Screening novel autoantigens targeted by serum IgG autoantibodies in immunorelated pancytopenia by SEREX
Screening novel autoantigens targeted by serum IgG autoantibodies in immunorelated pancytopenia by SEREX
复制标题
通过 SEREX 筛选免疫相关全血细胞减少症血清 IgG 自身抗体靶向的新型自身抗原
DOI：
10.1007/s12185-017-2287-0
复制
发表时间：
2017-11-01
影响因子：
2.1
通讯作者：
Shao, Zonghong
中科院分区：
文献类型：
--
作者：
Hao, Shanfeng;Fu, Rong;Shao, Zonghong
免疫相关性全血细胞减少症（IRP）的特征是由自身抗体介导的骨髓破坏或抑制所导致的全血细胞减少。然而，IRP中自身抗体所针对的自身抗原仍不明确。在本研究中，我们通过对重组cDNA表达文库进行血清学分析来筛选IRP中的新型自身抗原，并通过免疫印迹法比较了IRP患者和正常对照之间抗泛醌 - 细胞色素c还原酶复合物III亚基X（UQCR10）抗体水平。我们的结果表明，我们成功构建了K562 cDNA文库，并用其筛选出了在IRP造血细胞中表达的七种候选自身抗原：铁蛋白轻链多肽、泛醌 - 细胞色素c还原酶、泛醌 - 细胞色素c还原酶复合物III亚基X（UQCR10）、多功能甲基转移酶亚基TRM112样蛋白异构体1（TRMT112）、血红蛋白γ - G、癌蛋白18（又称微管不稳定蛋白，STMN1）转录变体3、磷酸甘油酸激酶1（PGK1）以及运输蛋白颗粒复合物亚基4（TRAPPC4）。17例IRP患者中有6例（35.29%）对UQCR10抗原呈阳性反应，而10例正常对照中仅有1例（10%）对UQCR10抗原有反应。对UQCR10抗原呈阳性反应的IRP患者与呈阴性反应的患者相比，总有效率（6/6）显著提高（阴性反应患者为5/11）。因此，UQCR10可能是参与IRP发生发展的自身抗原之一。
Immunorelated pancytopenia (IRP) is characterized by pancytopenia caused by autoantibody-mediated destruction or suppression of bone marrow. However, the autoantigens targeted by autoantibodies in IRP remain unclear. In the present study, we screened novel autoantigens in IRP by serological analysis of recombinant cDNA expression libraries and compared anti-UQCR10 antibody levels between IRP and normal controls detected by immunoblotting. Our results indicate that we successfully constructed the K562 cDNA library, which we used to screen seven candidate autoantigens expressed in haematopoietic cells of IRP: ferritin, light polypeptide, ubiquinol-cytochromecreductase, complex III subunit X (UQCR10), multifunctional methyl-transferase subunit TRM112-like protein isoform 1 (TRMT112), hemoglobin gamma-G, stathmin 1 (STMN1), transcript variant 3, phosphoglycerate kinase 1 (PGK1), and trafficking protein particle complex subunit 4 (TRAPPC4). Six of 17 (35.29%) IRP patients exhibited positive reactivity to UQCR10 antigen, while only one of 10 (10%) of normal controls reacted to UQCR10 antigen. The IRP patients with positive reactivity to UQCR10 antigen exhibited significantly improved total efficiency (6/6) compared with those with negative reactivity (5/11). Thus, UQCR10 may be implicated as one of the autoantigens involved in development of IRP.