Liefeldt Lutz, Glander Petra, Klotsche Jens, Straub-Hohenbleicher Henriette, Budde Klemens, Eberspächer Bettina, Friedersdorff Frank, Halleck Fabian, Hambach Pia, Hofmann Jörg, Koch Nadine, Schmidt Danilo, Schrezenmeier Eva, Seelow Evelyn, Weber Ulrike, Zukunft Bianca, Eckardt Kai-Uwe, Choi Mira, Bachmann Friederike, Waiser Johannes
Department of Nephrology and Medical Intensive Care, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.
German Rheumatism Research Center Berlin-A Leibniz Institute, 10117 Berlin, Germany.
J Clin Med. 2022 Mar 18;11(6):1697. doi: 10.3390/jcm11061697.
Immunosuppression increases the risk of severe coronavirus disease 2019 (COVID-19). Morbidity and mortality of this disease in kidney transplant patients are higher than in the general population. As the vaccination response of transplant patients is weak, serological monitoring was performed. In this cohort study, we analyzed the determinants of vaccination response. All patients had no history of COVID-19. With anti-spike IgG monitoring, 148 responders and 415 non-responders were identified. We compared both groups using multivariate analyses of the cohort and a sub-cohort of mycophenolic-acid-treated patients. We investigated the influence of patient characteristics, immunosuppression, and erythrocyte inosine monophosphate dehydrogenase (IMPDH) activity. In responders, the time after transplantation was longer (13.5 vs. 8.5 years), the glomerular filtration rate was higher (56.9 vs. 47.8 mL/min/1.73 m2), and responders were younger (53.0 vs. 57.4 years). Heterologous vaccination was more effective than homologous vaccination. Calcineurin inhibitors plus mycophenolate reduced the seroconversion rate. No seroconversion was observed in belatacept patients. In mycophenolate-treated patients, IMPDH activity was a significantly better predictor of response than mycophenolate dose (AUC 0.84 vs. 0.62, p < 0.001). Immunosuppression strongly affects vaccine response. Modifications to immunosuppression should be considered in order to facilitate this response. Erythrocyte IMPDH activity can be used to guide mycophenolate treatment.
免疫抑制会增加重症2019冠状病毒病（COVID-19）的风险。该疾病在肾移植患者中的发病率和死亡率高于普通人群。由于移植患者的疫苗接种反应较弱，因此进行了血清学监测。在这项队列研究中，我们分析了疫苗接种反应的决定因素。所有患者均无COVID-19病史。通过抗刺突IgG监测，确定了148名有反应者和415名无反应者。我们使用队列的多变量分析以及霉酚酸治疗患者的亚队列对两组进行了比较。我们研究了患者特征、免疫抑制和红细胞肌苷单磷酸脱氢酶（IMPDH）活性的影响。在有反应者中，移植后的时间更长（13.5年对8.5年），肾小球滤过率更高（56.9对47.8 mL/min/1.73 m2），且有反应者更年轻（53.0岁对57.4岁）。异源疫苗接种比同源疫苗接种更有效。钙调神经磷酸酶抑制剂加霉酚酸降低了血清转化率。在贝拉西普治疗的患者中未观察到血清转化。在霉酚酸治疗的患者中，IMPDH活性比霉酚酸剂量更能显著预测反应（AUC 0.84对0.62，p < 0.001）。免疫抑制强烈影响疫苗反应。应考虑调整免疫抑制措施以促进这种反应。红细胞IMPDH活性可用于指导霉酚酸治疗。
