当前位置: X-MOL 学术HLA › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Development of an immunogenicity score for HLA‐DQ eplets: A conceptual study
HLA ( IF 5.9 ) Pub Date : 2020-10-17 , DOI: 10.1111/tan.14110
Lara Schawalder 1 , Gideon Hönger 1, 2, 3 , Marc Kleiser 3 , Michelle R van Heck 4 , Loes A L van de Pasch 4 , Sanne Vendelbosch 4 , Erik H Rozemuller 4 , Stefan Schaub 1, 2, 3
Affiliation  

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.

中文翻译:

HLA-DQ eplets免疫原性评分的发展:一项概念研究

片基被定义为HLA分子表面上独特的氨基酸构型。这项研究的目的是评估在HLA-DQ不匹配的221名孕妇中HLA-DQ eplets的免疫原性。我们通过针对它的抗体反应频率定义了一个小细胞的免疫原性。所有列出的DQB1或DQA1 eplets中约有90%至少错配了5倍,因此计入了其免疫原性的计算。免疫原性得分最高的五个的DQB1 eplets是55PP,52PR,52PQ,85VG和45EV;所有DQB1 eplets中有25%没有反应。免疫原性得分最高的五个的DQA1 eplets是25YS,47QL,55RR,187T和18S;所有DQA1 eplets中有17%没有反应。与各种分子失配得分(例如,小球失配载荷,氨基酸失配载荷)相比,免疫原性得分在曲线下面积更大,可以预测儿童特异性抗体的发育。基于HLA抗体反应模式,重叠的小片段被确定为明确分配免疫原性评分的障碍。在此概念研究中,我们探索了HLA-DQ eplets的免疫原性,并绘制了HLA-DQ分子上潜在免疫原性区域的图,这需要在临床移植队列中进行验证。
更新日期:2020-12-09
down
wechat
bug