| 1. |
- Sedimbi, S. K., et al.
(författare)
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SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-21
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Tidskriftsartikel (refereegranskat)abstract
- SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.
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| 2. |
- Shin, J. H., et al.
(författare)
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IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
- 2007
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Ingår i: Genes Immun. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
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Tidskriftsartikel (refereegranskat)abstract
- In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.
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| 3. |
- Lindehammer, Sabina, et al.
(författare)
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Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk
- 2008
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 45:4, s. 231-5
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.
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| 4. |
- Sanjeevi, Carani B., et al.
(författare)
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The risk conferred by HLA-DR and DQ for type 1 diabetes in 0-35-year age group are different in different regions of Sweden
- 2008
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. - 9781573317337 ; 1150, s. 106-11
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Tidskriftsartikel (refereegranskat)abstract
- HLA DR4-DQ8 and DR3-DQ2 haplotypes account for 89% of newly diagnosed cases of type 1 diabetes (T1D) in Sweden. The presence of a single copy of DQ6 confers protection. The aim of the present study is to evaluate whether the risk conferred by high risk HLA DR and DQ to T1D is similar in all regions of Sweden and see whether there are any significant regional differences. The subjects comprised 799 consecutively diagnosed T1D patients and 585 age-, sex-, and geography-matched healthy controls in the age group 0-35 years. HLA typing for high-risk haplotypes was previously performed using PCR-SSOP and RFLP. The results showed that HLA DR3-DR4 gave an odds ratio of 8.14 for the whole of Sweden. However, when the study group was divided into six geographical regions, subjects from Stockholm had the highest OR, followed by those from Lund, Linköping, Gothenburg, Umeå, and Uppsala. Absolute protection was conferred by the presence of DQ6 in subjects from the Linköping region, but varied in the other regions. The frequency of DR3 and DQ2, DR4 and DQ8, DR15, and DQ6 in patients showed high linkage for each region, but were different between regions. In conclusion: The risk conferred by high-risk HLA varies in different regions for a homogenous population in Sweden. The results highlight the important role played by the various environmental factors in the precipitation of T1D.
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| 5. |
- Skogsberg, L., et al.
(författare)
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Improved treatment satisfaction but no difference in metabolic control when using continuous subcutaneous insulin infusion vs. multiple daily injections in children at onset of type 1 diabetes mellitus
- 2008
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-5448 .- 1399-543X. ; 9:5, s. 472-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to compare safety, metabolic control, and treatment satisfaction in children/adolescents at onset of type 1 diabetes mellitus who were treated with either continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). RESEARCH DESIGN AND METHODS: Seventy-two children/adolescents (7-17 yr of age) were enrolled in this open, randomized, parallel, multicenter study. Approximately half of the patients were treated with MDI (natural protamine hagedorn [NPH] insulin twice daily and rapid-acting insulin three to -four times daily, n = 38) by pen, and the other half received CSII (n = 34). The patients were followed for 24 months with clinical visits at the entry of the study and after 1, 6, 12, and 24 months. During these visits, hemoglobin A1c, insulin doses, weight, and height were registered. Severe episodes of hypoglycemia and ketoacidosis as well as technical problems were recorded. In addition, the patients/parents answered the Diabetes Treatment Satisfaction Questionnaire. RESULTS: There was no significant difference in metabolic control between the treatment groups. Treatment satisfaction was significantly higher in the group treated with CSII compared with the MDI group (p
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| 6. |
- Skogsberg, Ulrika, et al.
(författare)
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Adult ABO-incompatible liver transplantation, using A and B donors
- 2006
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Ingår i: Xenotransplantation. - 0908-665X. ; 13:2, s. 154-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The longer waiting time for a liver graft in patients with blood group O makes it necessary to expand the donor pool for these patients. This applies in both urgent situations and for elective patients. We report on our experience with ABO-incompatible liver transplantation using A2 and B non-secretor donors here. PATIENTS AND METHODS: Between 1996 and 2005, 12 adult blood group O recipients (seven male/five female) received ABO-incompatible cadaveric liver grafts (10 A2 donors, two B non-secretor donors). The indications were either rapid deterioration of liver function or hepatocellular cancer, in blood group O recipients, where an ABO-identical/compatible graft was not available. Mean recipient age was 54+/-8 (mean+/-SD) yr. All pre-operative CDC crossmatches were negative. The initial immunosuppression was induction therapy with antithymocyte globulin (n = 3), interleukin 2 receptor antagonists (n = 3) or anti-CD20 antibody (rituximab) (n = 1), followed by a tacrolimus-based protocol. Three patients underwent plasmapheresis post-transplantation. Baseline biopsies were taken before or immediately after reperfusion of the graft and after grafting when clinically indicated. No pre-operative plasmapheresis, immunoadsorption or splenectomies were performed. RESULTS: Patient and graft survival was 10/12 (83%) and 8/12 (67%), respectively, with a 6.5-month median follow-up (range 10 days to 109 months). Two patients (B non-secretor grafts) died of multiorgan failure probably because of a poor condition before transplantation. Three patients were retransplanted. Causes of graft loss were bacterial arteritis (n = 1), death with a functioning graft (n = 1) and portal vein thrombosis (n = 2). In one of the patients with portal vein thrombosis, an anti-A titer increase occurred concomitantly, and ABO incompatibility as the cause of the thrombosis cannot be excluded. Seven acute rejections occurred in five patients and all were reversed by steroids or increased tacrolimus dosage. The pre-transplant anti-A titers tested against A1 red blood cells were 1 to 128 (NaCl technique) and 4 to 1024 (indirect antiglobulin technique, IAT); the maximum postoperative titers were 16 to 2048 (NaCl) and 256 to 32,000 (IAT). CONCLUSION: The favorable outcome of A2 to O grafting, with a patient survival of 10/10 and a graft survival of 8/10, makes it possible to also consider this blood group combination in non-urgent situations. The use of non-secretor donor grafts is interesting but has to be further documented. There was no hyperacute rejection or increased rate of rejection. Anti-A/B titer changes seem not to play a significant role in the monitoring of ABO-incompatible liver transplantation.
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| 7. |
- Skogsberg, Ulrika, et al.
(författare)
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Successful ABO-incompatible liver transplantation using A2 donors
- 2006
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Ingår i: Transplantation proceedings. - 0041-1345. ; 38:8, s. 2667-70
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The longer waiting time for a liver graft among patients with blood group O makes it necessary to expand the donor pool for these patients. We herein have reported our experience with ABO-incompatible liver transplantation using A(2) donors to blood group O recipients. PATIENTS AND METHODS: Between 1996 to 2005, 10 adult blood group O recipients received 10 A(2) cadaveric grafts. Mean recipient age was 52 +/- 7.7 years (mean +/- SD). The initial immunosuppression was induction with antithymocyte globulin (n = 2), interleukin-2-receptor antagonists (n = 3), or anti-CD20 antibody (rituximab, n = 1), followed by a tacrolimus-based protocol. No preoperative plasmapheresis, immunoadsorption, or splenectomies were performed. RESULTS: Patient and graft survival was 10/10 and 8/10, respectively, at 8.5 months median follow-up (range 10 days to 109 months). Two patients were retransplanted because of bacterial arteritis (n = 1) and portal vein thrombosis (n = 1). The six acute rejections, which occurred in four patients, were all reversed by steroids or increased tacrolimus dosages. The pretransplant anti-A titers against A(1) red blood cells were 1:128 (NaCl technique) and 1:8 to 1024 (IAT technique). The maximum postoperative titers were 1:64 to 4000 (NaCl) and 1:256 to 32000 (IAT). CONCLUSION: The favorable outcome of A(2) to O grafting, with a patient survival of 10/10 and graft survival of 8/10, makes it possible to consider this blood group combination also in nonurgent situations. There was no hyperacute rejection or increased rate of rejections. Anti-A/B titer changes seem to not play a significant role in the monitoring of A(2) to O liver transplantation.
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| 8. |
- Rydberg, L, et al.
(författare)
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ABO antigen expression in graft tissue: is titration against donor erythrocytes relevant?
- 2007
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337. ; 84:12 Suppl
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Tidskriftsartikel (refereegranskat)abstract
- ABO-incompatible living donor renal transplantation has become an accepted treatment for end-stage renal disease. Two main factors appear to be important when crossing the ABO barrier, the donor organ A/B antigen expression and the amount of recipient anti-A/B antibody. Antigen expression depends on the ABO blood group and subgroup and may vary in different tissues and cells. The amount of recipient anti-A/B antibody, determined by titration, is very variable. One major drawback with titration is the lack of conformity between different laboratories, making comparisons difficult. For clinical use, the anti-A/B antibody titration technique has to be simple, rapid, and cheap, in addition to being accurate. Although there is a need for more standardized procedures for determination of ABO antibodies, existing techniques are sufficient in the clinical care of patients. To illustrate the variation in susceptibility of different graft tissues to ABO antibodies, in this paper we describe a case of an ABO-incompatible combined liver and kidney transplantation.
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