Gamberini Maria Rita, Zuccato Cristina, Zurlo Matteo, Cosenza Lucia Carmela, Finotti Alessia, Gambari Roberto
Center "Chiara Gemmo and Elio Zago" for the Research on Thalassemia, Università degli Studi di Ferrara, 44121 Ferrara, Italy.
Unità Operativa Interdipartimentale di Day Hospital della Talassemia e delle Emoglobinopatie, Arcispedale S. Anna di Ferrara, 44124 Ferrara, Italy.
Hematol Rep. 2023 Jul 12;15(3):432-439. doi: 10.3390/hematolrep15030044.
The β-thalassemias are a group of monogenic hereditary hematological disorders caused by deletions and/or mutations of the β-globin gene, leading to low or absent production of adult hemoglobin (HbA). For β-thalassemia, sirolimus has been under clinical consideration in two trials (NCT03877809 and NCT04247750). A reduced immune response to anti-SARS-CoV-2 vaccination has been reported in organ recipient patients treated with the immunosuppressant sirolimus. Therefore, there was some concern regarding the fact that monotherapy with sirolimus would reduce the antibody response after SARS-CoV-2 vaccination. In the representative clinical case reported in this study, sirolimus treatment induced the expected increase of fetal hemoglobin (HbF) but did not prevent the production of anti-SARS-CoV-2 IgG after vaccination with mRNA-1273 (Moderna). In our opinion, this case report should stimulate further studies on β-thalassemia patients under sirolimus monotherapy in order to confirm the safety (or even the positive effects) of sirolimus with respect to the humoral response to anti-SARS-CoV-2 vaccination. In addition, considering the extensive use of sirolimus for the treatment of other human pathologies (for instance, in organ transplantation, systemic lupus erythematosus, autoimmune cytopenia, and lymphangioleiomyomatosis), this case report study might be of general interest, as large numbers of patients are currently under sirolimus treatment.
β地中海贫血是一组由β珠蛋白基因缺失和/或突变引起的单基因遗传性血液疾病，导致成人血红蛋白（HbA）生成减少或缺乏。对于β地中海贫血，西罗莫司已在两项试验（NCT03877809和NCT04247750）中接受临床研究。据报道，接受免疫抑制剂西罗莫司治疗的器官移植受者患者对抗SARS-CoV-2疫苗的免疫反应降低。因此，有人担心西罗莫司单药治疗会降低SARS-CoV-2疫苗接种后的抗体反应。在本研究报告的代表性临床病例中，西罗莫司治疗导致胎儿血红蛋白（HbF）预期增加，但并未阻止接种mRNA-1273（Moderna）疫苗后抗SARS-CoV-2 IgG的产生。我们认为，该病例报告应促使对接受西罗莫司单药治疗的β地中海贫血患者进行进一步研究，以确认西罗莫司在抗SARS-CoV-2疫苗体液反应方面的安全性（甚至积极效果）。此外，考虑到西罗莫司在治疗其他人类疾病（例如器官移植、系统性红斑狼疮、自身免疫性血细胞减少症和淋巴管平滑肌瘤病）中的广泛应用，该病例报告研究可能具有普遍意义，因为目前有大量患者正在接受西罗莫司治疗。
