Introduction: In pancreatic islet transplantation, the exact contribution of human leukocyte antigen (HLA) matching to graft survival remains unclear. Islets may be exposed to allogenic rejection but also the recurrence of type 1 diabetes (T1D). We evaluated the HLA-DR matching, including the impact of diabetogenic HLA-DR3 or HLA-DR4 matches.
Methods: We retrospectively examined the HLA profile in 965 transplant recipients and 2327 islet donors. The study population was obtained from patients enrolled in the Collaborative Islet Transplant Registry. We then identified 87 recipients who received a single-islet infusion. Islet-kidney recipients, 2nd islet infusion, and patients with missing data were excluded from the analysis (n=878).
Results: HLA-DR3 and HLA-DR4 were present in 29.7% and 32.6% of T1D recipients and 11.6% and 15.8% of the donors, respectively. We identified 52 T1D islet recipients mismatched for HLA-DR (group A), 11 with 1 or 2 HLA-DR-matches but excluding HLA-DR3 and HLA- DR4 (group B), and 24 matched for HLA-DR3 or HLA-DR4 (group C). Insulin-independence was maintained in a significantly higher percentage of group B recipients from year one through five post-transplantation (p<0.01). At five-year post-transplantation, 78% of group B was insulin-independent compared to 24% (group A) and 35% (group C). Insulin-independence correlated with significantly better glycemic control (HbA1c <7%), fasting blood glucose, and reduced severe hypoglycemic events. Matching HLA-A-B-DR (≥3) independently of HLA- DR3 or HLA-DR4 matching did not improve graft survival.
Conclusion: This study suggests that matching HLA-DR but excluding the diabetogenic HLA-DR3 and/or 4 is a significant predictor for long-term islet survival.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070978 | PMC |
| http://dx.doi.org/10.3389/fimmu.2023.1110544 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Characteristics of autoantibody-positive individuals without high-risk HLA-DR4-DQ8 or HLA-DR3-DQ2 haplotypes.
Diabetologia
December 2024
University of Miami Miller School of Medicine, University of Miami, Miami, FL, USA.
Aims/hypothesis: Many studies of type 1 diabetes pathogenesis focus on individuals with high-risk HLA haplotypes. We tested the hypothesis that, among islet autoantibody-positive individuals, lacking HLA-DRB1*04-DQA1*03-DQB1*0302 (HLA-DR4-DQ8) and/or HLA-DRB1*0301-DQA1*0501-DQB1*0201 (HLA-DR3-DQ2) is associated with phenotypic differences, compared with those who have these high-risk HLA haplotypes.
Methods: We classified autoantibody-positive relatives of individuals with type 1 diabetes into four groups based on having both HLA-DR4-DQ8 and HLA-DR3-DQ2 (DR3/DR4; n=1263), HLA-DR4-DQ8 but not HLA-DR3-DQ2 (DR4/non-DR3; n=2340), HLA-DR3-DQ2 but not HLA-DR4-DQ8 (DR3/non-DR4; n=1607) and neither HLA-DR3-DQ2 nor HLA-DR4-DQ8 (DRX/DRX; n=1294).
Genetic Discovery and Risk Prediction for Type 1 Diabetes in Individuals Without High-Risk HLA-DR3/DR4 Haplotypes.
Diabetes Care
December 2024
Department of Pediatrics, University of California, San Diego, La Jolla, CA.
Article Synopsis
- The study investigates type 1 diabetes (T1D) in patients without high-risk HLA-DR3 or -DR4 haplotypes, identifying genetic factors and improving risk prediction for this group.
- Researchers analyzed data from 12,316 non-DR3/DR4 individuals, discovering 18 T1D risk variants that affect disease development differently based on HLA status and showing a greater polygenic burden for non-DR3/DR4 patients.
- A newly developed genetic risk score (GRS) significantly outperformed existing scores in predicting T1D for those without DR3/DR4, highlighting the need for tailored approaches in understanding and predicting the disease.
Genetics of C-peptide and Age at Diagnosis in Type 1 Diabetes.
Diabetes
November 2024
Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Identified genetic loci for C-peptide and age at diagnosis (AAD) in individuals with type 1 diabetes (T1D) explain only a small proportion of their variation. Here, we aimed to perform large metagenome-wide association studies (GWAS) of C-peptide and AAD in T1D; and to identify the HLA allele/haplotypes associated with C-peptide and AAD. 7,252 and 7,923 European individuals with T1D were included in C-peptide and AAD GWAS, respectively.
View Article and Find Full Text PDFRhupus syndrome: Description of 9 cases with special attention to the HLA-DR genotype.
Med Clin (Barc)
January 2025
Servicio de Reumatología, Hospital Universitario y Politécnico La Fe, Valencia, España.
Article Synopsis
- - Rhupus is a rare syndrome that combines symptoms of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), characterized by specific autoantibodies and erosive polyarthritis.
- - This study analyzed the HLA-DR genetic profiles of 9 patients diagnosed with rhupus, finding that it commonly occurs in women with early RA symptoms and noteworthy serological markers like ANA, RF, and anti-CCP.
- - Results indicated a higher prevalence of certain HLA-DR types (HLA-DR1 and DR9) in rhupus patients compared to those with RA or SLE, suggesting potential for early identification of rhupus before an overlap diagnosis is made. *
Article Synopsis
- This study investigates the link between whole exome sequencing (WES) data and clinical features in children diagnosed with type 1 diabetes before age 5, analyzing 99 unrelated cases.
- Of the participants, 8.1% had potentially harmful rare variants in MODY genes, which were associated with specific genetic risk factors and different clinical markers compared to those without these variants.
- The findings suggest that WES may help identify distinct subtypes (endotypes) of type 1 diabetes and pave the way for tailored treatments in young patients.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!