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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors report a case of a 41-year-old woman with diabetes and chronic renal failure in whom antihuman leukocyte antigen antibodies developed after she received a frozen bone allograft that limited her access to organ donors. The patient had a chondrosarcoma of the right distal femur. A wide resection with segmental total knee arthroplasty was followed by a revision using a composite bone allograft prosthesis. After revision, broadly reactive lymphocytotoxic antibodies developed in the patient. The patient's panel reactive antibody level rose from 28% to a peak of 70%. Panel reactive antibody expresses the percentage of a panel of human leukocyte antigen type T lymphocytes from 40 individuals (representative of all human leukocyte antigen Class I histocompatibility antigens) to which antihuman leukocyte antigen Class I lymphocytotoxic antibodies have developed in the recipient as measured by the antiglobulin crossmatch method. The specificity of the patient's primary antibody is found in 45% of donors available in Illinois since 1988 (N = 1606). Because a positive crossmatch precludes kidney and pancreas transplantation, at least 45% of cadaver organ donors were excluded from use for this patient. This is an unusual case that focuses on the potential impact of bone allografts in patients who may need subsequent organ transplantation.
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PMID:Bone allografts are immunogenic and may preclude subsequent organ transplants. 922 59

Some non-insulin-dependent diabetes mellitus (NIDDM) patients are positive for antibodies to glutamic acid decarboxylase (anti-GAD), and they tend to develop insulin deficiency. The aim of this study was to evaluate the prevalence of anti-GAD in NIDDM with secondary failure of sulfonylurea agents (NIDDM-SF) and to investigate the diagnostic significance of seropositivity for anti-GAD in NIDDM-SF patients by evaluating human leukocyte antigen (HLA)-DRB1 alleles concurrently. The prevalence of anti-GAD in NIDDM-SF, NIDDM, and new-onset (within 1 year after onset) insulin-dependent diabetes mellitus (IDDM) was 9.3% (39/420), 3.1% (12/392), and 65.0% (13/20), respectively. Pancreatic beta cell function deteriorated in NIDDM-SF patients positive for anti-GAD. HLA-DRB1 allele typing revealed that NIDDM-SF patients positive for anti-GAD were significantly associated with DRB1*0901 (RR = 2.81, P < 0.01), which is one of the susceptible alleles to IDDM. Shorter interval before development of secondary failure and insulin deficiency were significantly associated with the presence of DRB1*0901 (P < 0.05) in NIDDM-SF patients positive for anti-GAD. In conclusion, nearly 10% of NIDDM-SF patients are positive for anti-GAD, suggesting that an autoimmune mechanism might play an important role in the pathogenesis of NIDDM-SF patients. In addition, a combination of serological marker (anti-GAD) and genetic marker (HLA-DRB1) is useful for predicting clinical course of NIDDM patients with secondary failure of sulfonylurea agents.
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PMID:Diagnostic significance of antibodies to glutamic acid decarboxylase in Japanese diabetic patients with secondary oral hypoglycemic agents failure. 934 1

The impact of matching for the human leukocyte antigen (HLA)-DQ phenotype in cadaveric renal transplantation is unclear. We analyzed the effect of matching serologically defined HLA-DQ phenotypes on renal allograft survival in 12,050 first cadaveric renal transplants (recipients were 63.5% white and 36.5% African-American). Recipients were entered into the South-Eastern Organ Procurement Foundation (SEOPF) database between 1 October 1987 and 6 June 1995. A series of life table analyses were done to test the equality of survival curves for HLA-DQ match, both alone and accommodating for differences in recipient race and HLA-DR match. Cox regression models were then performed to detect differences in allograft survival based upon HLA-DQ match. Initial adjustments were done by recipient race. Subsequent adjustments were done by recipient and donor race, age and sex, cold ischemia time (CIT), body mass index (BMI), cyclosporine A (CyA) use, peak panel reactive antibody (PRA) titer, year of transplant, presence of diabetes mellitus (DM), and degree of HLA-A,B and HLA-DR match as covariates. The effect of varying degrees of HLA-DQ match on graft survival were similar between the two races (p = 0.87). In all recipients, an 8.3% reduction in graft failure was observed for each increase in HLA-DQ match using the Cox regression model adjusted only for recipient race (p = 0.004). A non-significant 3.0% reduction in graft failure (p = 0.38) was observed for each level of increasing HLA-DQ match when using the Cox regression model adjusted for recipient and donor race, age and sex, CIT, BMI, CyA use, year of transplant, DM, HLA-A,B and -DR match. In this model, superior HLA-A,B match and HLA-DR match, recipient and donor age, male donor sex, shorter CIT, white race of recipient, lower peak PRA, CyA use, and absence of DM significantly improved graft survival (all < or = 0.004). We conclude that HLA-DQ matching does not significantly affect cadaveric renal allograft survival once adjusted for other known predictors of graft outcome.
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PMID:HLA-DQ matching in cadaveric renal transplantation. 936 45

Endocrine autoimmune disorders share susceptibility and resistance factors of the human leukocyte antigen system on the short arm of chromosome 6, but other gene loci also contribute to predisposition and protection. Because the cytotoxic T lymphocyte antigen 4 (CTLA4) alanine-17 encoded by the CTLA4 gene on chromosome 2q33 confers susceptibility to Graves' disease, as well as to type 1 (insulin-dependent) diabetes mellitus, we investigated this dimorphism in the other endocrine autoimmune disorders: Hashimoto's thyroiditis and Addison's disease. We analyzed the CTLA4 exon 1 polymorphism (49 A/G) in 73 patients with Hashimoto's thyroiditis, 76 with Addison's disease, and 466 healthy controls. This dimorphism corresponds to an aminoacid exchange (Thr/Ala) in the leader peptide of the expressed protein. CTLA4 alleles were defined by PCR, single-strand conformational polymorphism analysis, and restriction fragment length polymorphism analysis using BbvI. Patients with Hashimoto's thyroiditis had significantly more Ala alleles than controls, both as homozygotes (22% vs. 15%) and heterozygotes (53% vs. 46%), and less Thr than controls as homozygotes (25% vs. 39%), P < 0.04. The phenotypic frequency for Ala was significantly higher in patients (75%), compared with controls (61%), P < 0.03. Patients with Addison's disease did not differ significantly from controls, but those carrying the suceptibility marker, human leukocyte antigen DQA1*0501, were significantly more CTLA4 Ala17 positive than controls with the same DQA1 allele (P < 0.05). In conclusion, an alanine at codon 17 of CTLA4 confers genetic susceptibility to Hashimoto's thyroiditis, whereas this applies only to the subgroup of DQA1*0501+ patients with Addison's disease.
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PMID:Codon 17 polymorphism of the cytotoxic T lymphocyte antigen 4 gene in Hashimoto's thyroiditis and Addison's disease. 939 26

New protective or disease-associated polymorphisms in the TAP1 gene were sought in insulin-dependent diabetes mellitus (IDDM) patients with the use of denaturing gradient gel electrophoresis (DGGE) screening of genomic DNA. The TAP1 gene is located in the human leukocyte antigen (HLA) class II region of the genome and encodes components of a peptide transporter essential for antigen presentation by HLA class I molecules. Fragments of TAP1 corresponding to the 5' promoter, each of the 11 exons (with portions of adjacent intronic regions) and the 3' flanking region were amplified by the polymerase chain reaction and then subjected to DGGE. DNA fragments of TAP1 yielded DGGE bands with patterns whose frequencies differed between IDDM patients and controls. Specific DGGE band patterns with fragments corresponding to the promoter, exons or introns 3, 6, 7, 8, 9 or 10 of TAP1 were detected exclusively in either patients or controls. Sequencing of TAP1 fragments encompassing exon 7 gave rise to a DGGE band pattern exclusively observed in an IDDM patient and sequencing revealed a previously unidentified polymorphisms at codon 518 (GTC-->ATC, Val-->Ile). Another unique polymorphism uncovered by DGGE revealed by sequencing a polymorphism in intron 2 in a diabetic patient. The genotypes of additional HLA class II matched patients and controls were determined with regard to five exonic and one intronic TAP1 polymorphism. A 10 base pair intronic insertion in intron 9 was exclusively identified in controls and missing from patients (P = 0.017). Further large population-based studies may reveal whether these newly identified at risk or protective TAP1 variants confer markers of statistical risk in diverse population groups.
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PMID:Screening of the TAP1 gene by denaturing gradient gel electrophoresis in insulin-dependent diabetes mellitus: detection and comparison of new polymorphisms between patients and controls. 945 10

To better define prevailing activation of circulating T cell subsets in insulin-dependent diabetes mellitus (IDDM) of recent onset (DM; n = 31; median age +/- SD, 28 +/- 6.9 yr) and of long standing (DML; n = 27; age, 33 +/- 10.4 yr; median duration of disease, 105 months), CD4+ and CD8+ T cells were analyzed to determine their naive and memory subsets as well as their expression of human leukocyte antigen (HLA)-DR, interleukin-2 receptor alpha-chain (CD25), and CD69 by three-color flow cytometry. Twenty-six healthy subjects (HS; age, 32.0 +/- 8.2 yr) served as controls. No deviation was seen in either IDDM group compared to HS in CD25 expression on CD4+ or CD8+ cells or in their CD45RA+ or CD45RA- subsets. HLA-DR expression, however, was increased (P < 0.05) in total CD8+ cells and CD45RA+ cells, with CD45RA- CD8+ cells joining the prevailing pattern only in DML. Among CD4+ cells, increased expression of HLA-DR molecules was restricted to total and CD45RA- cells in DML. CD69 expression did not differ between IDDM and HS, but differed between DML (CD4+, CD8+, and CD45RA- CD4+) and DM only. In conclusion, our data demonstrate that HLA-DR expression in IDDM is restricted to memory cells (CD45RA-) among CD4+ cells in DML and is more markedly confined to naive (CD45RA+) than to memory CD8+ cells, whereas the early activation antigen CD69 is more readily expressed in DML than in DM. The observed activation of circulating T cells suggests an ongoing immune process in IDDM both at clinical manifestation and after long duration.
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PMID:Increased CD69 and human leukocyte antigen-DR expression on T lymphocytes in insulin-dependent diabetes mellitus of long standing. 962 61

Accurate classification of diabetes in some young patients is difficult but clearly of importance in deciding the appropriate treatment. We report the different clinical courses and beta-cell function changes in 2 young-onset diabetics. In the beginning, each of them was considered to be a patient with insulin-dependent diabetes mellitus (IDDM) and was treated with insulin. Then, treatment was shifted from insulin to oral hypoglycemic agents (OHA) because each patient's beta-cell function was comparable to that of patients with non-insulin-dependent diabetes mellitus (NIDDM). In case 1, the patient's glycemic control and beta-cell function progressively deteriorated and finally insulin therapy was required. In case 2, the patient was continuously treated with OHA. Although his blood glucose was not well-controlled, his beta-cell function had been well-preserved. Recently he achieved near-normoglycemia by improving his diet and OHA compliance. Clearly, case 1 was a slowly progressive Type 1 DM patient and case 2 was a young Type 2 DM patient. This classification was further supported by the finding that the patient in case 1 had human leukocyte antigen (HLA)-DR3, but the patient in case 2 did not.
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PMID:Clinical courses and changes of pancreatic beta-cell function in young-onset diabetics: report of two cases. 984 16

The human leukocyte antigen (HLA) complex, encompassing 3.5 Mb of DNA from the centromeric HLA-DPB2 locus to the telomeric HLA-F locus on chromosome 6p21, encodes a major part of the genetic predisposition to develop type 1 diabetes, designated "IDDM1." A primary role for allelic variation of the class II HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci has been established. However, studies of animals and humans have indicated that other, unmapped, major histocompatibility complex (MHC)-linked genes are participating in IDDM1. The strong linkage disequilibrium between genes in this complex makes mapping a difficult task. In the present paper, we report on the approach we have devised to circumvent the confounding effects of disequilibrium between class II alleles and alleles at other MHC loci. We have scanned 12 Mb of the MHC and flanking chromosome regions with microsatellite polymorphisms and analyzed the transmission of these marker alleles to diabetic probands from parents who were homozygous for the alleles of the HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes. Our analysis, using three independent family sets, suggests the presence of an additional type I diabetes gene (or genes). This approach is useful for the analysis of other loci linked to common diseases, to verify if a candidate polymorphism can explain all of the association of a region or if the association is due to two or more loci in linkage disequilibrium with each other.
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PMID:The predisposition to type 1 diabetes linked to the human leukocyte antigen complex includes at least one non-class II gene. 1073 75

Celiac disease is a permanent intolerance to ingested gluten that results in immunologically mediated inflammatory damage to the small-intestinal mucosa. Celiac disease is associated with both human leukocyte antigen (HLA) and non-HLA genes and with other immune disorders, notably juvenile diabetes and thyroid disease. The classic sprue syndrome of steatorrhea and malnutrition coupled with multiple deficiency states may be less common than more subtle and often monosymptomatic presentations of the disease. Diverse problems such as dental anomalies, short stature, osteopenic bone disease, lactose intolerance, infertility, and nonspecific abdominal pain among many others may be the only manifestations of celiac disease. The rate at which celiac disease is diagnosed depends on the level of suspicion for the disease. Although diagnosis relies on intestinal biopsy findings, serologic tests are useful as screening tools and as an adjunct to diagnosis. The treatment of celiac disease is lifelong avoidance of dietary gluten. Gluten-free diets are now readily achievable with appropriate professional instruction and community support. Both benign and malignant complications of celiac disease occur but these can often be avoided by early diagnosis and compliance with a gluten-free diet.
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PMID:The widening spectrum of celiac disease. 1007 17

The human leukocyte antigen (HLA)-DQA1*0102/DQB1*0602/DRB1*1501 (DR2) haplotype confers strong protection from type 1 diabetes. Growing evidence suggests that such protection may be mostly encoded by the DQB1*0602 allele, and we reported that even first degree relatives with islet cell antibodies (ICA) have an extremely low diabetes risk if they carry DQB1*0602. Recently, novel variants of the DQB1*0602 and *0603 alleles were reported in four patients with type 1 diabetes originally typed as DQB1*0602 with conventional techniques. One inference from this observation is that DQB1*0602 may confer absolute protection and may never occur in type 1 diabetes. By this hypothesis, all patients typed as DQB1*0602 positive with conventional techniques should carry one of the above diabetes-permissive variants instead of the protective DQB1*0602. Such variants could also occur in ICA/DQB1*0602-positive relatives, with the implication that their diabetes risk could be significantly higher than previously estimated. We therefore sequenced the DQB1*0602 and DQA1*0102 alleles in all ICA/DQB1*0602-positive relatives (n = 8) previously described and in six rare patients with type 1 diabetes and DQB1*0602. We found that all relatives and patients carry the known DQB1*0602 and DQA1*0102 sequences, and none of them has the mtDNA A3243G mutation associated with late-onset diabetes in ICA-positive individuals. These findings suggest that diabetes-permissive DQB1*0602/3 variants may be very rare. Thus, although the protective effect associated with DQB1*0602 is extremely powerful, it is not absolute. Nonetheless, the development of diabetes in individuals with DQB1*0602 remains extremely unlikely, even in the presence of ICA, as confirmed by our further evaluation of ICA/DQB1*0602-positive relatives, none of whom has yet developed diabetes.
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PMID:Sequence analysis of the diabetes-protective human leukocyte antigen-DQB1*0602 allele in unaffected, islet cell antibody-positive first degree relatives and in rare patients with type 1 diabetes. 1032 7


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