Wang Yao, Fei Yang
Department of Trauma and Orthopaedic, Ningbo No.2 Hospital, Ningbo, Zhejiang, China.
Department of Hematology and Oncology, Ningbo No.2 Hospital, Ningbo, Zhejiang, China.
Medicine (Baltimore). 2024 Dec 20;103(51):e40945. doi: 10.1097/MD.0000000000040945.
Myeloproliferative neoplasms (MPN) are chronic hematological disorders marked by the abnormal proliferation of bone marrow cells. The most commonly encountered forms are polycythemia vera (PV), primary myelofibrosis (PMF), and essential thrombocythemia (ET). These disorders are generally associated with increases in blood components, which can lead to conditions like splenomegaly, thrombosis, bleeding tendencies, and a heightened risk of progressing to acute leukemia. Previous research has indicated a possible link between immune cells and MPN, yet this association is still poorly understood. This study seeks to elucidate the causal relationship between immune cell characteristics and the development of MPN. In this study, we employed Mendelian randomization (MR) to investigate potential causal links between 731 immune cell traits and the risk of developing MPN, leveraging data from genome-wide association studies (GWAS). To ensure the robustness of our findings, we conducted extensive sensitivity analyses to assess heterogeneity and detect any pleiotropic effects. Moreover, we implemented a false discovery rate (FDR) correction to mitigate the risk of false positives that may result from the multiple hypothesis testing, thereby adjusting for any statistical biases due to multiple comparisons. The immune phenotype IgD on IgD+ CD24- B cells demonstrated a statistically significant protective effect against MPN (PFDR = 0.047). Upon adjusting the significance threshold to PFDR < 0.20, 16 immune cell phenotypes were significantly associated with MPN. Among these, 11 were found to exert a protective effect against MPN, 5 phenotypes were associated with an elevated risk of MPN. This research highlights a significant association between various immune cell phenotypes and the risk of developing MPN, thereby advancing our understanding of the intricate interplay between immune cell traits and the progression of MPN.
骨髓增殖性肿瘤（MPN）是一类慢性血液系统疾病，其特征为骨髓细胞异常增殖。最常见的类型是真性红细胞增多症（PV）、原发性骨髓纤维化（PMF）和原发性血小板增多症（ET）。这些疾病通常与血液成分增加有关，可导致脾肿大、血栓形成、出血倾向以及进展为急性白血病的风险增加。先前的研究表明免疫细胞与MPN之间可能存在联系，但这种关联仍未得到充分理解。本研究旨在阐明免疫细胞特征与MPN发生发展之间的因果关系。在本研究中，我们利用全基因组关联研究（GWAS）的数据，采用孟德尔随机化（MR）方法来研究731种免疫细胞特征与发生MPN风险之间的潜在因果联系。为确保研究结果的稳健性，我们进行了广泛的敏感性分析，以评估异质性并检测任何多效性效应。此外，我们实施了错误发现率（FDR）校正，以降低多重假设检验可能导致的假阳性风险，从而校正因多重比较引起的任何统计偏差。IgD + CD24 - B细胞上的免疫表型IgD对MPN具有统计学显著的保护作用（PFDR = 0.047）。将显著性阈值调整为PFDR < 0.20后，16种免疫细胞表型与MPN显著相关。其中，11种被发现对MPN具有保护作用，5种表型与MPN风险升高相关。本研究突出了各种免疫细胞表型与发生MPN风险之间的显著关联，从而增进了我们对免疫细胞特征与MPN进展之间复杂相互作用的理解。
