-cells than the DR4-DQ4 genotype does. Our findings may warrant further studies on the association of diabetogenic autoimmune response with HLA class II molecules and contribute to a clarification of interracial differences in HLA-encoded susceptibility to IDDM.
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PMID:Association of HLA-DR, DQ genotype with different beta-cell functions at IDDM diagnosis in Japanese children. 935 42

Serum IgG responses to the cell envelope proteins (CEPs) from Capnocytophaga sputigena, Capnocytophaga ochracea, and Capnocytophaga gingivalis were examined in periodontally healthy and periodontitis subjects, both with and without type 1 diabetes (n = 60). Serum IgG responses to CEPs were determined by immunoblotting with biotin-goat anti-human IgG and an alkaline phosphatase-streptavidin system. Reactivity was analyzed by transmission densitometry, digitization, and computer manipulation. The patients with diabetes showed significantly (p < 0.01) fewer responses to 14 CEPs (from 81 to 10 kDa) from C. sputigena, 5 CEPs (from 90 to 17 kDa) from C. gingivalis, and the 27-kDa CEP from C. ochracea than in the non-diabetic group. The periodontitis patients showed significantly (p < 0.01) fewer responses to the 25- and 11-kDa CEPs from C. sputigena, the 125- and 17-kDa CEPs from C. gingivalis, and the 42-kDa CEP from C. ochracea than in the periodontally healthy group. HLA-DR4, HLA-DR53, and HLA-DQw3 were associated with periodontitis, while only HLA-DR4 was associated with diabetes (p < 0.02). Significant (p < 0.01) correlations were found between HLA-DR2 and IgG reactivity patterns associated with non-diabetics, and between HLA-DR4 and IgG reactivity patterns associated with diabetic and periodontitis subjects. These results indicate that both type 1 diabetics and periodontitis subjects have a depressed IgG antibody profile to Capnocytophaga, which may account for an increased susceptibility to periodontitis infection. Periodontitis in type 1 diabetes may be related more to the HLA-D type and altered immune function than to the diabetes itself.
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PMID:HLA-D types and serum IgG responses to Capnocytophaga in diabetes and periodontitis. 939 Apr 75

T cells recognize peptide epitopes bound to major histocompatibility complex molecules. Human T-cell epitopes have diagnostic and therapeutic applications in autoimmune diseases. However, their accurate definition within an autoantigen by T-cell bioassay, usually proliferation, involves many costly peptides and a large amount of blood. We have therefore developed a strategy to predict T-cell epitopes and applied it to tyrosine phosphatase IA-2, an autoantigen in IDDM, and HLA-DR4(*0401). First, the binding of synthetic overlapping peptides encompassing IA-2 was measured directly to purified DR4. Secondly, a large amount of HLA-DR4 binding data were analysed by alignment using a genetic algorithm and were used to train an artificial neural network to predict the affinity of binding. This bioinformatic prediction method was then validated experimentally and used to predict DR4 binding peptides in IA-2. The binding set encompassed 85% of experimentally determined T-cell epitopes. Both the experimental and bioinformatic methods had high negative predictive values, 92% and 95%, indicating that this strategy of combining experimental results with computer modelling should lead to a significant reduction in the amount of blood and the number of peptides required to define T-cell epitopes in humans.
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PMID:Strategies for identifying and predicting islet autoantigen T-cell epitopes in insulin-dependent diabetes mellitus. 945 87

Approximately one-half of Caucasians with newly diagnosed insulin-dependent diabetes mellitus (IDDM) have autoantibodies to insulin, and the majority of those express the HLA-DR4 genotype [Ziegler, R., Alper, C. A., Awdeh, Z. L., Castano, L., Brink, S. J., Soeldner, J. S., Jackson, R. A. & Eisenbarth, G. S. (1991) Diabetes 40, 709-714]. However, it has been difficult to demonstrate T cell proliferative responses to human insulin in IDDM patients [Durinovic-Bello, I., Hummel, M. & Ziegler, A. G. (1996) Diabetes 45, 795-800]. We have immunized transgenic mice expressing the susceptible HLA-DR (alpha1*0101,beta1*0401) (hereafter called DRB1*0401) and human CD4 molecules on a murine major histocompatibility complex class II null background, with human preproinsulin (PPI), proinsulin (PI), and insulin and derived large panels of T cell hybridomas to determine the immunogenic epitopes of these proteins. These results show that the prohormones PI or PPI carry the major immunogenic T cell epitope in the DRB1*0401 transgenic mice. The PPI/PI immunodominant epitope LALEGSLQK was localized at the C-peptide/A-chain junction. This T cell epitope PPI/PI LALEGSLQK is unusual because, normally, it is proteolytically destroyed during the maturation of the insulin molecule. Additionally, this T cell epitope is both processed and presented by human DRB1*0401-positive Epstein-Barr virus transformed B cells, and it can also stimulate T cells from the peripheral blood of HLA-DR4-positive patients with type 1 diabetes. These findings may partly explain why susceptibility to type 1 diabetes is associated with HLA-DR4-positive individuals and why T cell responses to the mature insulin protein are rarely detected in IDDM patients.
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PMID:T cell epitopes of insulin defined in HLA-DR4 transgenic mice are derived from preproinsulin and proinsulin. 952 Apr 53

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