Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin dependent diabetes mellitus (IDDM) is known to associate with various antigens and alleles of the HLA-system: DR3, DR4, and DQ-determinants. However penetration of the HLA-genes, predisposing to disease, is low, suggesting a possible role of additional genes outside the HLA-system in IDDM development. Among such genes there can be a group of heavy chain Ig genes (the Gm-system). The frequency of antigens of the Gm-system C1m(1) and C1m(2) and antigens of loci A, B, C and DR of the HLA-system was investigated in 92 Russians divided into 3 groups: 1 - IDDM patients from nuclear families (n = 35); 2 - their relatives of the 1st degree of kinship (n = 34); 3 - a random sampling (n = 23). The results obtained by A. A. Lopatenok and O. S. Budyakov (1973) were used as control data. No significant difference (p greater than 0.05) was found while comparing the frequency of Gm-phenotypes in IDDM patients from nuclear families with DR 4/X and in IDDM patients from nuclear families with another DR-phenotype, nor any significant difference was noted while comparing the frequency of Gm-phenotypes in IDDM patients from nuclear families and in patients from a random sampling with the HLA-phenotype DR 4/X. Thus the relationship of the Gm-system with IDDM through interrelationship with the HLA-DR-genes was undetectable. A conclusion was made that factors of the Gm-system played no significant role in predisposition to IDDM and could not be used as its genetic markers.
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PMID:[Probability of an association between HLA- and DR-antigens in nuclear families of patients with insulin-dependent diabetes mellitus]. 151 80

A significant increase in the prevalence of selective IgA deficiency has been observed in patients with autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis. Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease and susceptibility to both IDDM and IgA deficiency is associated with HLA DQB1 alleles encoding non-Asp amino acids at position 57. In order to assess whether the prevalence of selective IgA deficiency is increased in IDDM, we have screened a homogeneous series of adult patients with IDDM for selective IgA deficiency. One patient (1:261) was found to have a selective IgA deficiency. The prevalence of selective IgA deficiency among adult French blood donors is 1:1400. Thus, although IDDM and selective IgA deficiency are both associated with the presence of non-Asp amino acids at position 57 of the HLA DQ beta chain, the frequency of this immunodeficiency in adult IDDM patients is not significantly increased.
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PMID:The prevalence of selective IgA deficiency in type 1 diabetes mellitus. 152 Apr 83

The coeliac disease (CD) or gluten-sensitive enteropathy (GSE) is a permanent intolerance to wheat gliadin and to correlated proteins inducing malabsorption and typical damages of the jejunal mucosa (total or subtotal villous atrophy = SVA) in genetically-predisposed individuals ("DQW2"). A large amount of research has been devoted to CD pathogenesis: the most recent studies, thanks to sophisticated and experimental methods, support the pathogenetic immunological theory and the one of direct cytotoxicity. The correct diagnostic procedure for CD, established in 1970 by the European Society for Pediatric Gastroenterology and Nutrition (ESPGAN), suggested three small bowel mucosal biopsies. In the last years, because of the difficulties of such a practice, the necessity of non-invasive diagnostic approaches has developed; such approaches have been verified in absorption tests (one-hour blood xylose, intestinal permeability methods) and in immunogenetic tests (antibodies antigliadin, anti-reticulin, anti-endomysium, anti 90 KD glycoprotein, anti-human jejunum, HLA I/II antigens). The specific MHC antigens establish CD's incidence in several population and in particular situations, as in first-degree relatives and in diseases associated with CD (dermatitis herpetiformis (DH), insulin dependent diabetes mellitus (IDDM) and other auto-immune syndromes). The specific serum antibodies singly used as first level screening if estimated in combination with absorption tests, reach the highest levels of specificity and sensibility in CD diagnosis. It's anyway fundamental the comparison with at least a typical CD histological feature, caused by a challenge with a sufficient gluten to be carried in dubious cases and in non high auxological risk age (ESPGAN 1989). Adolescence is a period of frequent non compliance with a gluten-free diet and of particular psychological and physical problems: the apparent "gluten insensitivity", typical of teen-agers and adults, recalls the definitions of silent CD and latent CD (iceberg like). In the first case the jejunal mucosa is abnormal and the symptomatology isn't evident. In latent CD, genetically restricted, the mucosa is normal but there are minimal markers of inappropriate immunity to gliadin (at intestinal humoral immunity level) and a possible worsening of histological lesions to the third stage under environmental stimuli. This represents a two-stage model CD. That's why CD is still under-evaluated despite recent statistics reporting an increasing incidence (late and atypical forms). Prevalence rates between 1:300 and 1:4,000 and more are quoted in literature. The necessity of a strict gluten-free diet is confirmed by the evident frequency of lymphoma and by the increased risk of malignancy in untreated CD.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Celiac disease and its diagnostic evolution. Comparisons and experiences in a hospital pediatric department (1975-1992). I]. 152 93

In 27 children (15 males and 12 females) with insulin-dependent diabetes mellitus (IDDM), aged 1.2-13.5 years (mean 9.9 +/- 3.6 years) we investigated immunoglobulins (IgG, IgA, IgM), IgG subclass levels and islet-cell antibodies (ICA) at diagnosis and at 6 and 12 months after disease onset. At diagnosis, IgG levels were lower than -2SD in 7 patients (26%), IgA in 1 (3.7%), IgM in 1 (3.7%). IgG subclass levels were below the 3rd percentile in 13 patients (48.1%); in particular IgG1 in 7 (26%), IgG2 in 3 (11.1%), IgG3 in 2 and IgG4 undetectable in 1 case. In 3 out of the 13 patients combined IgG1-IgG3, IgG1-IgG2 and IgG1-IgG4-IgA deficiencies were observed. ICA were greater than 20 Juvenile Diabetes Foundation units in 17/27 patients. The HLA-DR2 frequency was higher in patients with IgG subclass deficiency than in patients with normal IgG subclass levels. During follow up, IgG levels normalized in 6 patients while IgA and IgM did not change. IgG1 normalized in 5 out of the 7 patients, IgG2 in all patients while IgG3 and IgG4 did not change. One year later ICA were still present in 8/27 patients. The hypogammaglobulinaemia and IgG subclass deficiencies observed in our patients could have either a genetic or an acquired basis.
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PMID:Transient IgG subclass deficiencies in newly diagnosed diabetic children. 160 Oct 8

Susceptibility to IDDM is strongly associated with HLA. Some HLA allelic combinations (haplotypes) can be found in most patients, whereas other haplotypes are encountered only rarely. It has been proposed that this difference in susceptibility depends on the absence (in the DR3 and DR4 haplotypes) or the presence (in the DR2 haplotype) of Asp57 in the DQ beta-chain. Data on southern European populations challenge this hypothesis because the DR2 haplotype has not been associated negatively with IDDM, as reported in northern European populations. This study on a selected panel of DR2-positive Italian IDDM patients shows that 19 of 21 (90.5%) DR2 haplotypes possess a non-Asp57 DQB allele. Moreover, the same non-Asp57 subtype has a comparatively high frequency (9/28, or 32.1%, DR2 haplotypes) also in the DR2-positive healthy Italian population. The difference between patients and control subjects is significant (P less than 0.0001). This is the largest series of DR2-positive patients analyzed so far. Comparison with cumulated data in various white populations shows a distinct northern European-to-southern European gradient. Toward southern Europe, the relative frequency of the non-Asp57 DR2 subtype increases. Concomitantly, the apparent protective effect of the DR2 haplotype disappears. Therefore, the observed differences in DR2-IDDM association in white populations can be explained adequately by the Asp57 hypothesis, which this study's data strongly support.
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PMID:An explanation for the neutral effect of DR2 on IDDM susceptibility in central Italy. 162 63

Type 1 diabetes seems to be an autoimmune disease in which T cells have a substantial role. A possible target antigen was suggested by the proliferation of CD4 T cells from a newly diagnosed patient in response to a 38 kD polypeptide of the insulin-secretory-granule membrane. To see whether this reactivity is widespread at disease onset, we have generated T-cell lines in vitro from peripheral blood mononuclear cells of nineteen children of caucasoid origin with newly diagnosed type 1 diabetes and sixteen healthy controls matched for age and HLA antigens. The procedure involved two cycles of incubation with a rat beta-cell tumour subcellular fraction enriched in secretory granules and plasma membrane components, followed by a proliferation assay. Fourteen (74% [95% confidence interval 49-91%]) of the patients' cell lines showed a positive proliferative response on subsequent exposure to the islet-cell antigen preparation compared with only two (13% [2-38%]) of the controls (p = 3 x 10(-4); difference 61% [44-87%]). Two subjects who had high titres of islet-cell autoantibodies (ICA) without clinical diabetes produced responsive T-cell lines. Reactivity towards the 38 kD fraction of insulin-secretory-granule membranes was found only in patients (eight of ten responders tested; 95% CI 44-98%) and one ICA-positive non-diabetic subject. Detection of an ongoing autoimmune T-cell response might be useful diagnostically and could lead to prevention of diabetes through specific immunotherapy.
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PMID:T-cell reactivity to 38 kD insulin-secretory-granule protein in patients with recent-onset type 1 diabetes. 167 18

There are three common C2 protein alleles in caucasians, C2*C, C2*B, and C2*Q0, with allele frequencies of 0.96, 0.03, and 0.01, as well as Sst I RFLP variants of 2.75, 2.7, 2.65, 2.55, and 2.4 kb, with frequencies of 0.017, 0.533, 0.358, 0.017, and 0.075. Thus, C2*C is informatively split by the RFLP. Of 94 nonrandomly ascertained caucasian complotypes, 77 contained C2*C, four contained C2*Q0, and 13 had C2*B. None of the C2*C-containing complotypes carried the 2.75 kb Sst I fragment and all of the complotypes with C2*B or C2*Q0 carried it. All of the C2*Q0 alleles were associated with C4A*4, C4B*2 in the complotype S042 as previously reported. C2*B was usually (9/13) in the complotype SB42, occasionally (1/13 each) in SB45, SB41, SB(4,3)0, and SB31. Thus, the association of the C2 2.75-kb fragment was with C2*B and C2*Q0, not with C4A*4, C4B*2, or even C4A*4 alone. The complotype SC42 was associated with the 2.65-kb Sst I fragment in four of five instances and in a single example with the 2.7-kb fragment. C2*B and C2*Q0 possibly had a common evolutionary ancestor complotype which carried the 2.75-kb Sst I fragment, and BF*S, C4A*4, and C4B*2. C2*B (particularly as the haplotype HLA-Bw62, SB42, DR4) is associated with type 1 diabetes but C2*Q0 is protective.
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PMID:A restriction fragment of the C2 gene is a unique marker for C2 deficiency and the uncommon C2 allele C2*B (a marker for type 1 diabetes). 168 65

T cell defined epitopes on class II HLA molecules (epitopes distinguishable by T cells but not by antibodies) seem to be important determinants of IDDM susceptibility/resistance. Although HLA-DR4 is associated with IDDM in many populations, DR4-positive HLA haplotypes vary greatly (relative risk from greater than 10 to less than 1). This variation seems to depend on both the DQ allele and T cell defined subtypes of the DR4 allele. These IDDM associated alleles at the two loci (DQB1 and DRB1) are not correlated with each other in the healthy population, so they clearly are independent risk factors. HLA-DR2 has universally been associated with lack of IDDM, and seems to be protective. However, not all DR2 haplotypes protect, and the protection or lack of protection correlates with T cell defined subtypes of DR2. In this case, however, the DR2 subtypes do correlate with DQ alleles, so it is unclear which locus (loci) is (are) actually affecting the disease process. It may be significant that, for both DR2 and DR4, only the more protective subtypes have arginine at amino acid position 71. Other portions of the DR beta chain are clearly important, however. Although TCR alpha and beta seemed to be promising candidates for additional IDDM susceptibility genes, in fact the various TCR alpha and beta haplotypes are equal, or nearly equal, with regard to IDDM susceptibility. The importance of HLA alleles in IDDM susceptibility, and the lack of importance of TCR alpha and beta alleles, may be due to the different means by which the HLA and TCR molecules achieve antigen binding diversity: HLA molecules by multiple loci and allelic diversity, and TCR molecules by the tremendous diversity that can be generated from a single TCR allele during T cell maturation.
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PMID:T cell defined HLA epitopes and T cell receptor polymorphism in insulin dependent diabetes mellitus. 171 35

HLA typing was done in 25 cases of insulin dependent diabetes mellitus (IDDM) and compared with 60 healthy controls. There was a significantly increased frequency of HLA B-8, HLA B-12 and HLA DR-3 in IDDMO. The odds ratio (relative risk) of developing IDDM for HLA B-8 was 4.42 (p less than 0.10), for HLA B-12 was 3.56 (p less than 0.10) and for HLA DR3 9.75 (p less than 0.001). There was no correlation of HLA specificity with complications of diabetes.
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PMID:Human leucocyte antigen and insulin dependent diabetes mellitus. 172 75

The allelic forms of the HLA-DQB gene have been recognized as susceptibility markers of type 1 diabetes mellitus. One of these alleles, the DQw3.2 (DQw8), accounts for the well-documented association of the DQw3 locus with the disease. This report describes a method using the polymerase chain reaction mismatch technique to amplify the three different DQw3 allele sequences in 26 insulin-dependent diabetic patients. Primers were designed that differed only at one base at the growing end of their sequences. Using a common oligonucleotide primer located downstream in the first domain of the DQB gene and three other primers located at the other end of the sequence being amplified, it was possible to identify and distinguish the DQw8 allele from the other two closely related alleles (DQw7, DQw9). This method, which could be useful in excluding HLA-related susceptibility to diabetes mellitus, is rapid and nonisotopic, and indeed could be adapted to investigate any DNA sequence polymorphism.
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PMID:Use of the polymerase chain reaction mismatch technique to identify the HLA-DQw8 allele in patients with insulin-dependent diabetes mellitus. 172 61


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