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Contemporary analysis of functional immune recovery to opportunistic and vaccine-preventable infections after allogeneic haemopoietic stem cell transplantation.
Clinical & Translational Immunology ( IF 4.6 ) Pub Date : 2018-10-05 , DOI: 10.1002/cti2.1040
Harini D de Silva 1, 2, 3 , Rosemary A Ffrench 1, 4 , Maya Korem 2, 5 , Eva Orlowski 1 , David J Curtis 6, 7 , Andrew Spencer 6, 7 , Sharon Avery 7 , Sushrut Patil 7 , Catherine Orla Morrissey 2, 7
Affiliation  

OBJECTIVES Infections are a major cause of mortality after allogeneic haemopoietic stem cell transplantation (alloHSCT), and immune recovery is necessary for prevention. Novel transplant procedures have changed the epidemiology of infections but contemporary data on functional immune recovery are limited. In this pilot study, we aimed to measure immune recovery in the current era of alloHSCT. METHODS Twenty, 13, 11, 9 and 9 alloHSCT recipients had blood collected at baseline (time of conditioning) and 3-, 6-, 9-, and 12-months post-alloHSCT, respectively. Clinical data were collected, and immune recovery was measured using immunophenotyping, lymphocyte proliferation, cytokine analysis and antibody isotyping. RESULTS Median absolute T- and B-cell counts were below normal from baseline until 9- to 12-months post-alloHSCT. Median absolute CD4+ T-cell counts recovered at 12-months post-alloHSCT. Positive proliferative responses to Aspergillus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), influenza and tetanus antigens were detected from 9 months. IL-6 was the most abundant cytokine in cell cultures. In cultures stimulated with CMV, EBV, influenza and tetanus peptides, the CD4+ T-cell count correlated with IL-1β (P = 0.045) and CD8+ T-cell count with IFNγ (P = 0.013) and IL-1β (P = 0.012). The NK-cell count correlated with IL-1β (P = 0.02) and IL-17a (P = 0.03). Median serum levels of IgG1, IgG2 and IgG3 were normal while IgG4 and IgA were below normal range throughout follow-up. CONCLUSIONS This pilot study demonstrates that immune recovery can be measured using CD4+ T-cell counts, in vitro antigen stimulation and selected cytokines (IFNγ, IL-1β, IL-4, IL-6, IL-17, IL-21, IL-31) in alloHSCT recipients. While larger studies are required, monitoring immune recovery may have utility in predicting infection risk post-alloHSCT.

中文翻译:

同种异体造血干细胞移植后机会性和疫苗可预防感染的功能性免疫恢复的当代分析。

目的 感染是异基因造血干细胞移植 (alloHSCT) 后死亡的主要原因,免疫恢复是预防的必要条件。新的移植程序改变了感染的流行病学,但有关功能性免疫恢复的当代数据有限。在这项试点研究中,我们旨在测量当前 alloHSCT 时代的免疫恢复情况。方法 20、13、11、9 和 9 名 alloHSCT 受者分别在基线(调理时间)和 3、6、9 和 12 个月后收集血液。收集临床数据,并使用免疫表型、淋巴细胞增殖、细胞因子分析和抗体同种型测量免疫恢复。结果 从基线到 alloHSCT 后 9 至 12 个月,中位绝对 T 细胞和 B 细胞计数低于正常值。在 alloHSCT 后 12 个月恢复中位绝对 CD4+ T 细胞计数。从 9 个月开始检测到对曲霉、巨细胞病毒 (CMV)、爱泼斯坦-巴尔病毒 (EBV)、流感和破伤风抗原的阳性增殖反应。IL-6 是细胞培养物中最丰富的细胞因子。在用 CMV、EBV、流感和破伤风肽刺激的培养物中,CD4+ T 细胞计数与 IL-1β (P = 0.045) 相关,CD8+ T 细胞计数与 IFNγ (P = 0.013) 和 IL-1β (P = 0.012) 相关)。NK 细胞计数与 IL-1β (P = 0.02) 和 IL-17a (P = 0.03) 相关。IgG1、IgG2 和 IgG3 的中位血清水平正常,而 IgG4 和 IgA 在整个随访期间均低于正常范围。结论 该初步研究表明,可以使用 CD4+ T 细胞计数、体外抗原刺激和选择的细胞因子(IFNγ、IL-1β、IL-4、IL-6、IL-17、IL-21、IL-31)在 alloHSCT 受者中。虽然需要进行更大规模的研究,但监测免疫恢复可能有助于预测 alloHSCT 后的感染风险。
更新日期:2019-11-01
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