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Anti-COX-2 autoantibody is a novel biomarker of immune aplastic anemia
Leukemia ( IF 11.4 ) Pub Date : 2022-08-05 , DOI: 10.1038/s41375-022-01654-6
Tiina Kelkka 1, 2 , Mikko Tyster 1, 2 , Sofie Lundgren 1, 2 , Xingmin Feng 3 , Cassandra Kerr 4 , Kohei Hosokawa 5 , Jani Huuhtanen 1, 2 , Mikko Keränen 1, 2 , Bhavisha Patel 3 , Toru Kawakami 6 , Yuka Maeda 7 , Otso Nieminen 1, 2 , Tiina Kasanen 1, 2 , Pasi Aronen 8 , Bhagwan Yadav 1, 2 , Hanna Rajala 1, 2 , Hideyuki Nakazawa 9 , Taina Jaatinen 10 , Eva Hellström-Lindberg 11 , Seishi Ogawa 12 , Fumihiro Ishida 13 , Hiroyoshi Nishikawa 7 , Shinji Nakao 5 , Jaroslaw Maciejewski 4 , Neal S Young 3 , Satu Mustjoki 1, 2, 14
Affiliation  

In immune aplastic anemia (IAA), severe pancytopenia results from the immune-mediated destruction of hematopoietic stem cells. Several autoantibodies have been reported, but no clinically applicable autoantibody tests are available for IAA. We screened autoantibodies using a microarray containing >9000 proteins and validated the findings in a large international cohort of IAA patients (n = 405) and controls (n = 815). We identified a novel autoantibody that binds to the C-terminal end of cyclooxygenase 2 (COX-2, aCOX-2 Ab). In total, 37% of all adult IAA patients tested positive for aCOX-2 Ab, while only 1.7% of the controls were aCOX-2 Ab positive. Sporadic non-IAA aCOX-2 Ab positive cases were observed among patients with related bone marrow failure diseases, multiple sclerosis, and type I diabetes, whereas no aCOX-2 Ab seropositivity was detected in the healthy controls, in patients with non-autoinflammatory diseases or rheumatoid arthritis. In IAA, anti-COX-2 Ab positivity correlated with age and the HLA-DRB1*15:01 genotype. 83% of the >40 years old IAA patients with HLA-DRB1*15:01 were anti-COX-2 Ab positive, indicating an excellent sensitivity in this group. aCOX-2 Ab positive IAA patients also presented lower platelet counts. Our results suggest that aCOX-2 Ab defines a distinct subgroup of IAA and may serve as a valuable disease biomarker.



中文翻译:

抗 COX-2 自身抗体是免疫性再生障碍性贫血的新型生物标志物

在免疫再生障碍性贫血 (IAA) 中,严重的全血细胞减少症是由免疫介导的造血干细胞破坏引起的。已经报道了几种自身抗体,但没有临床适用的自身抗体测试可用于 IAA。我们使用包含 >9000 种蛋白质的微阵列筛选自身抗体,并在 IAA 患者(n  = 405)和对照(n = 815)。我们鉴定了一种新的自身抗体,它与环氧合酶 2 的 C 末端结合(COX-2,aCOX-2 Ab)。总共有 37% 的成年 IAA 患者 aCOX-2 Ab 检测呈阳性,而只有 1.7% 的对照组呈 aCOX-2 Ab 阳性。在患有相关骨髓衰竭疾病、多发性硬化症和 I 型糖尿病的患者中观察到零星的非 IAA aCOX-2 Ab 阳性病例,而在非自身炎症性疾病患者的健康对照中未检测到 aCOX-2 Ab 血清阳性或类风湿性关节炎。在 IAA 中,抗 COX-2 抗体阳性与年龄和 HLA-DRB1*15:01 基因型相关。HLA-DRB1*15:01 的 >40 岁 IAA 患者中有 83% 为抗 COX-2 抗体阳性,表明该组具有极好的敏感性。aCOX-2 Ab 阳性 IAA 患者的血小板计数也较低。

更新日期:2022-08-05
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