| 1. |
- Alshiekh, Shehab, et al.
(författare)
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High-resolution genotyping indicates that children with type 1 diabetes and celiac disease share three HLA class II loci in DRB3, DRB4 and DRB5 genes
- 2021
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Ingår i: HLA: Immune Response Genetics. - : Wiley. - 2059-2302. ; 97:1, s. 44-51
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes (T1D) and celiac disease (CD) share common genetic loci, mainly within the human leukocyte antigen (HLA) class II complex. Extended genotyping of HLA class II alleles and their potential risk for developing both diseases remains to be studied. The present study compared extended HLA-class II gene polymorphisms in children with T1D, CD, and a subgroup diagnosed with both diseases (T1D w/CD). Next-generation targeted sequencing (NGTS) of HLA-DRB3, DRB4, DRB5, DRB1, DQA1, DQB1, DPA1, and DPB1 alleles from DNA collected from 68 T1D, 219 CD, and seven T1D w/CD patients were compared with 636 HLA-genotyped Swedish children from the general population selected as controls. In comparison to controls, the DRB4*01:03:01 allele occurred more frequently in T1D w/CD (odds ratio (OR) = 7.84; 95% confidence interval (95% CI) = (2.24, 34.5), P = 0.0002) and T1D (OR = 3.86; 95% CI, (2.69, 5.55), P = 1.07 × 10−14), respectively. The DRB3*01:01:02 allele occurred more frequently in CD as compared to controls (OR = 7.87; 95% CI, (6.17, 10.03), P = 4.24 × 10−71), but less frequently in T1D (OR = 2.59; 95% CI, (1.76, 3.81), P = 7.29 × 10−07) and T1D w/CD (OR = 0.87; 95% CI, (0.09, 3.96), P ≤ 0.999). The frequency of the DRB4*01:03:01-DRB1*04:01:01-DQA1*03:01:01-DQB1*03:02:01 (DR4-DQ8) haplotype was higher in T1D w/CD (OR = 12.88; 95% CI (4.35, 38.14) P = 3.75 × 10−9), and moderately higher in T1D (OR = 2.13; 95% CI (1.18, 3.83) P = 0.01) compared with controls, but comparable in CD (OR = 1.45; 95% CI (0.94, 2.21), P = 0.08) and controls. Children with T1D and CD are associated with DRB4*01:03:01, DRB3*01:01:02, and DRB3*02:02:01 of which DRB4*01:03:01 confers the strongest risk allele for developing T1D w/CD.
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| 2. |
- Alshiekh, Shehab, et al.
(författare)
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High-resolution genotyping of HLA class I loci in children with type 1 diabetes and celiac disease
- 2021
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Ingår i: HLA: Immune Response Genetics. - : Wiley. - 2059-2302. ; 97:6, s. 505-511
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: HLA-DQ2 and DQ8 contribute to the strongest risk haplotypes for type 1 diabetes (T1D) and celiac disease (CD). The variation in genetic risk association is likely linked to different HLA class II loci susceptibility, but association studies of HLA class I alleles are scarce. The aim was to investigate HLA class I A, B, and C alleles polymorphisms in children with only T1D, CD, and a subgroup with both T1D and CD (T1D w/CD). Materials and methods: HLA class I A, B, and C genes were genotyped using next-generation targeted sequencing. A conditional analysis was performed on 68 children with T1D, 219 children with CD and seven children with T1D w/CD enrolled from a birth cohort study at high genetic risk children from the South of Sweden. Results: Among 1764 HLA class I allele variants, A*29:02:01 in T1D w/CD was associated with both T1D (OR = 21.42 [1.05, 1322.4], p = 0.0231) and CD (OR = 35 [2.36, 529.12], p = 0.0051) along with C*05:01:01 with both T1D (OR = 5.54 [1.06, 24.8], p = 0.02) and CD (OR = 6.84 [1.46, 26.01], p = 0.0077). No independent effects of HLA-B allele associations were observed in T1D w/CD. Conclusion: Although the distribution of HLA class I alleles differs between children with T1D and CD, the A*29:02:01 and C*05:01:01 alleles showed shared risk association of both diseases.
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| 3. |
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| 4. |
- Gudeta, Adugna N., et al.
(författare)
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Distribution of HLA-DQ risk genotypes for celiac disease in Ethiopian children
- 2020
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Ingår i: HLA: Immune Response Genetics. - : Wiley. - 2059-2302. ; 96:6, s. 681-687
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Tidskriftsartikel (refereegranskat)abstract
- Most patients with celiac disease are positive for either HLA-DQA1*05:01-DQB1*02 (DQ2.5) or DQA1*03:01-DQB1*03:02 (DQ8). Remaining few patients are usually DQA1*02:01-DQB1*02 (DQ2.2) carriers. Screenings of populations with high frequencies of these HLA-DQA1-DQB1 haplotypes report a 1% to 3% celiac disease prevalence. The aim was to determine the prevalence of HLA-DQ risk haplotypes for celiac disease in Ethiopian children. Dried blood spots collected from 1193 children from the Oromia regional state of Ethiopia were genotyped for HLA-DQA1 and DQB1 genotyping using an asymmetric polymerase chain reaction (PCR) and a subsequent hybridization of allele-specific probes. As references, 2000 previously HLA-genotyped children randomly selected from the general population in Sweden were included. DQ2.2 was the most common haplotype and found in 15.3% of Ethiopian children, which was higher compared with 6.7% of Swedish references (P <.0001). Opposed to this finding, DQ2.5 and DQ8 occurred in 9.7% and 6.8% of Ethiopian children, which were less frequent compared with 12.8% and 13.1% of Swedish references, respectively (P <.0001). The DQ2.5-trans genotype encoded by DQA1*05-DQB1*03:01 in combination with DQ2.2 occurred in 3.6% of Ethiopian children, which was higher compared with 1.3% of Swedish references (P <.0001). However, when children with moderate high to very high-risk HLA genotypes were grouped together, there was no difference between Ethiopian children and Swedish references (27.4% vs 29.0%) (P =.3504). The frequency of HLA risk haplotypes for celiac disease is very similar in Ethiopian and Swedish children. This finding of importance will be useful in future screening of children for celiac disease in Ethiopia.
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| 6. |
- Hurley, Carolyn K., et al.
(författare)
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Common, intermediate and well-documented HLA alleles in world populations : CIWD version 3.0.0
- 2020
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Ingår i: HLA. - : WILEY. - 2059-2302 .- 2059-2310. ; 95:6, s. 516-531
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Tidskriftsartikel (refereegranskat)abstract
- A catalog of common, intermediate and well-documented (CIWD) HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQB1 and -DPB1 alleles has been compiled from over 8 million individuals using data from 20 unrelated hematopoietic stem cell volunteer donor registries. Individuals are divided into seven geographic/ancestral/ethnic groups and data are summarized for each group and for the total population. P (two-field) and G group assignments are divided into one of four frequency categories: common (>= 1 in 10 000), intermediate (>= 1 in 100 000), well-documented (>= 5 occurrences) or not-CIWD. Overall 26% of alleles in IPD-IMGT/HLA version 3.31.0 at P group resolution fall into the three CIWD categories. The two-field catalog includes 18% (n = 545) common, 17% (n = 513) intermediate, and 65% (n = 1997) well-documented alleles. Full-field allele frequency data are provided but are limited in value by the variations in resolution used by the registries. A recommended CIWD list is based on the most frequent category in the total or any of the seven geographic/ancestral/ethnic groups. Data are also provided so users can compile a catalog specific to the population groups that they serve. Comparisons are made to three previous CWD reports representing more limited population groups. This catalog, CIWD version 3.0.0, is a step closer to the collection of global HLA frequencies and to a clearer view of HLA diversity in the human population as a whole.
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| 7. |
- Kaprio, Tuomas, et al.
(författare)
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Human leukocyte antigen-G expression correlates with histological grade but not with prognosis in colorectal carcinoma
- 2021
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Ingår i: HLA. - : John Wiley & Sons. - 2059-2302 .- 2059-2310. ; 98:3, s. 213-217
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Tidskriftsartikel (refereegranskat)abstract
- Trophoblast-specific expression of human leukocyte antigen-G (HLA-G) induces immune tolerance for the developing fetus. Pathological HLA-G expression later in life might contribute to immune escape of various cancers. We studied the still controversial role of HLA-G in colorectal carcinoma (CRC) using the MEM-G/1 antibody and a tissue microarray series of CRC tumors (n = 317). HLA-G expression appeared in 20% of the tumors and showed high intratumoral heterogeneity. HLA-G positivity was associated with better differentiation (p = 0.002) and non-mucinous histology (p = 0.008). However, HLA-G expression alone showed no prognostic value: 5-years disease-specific survival among patients with HLA-G expression was 68.9% (95% CI: 62.7%-75.0%) compared to 74.8% (95% CI: 63.2%-86.3%) among those without expression. These results support a modulatory role of HLA-G in CRC.
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| 8. |
- Koefoed-Nielsen, P., et al.
(författare)
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Scandiatransplant acceptable mismatch program (STAMP) a bridge to transplanting highly immunized patients
- 2017
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Ingår i: HLA. - : Wiley. - 2059-2302 .- 2059-2310. ; 90:1, s. 17-24
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Tidskriftsartikel (refereegranskat)abstract
- Background: Highly immunized patients are a challenge for organ transplantation programs. One way of increasing the likelihood of transplantation in this group of patients is to expand the possible donations by defining acceptable HLA mismatches. In the Scandiatransplant Acceptable Mismatch Program (STAMP), a decentralized approach has been implemented in 2009. Aims: The program has been improved during the years from utilizing HLA-A, -B, -DR matching only to include typing of all deceased donors for HLA-A, -B, -C, -DRB1 and -DQB1. The calculation of a transplantability score (TS) has been introduced in order to take both HLA and AB0 into consideration resulting in a more realistic picture of the transplantability chance. Materials and Methods: Patients were selected for eligibility and results of immunisation status were prepared in each of the 9 tissue typing laboratories, while access to the program is finally governed by a common steering group of immunologists and clinicians. Results: In the period from March 2009 until February 2015, 96 patients were transplanted within this program. The mean recipient age was 49 years and 57% were females, 30% of the patients were first transplants and of these 93% were females. The majority of the patients had 2-5 HLA-A, -B. -DR mismatches. The allograft survival at 60 months was 79.1%. Applying the TS to the cohort confirmed that patients with a low TS score had longer waiting times. Conclusion: The program has matured during the years and now proves to be a valid approach for transplanting highly immunized patients.
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| 9. |
- Sörman, Anna, 1981-, et al.
(författare)
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Identification of the novel HLA-B*08:181 allele in a volunteer donor for hematopoietic stem cells
- 2019
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Ingår i: HLA. - : Wiley. - 2059-2302 .- 2059-2310. ; 93:6, s. 485-486
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- HLA-B*08:181 differs from HLA-B*08:01:01:01 in codon 94, 95, 97 and 99 of exon 3.In this report, the HLA‐B*08:181 allele, will be described. The novel allele was found in a potential unrelated donor for hematopoietic stem cells. Currently, there are 5590 alleles described according to the IPD‐IMGT/HLA Database1 for the HLA‐B locus.During routine HLA typing of a potential unrelated bone marrow donor, the initial results obtained from Sanger sequencing (SBTengine, GenDX, Utrecht, The Netherlands) of the HLA‐B locus exons 2 to 4, suggested the presence of HLA B*07:227 and B*08:01:01. By testing with polymerase chain reaction ‐ single specific primer (PCR‐SSP) (Olerup, Stockholm, Sweden) this was not confirmed, instead the presence of the common B*07:02:01 together with a B*08:09/08:12 was suggested, thus indicating the possible presence of a novel HLA allele. To verify the finding, the sample was run on the PacBio long‐range platform (PacBio, Menlo Park, California). DNA was extracted from whole blood with the EZ1 DNA Blood kit (Qiagen, Hilden, Germany). The HLA‐B locus was amplified with B locus specific primers from the 5′ to 3′UTR and the end repair and ligation reaction were performed with the SMRTbell Barcoded Adapter Prep Kit (PacBio). Genotyping was performed using PacBio RSII (PacBio) and the resulting data was analyzed using NGSengine (GenDX). The result gave the clear result of B*07:02:01, the same results as previously, but the software gave the suggestion of HLA B*08:129, with three mismatches in exon 3. Consequently, the new allele shared the beginning of exon three with B*07:227, that is also found in B*57 alleles, thus explaining the Sanger sequencing. Comparison of the genomic full‐length sequence of B*08:129 and B*08:181 showed three nucleotide substitutions in codon 97 (A➔G and G➔T, AGG➔GTG) and 99 (C➔T, TAC➔TAT) in exon 3 (Figure 1). The substitution in codon 97 results in an exchange of Arginine to Valine while the nucleotide exchange in codon 99 does not result in any exchange of amino acid (aa). The chemical differences in the aa substitution from an electrically charged aa to a hydrophobic aa in the peptide binding area of the HLA protein would be considered to affect the protein function, that is, residue 97 is facing pockets C and E in the peptide binding groove.2 However, the serological typing of the potential donor showed a clear HLA B7 and B8 phenotype. Figure 1Sequence alignment of exon 3 of HLA‐B*08:01:01:01, HLA‐B*08:129 and HLA‐B*08:181. Dashes (−) indicate nucleotide identity. Codons are indicated by the numbers at the topThe extended HLA typing of the donor was A*01:01:01, 03:01:01; B*07:02:01G, 08:181; C*07:02:01, 07:01:01; DRB1*03:01:01, 15:01:01; DRB3*01:01:02; DRB5*01:01:01, DQA1*05:01:01, 01:02:01; DQB1*02:01:01, 06:02:01; DPA1*01:03:01, 02:01:02; DPB1*01:01:01, 04:01:01.The genomic sequence of B*08:181 has been submitted to GenBank and the IPD IMGT/HLA Databases (LT707070, HWS10027733).The name HLA‐B*08:181 has been officially assigned by the World Health Organization (WHO) Nomenclature Committee in April 2017. This follows the agreed policy that subject to the conditions are identified.3 Lists of such new names will be published in the following WHO Nomenclature Report.
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| 10. |
- Alshiekh, S., et al.
(författare)
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Different DRB1*03:01-DQB1*02:01 haplotypes confer different risk for celiac disease
- 2017
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Ingår i: Hla. - : Wiley. - 2059-2302. ; 90:2, s. 95-101
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Tidskriftsartikel (refereegranskat)abstract
- Celiac disease is associated with the HLA-DR3-DQA1*05:01-DQB1*02:01 and DR4-DQA1*03:01-DQB1*03:02 haplotypes. In addition, there are currently over 40 non-HLA loci associated with celiac disease. This study extends previous analyses on different HLA haplotypes in celiac disease using next generation targeted sequencing. Included were 143 patients with celiac disease and 135 non-celiac disease controls investigated at median 9.8 years (1.4-18.3 years). PCR-based amplification of HLA and sequencing with Illumina MiSeq technology were used for extended sequencing of the HLA class II haplotypes HLA-DRB1, DRB3, DRB4, DRB5, DQA1 and DQB1, respectively. Odds ratios were computed marginally for every allele and haplotype as the ratio of allelic frequency in patients and controls as ratio of exposure rates (RR), when comparing a null reference with equal exposure rates in cases and controls. Among the extended HLA haplotypes, the strongest risk haplotype for celiac disease was shown for DRB3*01:01:02 in linkage with DQA1*05:01-DQB1*02:01 (RR = 6.34; P-value < .0001). In a subpopulation analysis, DRB3*01:01:02-DQA1*05:01-DQB1*02:01 remained the most significant in patients with Scandinavian ethnicity (RR = 4.63; P < .0001) whereas DRB1*07:01:01-DRB4*01:03:01-DQA1*02:01-DQB1*02:02:01 presented the highest risk of celiac disease among non-Scandinavians (RR = 7.94; P = .011). The data also revealed 2 distinct celiac disease risk DR3-DQA1*05:01-DQB*02:01 haplotypes distinguished by either the DRB3*01:01:02 or DRB3*02:02:01 alleles, indicating that different DRB1*03:01-DQB1*02:01 haplotypes confer different risk for celiac disease. The associated risk of celiac disease for DR3-DRB3*01:01:02-DQA1*05:01-DQB1*02:01 is predominant among patients of Scandinavian ethnicity.
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| 19. |
- Svendsen, Signe Goul, et al.
(författare)
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Extended HLA-G haplotypes in patients with age-related macular degeneration
- 2018
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Ingår i: HLA: Immune Response Genetics. - : Wiley. - 2059-2302. ; 92:2, s. 83-89
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Tidskriftsartikel (refereegranskat)abstract
- The study aims to determine if genetic polymorphisms in the human leukocyte antigen (HLA)-G gene are associated with age-related macular degeneration (AMD). HLA-G is important for immunological tolerance, and it is also known to have angiogenic effects. Polymorphisms in the 5'-upstream regulatory region (URR) and 3'-untranslated region (UTR) of HLA-G have been associated with a number of diseases, especially with respect to a 14 bp insertion/deletion (ins/del) polymorphism in the 3'UTR. Full gene sequencing was performed on a cohort of 146 AMD patients and 63 healthy controls aged 60 years or older and HLA-G haplotypes were determined. Analyses were performed on a publicly available gene expression dataset from the NCBI GEO database (accession number GSE29801) from which expression data for HLA-G, -C and -A were extracted. Analysis of the GEO dataset showed that both HLA-G and -C was expressed in the back of the eye and that expression was upregulated in the macular area of AMD. No differences were observed between patients and controls when analysing the distribution of haplotypes in the HLA-G promoter, coding region, 3'UTR or the 14 bp ins/del polymorphism of the 3'UTR. The increased expression of HLA-G in the macula of AMD patients indicates a role of HLA-G in the micro environment as part of the AMD pathogenesis. This is supported by the expression of HLA-C, which has previously been shown to play a role in AMD. The HLA-G haplotype distribution did not display any differences between AMD patients and controls. This article is protected by copyright. All rights reserved.
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