Department of Blood Transfusion, Fujita Health University Hospital, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192, Japan.
Department of Cellular and Molecular Biology, Fujita Health University School of Medical Sciences, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192, Japan.
Ann Hematol. 2022 Sep;101(9):1959-1969. doi: 10.1007/s00277-022-04921-9. Epub 2022 Jul 14.
SARS-CoV-2 infection has been reported to be associated with a positive direct antiglobulin test (DAT). In this study, an analysis of 40 consecutive coronavirus disease 2019 (COVID-19) cases from December 2020 to September 2021 in Japan revealed that patients of 70 years and over were predisposed to a positive DAT. DAT positivity was related to a decrease in the hemoglobin level. Anemia in DAT-positive COVID-19 patients was attributed to hemolysis, which was corroborated by high reticulocyte counts and an increase in the red blood cell distribution width. Human leukocyte antigen (HLA)-DRB112:01 and DRB112:02 were exclusively found in DAT-positive COVID-19 patients. In silico assays for the Spike protein of SARS-CoV-2 predicted several common core peptides that met the criteria for a B cell epitope and strong binding to both HLA-DRB112:01 and DRB112:02. Among these peptides, the amino acids sequence TSNFR, which is found within the S1 subunit of SARS-CoV-2 Spike protein, is shared by human blood group antigen Rhesus (Rh) CE polypeptides. In vitro analysis showed that the expression of HLA-DR in CD4 T cells and CD8 T cells from a DAT-positive patient was increased after pulsation with TSNFR-sequence-containing peptides. In summary, positive DAT is related to enhanced anemia and to HLA-DR12 in the Japanese population. A peptide sequence within SARS-CoV-2 Spike protein may act as an epitope for IgG binding to RBCs in DAT-positive COVID-19 patients.
据报道，SARS-CoV-2 感染与直接抗球蛋白试验（DAT）阳性有关。在这项研究中，分析了 2020 年 12 月至 2021 年 9 月在日本的 40 例连续冠状病毒病 2019（COVID-19）病例，结果显示 70 岁及以上的患者易发生 DAT 阳性。DAT 阳性与血红蛋白水平下降有关。DAT 阳性 COVID-19 患者的贫血归因于溶血，这得到高网织红细胞计数和红细胞分布宽度增加的证实。人类白细胞抗原（HLA）-DRB112:01 和 DRB112:02 仅在 DAT 阳性 COVID-19 患者中发现。对 SARS-CoV-2 的 Spike 蛋白进行的计算机模拟分析预测了几个常见的核心肽段，这些肽段符合 B 细胞表位的标准，并与 HLA-DRB112:01 和 DRB112:02 强烈结合。在这些肽段中，TSNFR 氨基酸序列存在于 SARS-CoV-2 Spike 蛋白的 S1 亚基中，与人类血型抗原 Rh 阴性（Ce）多肽共享。体外分析显示，与 DAT 阳性患者的 CD4 T 细胞和 CD8 T 细胞共培养时，用包含 TSNFR 序列的肽段脉冲处理后，HLA-DR 的表达增加。综上所述，DAT 阳性与增强的贫血和日本人群中的 HLA-DR12 相关。SARS-CoV-2 Spike 蛋白内的一个肽段可能作为 DAT 阳性 COVID-19 患者 IgG 与 RBC 结合的表位。
