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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 human HLA-D histocompatibility region encodes class II antigens each of which consists of two polypeptide chains (alpha and beta) inserted in the plasma membrane. These molecules are implicated in the regulation of the immune response but several human diseases are also found to be associated with certain HLA-DR antigens. The occurrence of insulin-dependent (type I) diabetes (IDDM) is strongly associated with HLA-DR3 and/or 4 (ref. 5). The class II antigens, however, show a marked genetic polymorphism associated with the beta-chains which seem, from hybridization studies, to be encoded by several genes. We have therefore used the beta-chain cDNA probe, pDR-beta-1 (refs 8, 10) to test whether there are differences in hybridization pattern between DNA from healthy individuals and diabetic patients, after digestion with restriction endonucleases. Among the HLA-DR 4 and 3/4 individuals, the IDDM patients showed an increased frequency of a PstI 18 kilobase (kb) fragment. A BamHI 3.7 kb fragment, frequent among controls (30-40%), was rarely detected in the IDDM patients (0-2%). These differences may be related to susceptibility to develop the disease.
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PMID:HLA-D region beta-chain DNA endonuclease fragments differ between HLA-DR identical healthy and insulin-dependent diabetic individuals. 630 68

Seventeen newly diagnosed type 1 diabetics were studied longitudinally--at diagnosis, after 5 months and after 2 years, for antibodies against the following viruses: Coxsackie B3, B4 and B5, Echo 11, and Adeno 7a. The latter two were chosen because they had been isolated frequently in the area during the year the patients were diagnosed, whereas the Coxsackie viruses previously have been associated with the aetiology of type 1 diabetes. Coxsackie B4 antibody titres fell from the diagnosis and the 5 month study to the 2 year study (p less than 0.02), and, at this time, the average titre was also lower than in 37 healthy control individuals (p less than 0.05). Over the same period Coxsackie B3 antibody titres increased (p less than 0.05). Echo 11 antibody titres were higher in the patients at diagnosis (p less than 0.05), but, otherwise, no significant titre differences, compared with controls or titre changes, were found at any of the study times. Patients with lower suppressor cell activity at diagnosis displayed higher mean antibody titres regarding the five viruses together, than did patients with higher suppressor cell activity (p less than 0.05). No significant correlations were found between, on the one hand, the antibody titres and, on the other hand, C-peptide values, insulin dosage, degree of glycaemic control, or specific tissue type, HLA-B8 or HLA-DR3 and/or 4.
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PMID:A longitudinal study of virus antibodies in patients with newly diagnosed type 1 (insulin-dependent) diabetes mellitus. 632 89

Insulin dependent diabetes mellitus (IDDM) is closely associated with special MHC gene products. The class II gene products, HLA-DR3 and DR4, may be the primary susceptibility genes for IDDM. They mediate the pathogenetical immune mechanisms which, under the additional influence of special MHC-genes of class I and III, lead to diabetes. The extremely high frequency of HLA-DR3, DR4 heterozygotes among diabetic patients and the genetic heterogeneity in B8, DR3 positive patients on the one hand and B15, DR4 positive diabetics on the other with regard to various clinical, epidemiological and immunological parameters, point to the existence of at least two different diabetes susceptibility genes. They act synergistically when they occur together. Thus simple genetic models (autosomal dominant, autosomal recessive, gene dosage) do not appear to be relevant here. The increased diabetic risk for the identical siblings of DR3, DR4-positive patients offers a good opportunity of studying genetically influenced immune deviations in the prediabetic phase which result in the suppression and destruction of Beta cells and finally in the manifestation of diabetes.
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PMID:The HLA association of insulin-dependent (type I) diabetes mellitus. 633 38

In a prospective 21-year study, islet cell antibodies and beta cell function were serially assessed in 24 monozygotic twins initially discordant for type I diabetes mellitus. Eighteen of 21 twins typed had HLA-DR3 or HLA-DR4 antigens. During the follow-up, 4 twins developed type I diabetes mellitus, and in 3 of these 4 twins islet cell antibodies preceded the diagnosis of clinical diabetes mellitus by greater than 8, 5 and 7 years respectively. During the "prediabetic phase," the presence of islet cell antibodies was temporally associated with a progressive decline in first phase insulin response to intravenous glucose. Elevations in fasting blood glucose and abnormalities on oral glucose tolerance tests appeared only later during the course of the disease. Of the remaining 20 twins who continue to be discordant for type I diabetes mellitus, two have had islet cell antibodies for greater than 1.5 and 1 year respectively. One of these islet cell antibody-positive non-diabetic twins was restudied; despite a fasting blood glucose level of 64 mg/dL, she had a total absence of first phase insulin response to intravenous glucose. There was no evidence of transient islet cell antibody positivity in any of the twins studied. Type I diabetes mellitus in monozygotic twins has a prolonged prediabetic phase of progressive beta cell dysfunction with associated immunologic abnormalities.
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PMID:Type I diabetes mellitus in monozygotic twins: chronic progressive beta cell dysfunction. 635 87

In order to try to detect heterogeneity within insulin dependent diabetes mellitus (IDDM) and to distinguish a mode of inheritance of IDDM, population genetic analyses were performed using HLA allele frequencies. HLA-A and -B typing performed on 231 IDDM individuals and 268 controls from the southeastern U.S. showed significant increases with IDDM in A2, B8, B15 and B18, and significant decreases in Aw23, B7, B14 and B17. The combination of HLA-B8/B15 showed a greatly increased risk (RR = 25.5). Between the 120 IDDM individuals and 123 controls HLA-DR typed, HLA-DR3 and -DR4 were significantly increased among the IDDM group and DR2 and DR7 were decreased. The risk for DR3/4 was 29.2. It appeared that the B15 association was secondary to the DR4, but the B8/DR3 association showed no difference. Using the method of Curie-Cohen, no significant increases in risk were found for the B8/B15 or DR3/DR4 heterozygotes when compared to the respective homozygotes. Using the method of Thomson and Bodmer, the dominant mode of inheritance was excluded for DR4 only. There was a significant increase in B15 and DR4 in those with onset before age 20. No significant differences were found among the DR phenotypes with respect to season.
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PMID:Population genetic analyses of insulin dependent diabetes mellitus using HLA allele frequencies. 641 98

The typing of 22 HLA-A and B antigens in members of 13 families with one child having juvenile diabetes mellitus showed a statistically significant higher frequency of HLA-B8 antigen in sick children (51.54%) as well as high parental heredity rate of this antigen, as compared to 301 normal subjects and 51 normal children of families free from diabetes mellitus. The agreement of 85.71% in one or two haplotypes in diabetic and healthy siblings in 7 families involved antigens other than B8. The results of these family studies confirm the existing relationship between HLA-B8 and juvenile diabetes mellitus as demonstrated by repeated screenings of the patients populations. The relationship of HLA antigens to insulin-dependent juvenile diabetes mellitus has been studied by many authors. The issues of their studies on patient populations revealed HLA-DR3, Dw3, DR4, Dw4, B8, B18, B15, B40, Cw3 and secondarily A1 and A2 to occur with significantly higher frequency. On the other hand, antigens DR2, Dw2, B7 (secondarily A3 and A11) are statistically less frequent in this disease, and their presence therefore means a certain protection against the risk of diabetes (4, 6, 7, 11, 15, 21). Individual authors' family studies differ in conclusions as to the occurrence of some of the above HLA antigens, and the degree of HLA identity of two siblings, one with diabetes, the other one normal (6, 8, 12, 17). For this reason we decided to start investigations on the occurrence of HLA A and B antigens in family members with one child having juvenile diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:HLA and insulin-dependent juvenile diabetes mellitus. 641 92

We studied fifty patients with painless thyroiditis with transient thyrotoxicosis (PTTT) and a low radioiodine thyroidal uptake. In 25 PTTT occurred post-partum (P) and in the remainder was unrelated to pregnancy (U). Seventeen patients with classical subacute thyroiditis were studied for comparison. All patients were typed for HLA-A, B, C, DR antigens. Four of the P patients had recurrences with each pregnancy; two had one previous attack of U; three had a maternal history of Graves' disease; 76% of the P patients had small to moderate goitres and 76% antimicrosomal antibody titres at greater than 1:400. HLA-B35 was found in 24% of P patients compared to 17% of controls; 71% of patients with subacute thyroiditis were, by contrast, B35. Two of P were HLA-B8 positive (versus 25% of controls); 11 patients were HLA-DR3 positive and 15 (60%) HLA-DR5 positive compared to 23% and 27% of controls yielding a relative risk (RR) = 2.50 (P less than 0.05) and 3.83 (P less than 0.005), respectively. All four P patients with recurrences carried HLA-DR5. Thirteen of 25 patients in the U subgroup were HLA-DR3, yielding a RR = 3.38 (P less than 0.01); seven were HLA-DR5, with a non-significant RR = 1.12; four of U had first degree relatives with either autoimmune thyroid disorders or Type 1 diabetes mellitus. Thus, both P and U are associated with HLA-DR3, the P subgroup had in addition an increased frequency of DR5. The observed HLA associations for the PTTT syndromes favours an autoimmune rather than viral aetiology.
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PMID:Increased frequency of HLA-DR3 and 5 in the syndromes of painless thyroiditis with transient thyrotoxicosis: evidence for an autoimmune aetiology. 660 5

This report deals with the question of the susceptibility for IDD association with the recently described HLA-linked SB system. The SB system is located centromeric of HLA-DR between HLA-DR and GLO. At present five specificities of the SB system, which behave as alleles, can be recognized. A total of 40 IDD patients and 96 normal controls were characterized for HLA-A, -B, -C, -DR and SB antigens. Our results confirmed the strong positive association of IDD with HLA-DR3 and -DR4 and the negative association of IDD with HLA-DR2. The genetic analysis of the SB system and IDD, however, demonstrated no significant association between alleles of SB and susceptibility for IDD. The analysis of association between alleles of HLA-DR and SB revealed no significant linkage disequilibrium in IDD patients and a significant linkage disequilibrium between SB1 and HLA-DR3 in the controls. These results suggest that the genes associated with susceptibility for IDD are primarily coded for telomeric of SB and tightly linked with HLA-DR.
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PMID:Relation of insulin-dependent diabetes mellitus (IDD) and the HLA-linked SB system. 660 7

We have studied major histocompatibility complex markers in Caucasian patients with type I diabetes mellitus and their families. The frequencies of extended haplotypes that were composed of specific HLA-B, HLA-DR, BF, C2, C4A, and C4B allelic combinations, which occurred more commonly than expected, were compared on random diabetic and normal chromosomes in the study families. We demonstrated that all of the previously recognized increases in HLA-B8, B18, B15, DR3, and perhaps DR4 could be ascribed to the increase among diabetic haplotypes of a few extended haplotypes: [HLA B8, DR3, SC01, GLO2]; [HLA-B18, DR3, F1C30]; [HLA-B15, DR4, SC33]; and [HLA-BW38, DR4, SC21]. In fact, HLA-DR3 on nonextended haplotypes was "protective", with a relative risk considerably less than 1.0. There was a paucity or absence among diabetic patients of several extended haplotypes of normal chromosomes, notably [HLA-B7, DR2, SC31] and [HLA-BW44, DR4, SC30]. The extended haplotype [HLA-BW38, DR4, SC21] is found only in Ashkenazi Jewish patients, which suggests that extended haplotypes mark specific mutations that arise in defined ethnic groups. The data show that no known MHC allele, including HLA-DR3 and possibly HLA-DR4, is per se a marker for or itself a susceptibility gene for type I diabetes. Rather, extended haplotypes, with relatively fixed alleles, are either carriers or noncarriers of susceptibility genes for this disease. Thus, the increased frequency (association) or the decreased frequency (protection) of individual MHC alleles is largely explainable by these extended haplotypes.
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PMID:Extended major histocompatibility complex haplotypes in type I diabetes mellitus. 674 3

HLA studies have conclusively demonstrated that IDDM and non-IDDM are separate disease entities. A considerable part of the genetic susceptibility to IDDM is due to one or more HLA genes. The HLA-DR3 and -DR4 factors showing the strongest association with IDDM belong to the so-called DR antigens, which are believed to be the immune response determinants of man. A dominant model for the HLA-controlled susceptibility to IDDM has been ruled out and a recessive model seems unlikely. A gene-dose model intermediate between dominance and recessivity is still possible, but there is also some evidence against this model, because DR3/4 heterozygotes seem to have a considerably higher risk of developing IDDM than has DR3/3 and DR4/4 homozygotes. It has been suggested that DR3 (or a DR3-associated factor) and DR4 (or a DR4-associated factor) confer susceptibility to IDDM each by a separate mechanism, and more recently that DR3/4 heterozygotes may carry combinatorial antigens which could contribute to the susceptibility to IDDM. Studies of HLA-associated clinical heterogeneity within IDDM are indicated to gain further insight in the genetics of IDDM.
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PMID:HLA and diabetes. 676 95


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