Li Ziping, Zhang Fujing, Jin Xianghong, Zhuang Junling
Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Beijing, 100730, China.
J Transl Med. 2025 Jan 26;23(1):117. doi: 10.1186/s12967-025-06140-y.
Immunotherapy is a significant risk factor for severe COVID-19 in multiple myeloma (MM) patients. Understanding how immunotherapies lead to severe COVID-19 is crucial for improving patient outcomes.
Human protein microarrays were used to examine the expression of 440 protein molecules in MM patients treated with bispecific T-cell engagers (BiTe) (n = 9), anti-CD38 monoclonal antibodies (mAbs) (n = 10), and proteasome inhibitor (PI)-based regimens (n = 10). Differentially expressed proteins (DEPs) were identified and analyzed using bioinformatics.
BiTe therapy was associated with a higher incidence of severe COVID-19. We identified 21 and 29 DEPs between BiTe and anti-CD38 mAbs group, and BiTe and PI-based group, respectively, along with 25 DEPs between the anti-CD38 and PI groups. Principal component analysis and clustering showed distinct protein expression profiles between the BiTe and PI groups. Gene Ontology (GO) analysis revealed that DEPs between the BiTe and PI groups were related to cytokine activity and leukocyte migration. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEPs were enriched in cytokine-cytokine receptor interaction and JAK-STAT signaling pathways. Leukemia inhibitory factor (LIF) is the most correlated with other DEPs and thus may play a key role in both enriched pathways, and the level of LIF protein was highest in the BiTe group.
BiTe therapy is linked to a higher risk of severe COVID-19 due to an inflammatory cytokine storm, with LIF and the JAK-STAT pathway playing key roles. Targeting LIF and JAK-STAT pathway may help reduce severe COVID-19 in MM patients treated with BiTe.
免疫疗法是多发性骨髓瘤（MM）患者发生重症 COVID-19 的重要危险因素。了解免疫疗法如何导致重症 COVID-19 对于改善患者预后至关重要。
使用人蛋白质微阵列检测接受双特异性 T 细胞衔接器（BiTe）治疗的 MM 患者（n = 9）、抗 CD38 单克隆抗体（mAb）治疗的患者（n = 10）和基于蛋白酶体抑制剂（PI）方案治疗的患者（n = 10）中 440 种蛋白质分子的表达。使用生物信息学方法鉴定和分析差异表达蛋白（DEP）。
BiTe 疗法与重症 COVID-19 的较高发病率相关。我们分别在 BiTe 与抗 CD38 mAb 组、BiTe 与基于 PI 的组之间鉴定出 21 种和 29 种 DEP，同时在抗 CD38 与 PI 组之间鉴定出 25 种 DEP。主成分分析和聚类显示 BiTe 组与 PI 组之间有明显不同的蛋白质表达谱。基因本体（GO）分析显示，BiTe 组与 PI 组之间的 DEP 与细胞因子活性和白细胞迁移有关。京都基因与基因组百科全书（KEGG）分析表明，这些 DEP 在细胞因子 - 细胞因子受体相互作用和 JAK-STAT 信号通路中富集。白血病抑制因子（LIF）与其他 DEP 的相关性最高，因此可能在这两个富集通路中起关键作用，且 LIF 蛋白水平在 BiTe 组中最高。
由于炎症细胞因子风暴，BiTe 疗法与重症 COVID-19 的较高风险相关，LIF 和 JAK-STAT 通路起关键作用。靶向 LIF 和 JAK-STAT 通路可能有助于降低接受 BiTe 治疗的 MM 患者发生重症 COVID-19 的风险。
