Development of an immunogenicity score for HLA‐DQ eplets: A conceptual study
| Autor: | Lara Schawalder, Marc Kleiser, Michelle van Heck, Sanne Vendelbosch, Gideon Hönger, Stefan Schaub, Erik H. Rozemuller, Loes A. van de Pasch |
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| Rok vydání: | 2020 |
| Předmět: |
Immunology
chemical and pharmacologic phenomena immunogenicity complex mixtures Antibodies HLA-DQ alpha-Chains Conceptual study Hla molecules Pregnancy HLA-DQ Antigens HLA-DQ Genetics HLA-DQ beta-Chains Humans Immunology and Allergy Hla antibodies Alleles eplets biology Immunogenicity Original Articles HLA‐DQ Antibody response biology.protein Original Article Female Antibody |
| Zdroj: | Hla |
| ISSN: | 2059-2310 2059-2302 |
| DOI: | 10.1111/tan.14110 |
| Popis: | Eplets are defined as distinct amino acid configurations on the surface of HLA molecules. The aim of this study was to estimate the immunogenicity of HLA-DQ eplets in a cohort of 221 pregnancies with HLA-DQ mismatches. We defined the immunogenicity of an eplet by the frequency of antibody responses against it. Around 90% of all listed DQB1 or DQA1 eplets were at least five times mismatched and thus included for the calculation of their immunogenicity. The DQB1 eplets with the five highest immunogenicity scores were 55PP, 52PR, 52PQ, 85VG and 45EV; 25% of all DQB1 eplets were not reacting. The DQA1 eplets with the five highest immunogenicity scores were 25YS, 47QL, 55RR, 187T and 18S; 17% of all DQA1 eplets were not reacting. The immunogenicity score had a slightly higher area under the curve to predict development of child-specific antibodies than various molecular mismatch scores (eg, eplet mismatch load, amino acid mismatch load). Overlapping eplets were identified as a barrier to unambiguously assign the immunogenicity score based on HLA antibody reaction patterns. In this conceptual study, we explored the immunogenicity of HLA-DQ eplets and created a map of potentially immunogenic regions on HLA-DQ molecules, which requires validation in clinical transplant cohorts. |
| Databáze: | OpenAIRE |
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