Laboratory of Clinical Immunology, Department of Biomedicine, University Hospital Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland.
Haematologica. 2010 Aug;95(8):1389-96. doi: 10.3324/haematol.2009.017863. Epub 2010 Apr 23.
Life-threatening infections are a major cause of death after allogeneic stem cell transplantation. Complement Mannose-binding lectin is a key component of innate immunity. Functional deficiency of mannose-binding lectin due to genetic polymorphism is frequent. Previous reports showed conflicting results with respect to the influence of functional mannose-binding lectin deficiency on infectious risk after allogeneic stem cell transplantation. The aim of this study was to clarify the impact of low mannose-binding lectin levels on infectious risk in a unique cohort of very long-term survivors after stem cell transplantation.
Incidence of major infections was evaluable in 43 out of 44 very long-term survivors (over ten years) and studied retrospectively in relation to mannose-binding lectin serum concentrations.
Recipients with mannose-binding lectin levels below 1,000 ng/mL were at increased risk to suffer from one or more major infections (P=0.002) during entire follow up. Infectious susceptibility was increased after neutrophil recovery, particularly until 24 months (Hazard Ratio 3.4) with sustained effects afterwards (Hazard Ratio 2.9). Mannose-binding lectin serum concentrations below 1,000 ng/mL were independently associated with major infections after neutrophil recovery (P=0.009). In subgroup analyses occurrence of severe herpes virus infections in particular was associated with significantly lower mannose-binding lectin levels (P=0.02).
Our findings indicate that low mannose-binding lectin levels may predict markedly increased susceptibility to severe infections with sustained effects even late after allogeneic stem cell transplantation. Determinations of mannose-binding lectin status should therefore be included into pre-transplantation risk assessment.
危及生命的感染是异基因干细胞移植后死亡的主要原因。补体甘露聚糖结合凝集素是先天免疫的关键组成部分。由于遗传多态性,甘露聚糖结合凝集素的功能缺陷很常见。先前的报告显示,功能性甘露聚糖结合凝集素缺乏对异基因干细胞移植后感染风险的影响存在矛盾的结果。本研究的目的是在干细胞移植后非常长期存活者的独特队列中阐明低甘露聚糖结合凝集素水平对感染风险的影响。
在 44 名非常长期幸存者(超过十年)中的 43 名中评估了主要感染的发生率,并回顾性地研究了与甘露聚糖结合凝集素血清浓度的关系。
甘露聚糖结合凝集素水平低于 1000ng/ml 的受者在整个随访期间发生 1 次或多次主要感染的风险增加(P=0.002)。感染易感性在中性粒细胞恢复后增加,特别是在 24 个月内(危险比 3.4),随后持续存在(危险比 2.9)。中性粒细胞恢复后,甘露聚糖结合凝集素血清浓度低于 1000ng/ml 与主要感染独立相关(P=0.009)。亚组分析表明,严重疱疹病毒感染的发生与甘露聚糖结合凝集素水平显著降低有关(P=0.02)。
我们的发现表明,低甘露聚糖结合凝集素水平可能预示着严重感染的易感性显著增加,即使在异基因干细胞移植后晚期也持续存在。因此,在移植前风险评估中应包括甘露聚糖结合凝集素状态的测定。