2018年5月，我所吴德沛教授、吴小津副教授研究团队在JCI insight杂志以研究论文形式发表了关于脂质代谢物与移植后并发症的最新研究成果“。该研究系国际上首次报道硬脂酸/软脂酸在异基因造血干细胞移植后急性移植物抗宿主病（aGVHD）和复发中的作用。吴德沛教授该文的通讯作者。
越来越多研究 关注代谢异常与aGVHD的关系，因为代谢产物能够更准确地反映生物体系的状 态，是描述不同物种的复杂生命活动的通用语言，可能更加早期和准确的反映aGVHD发生的过程。脂质代谢异常与免疫系统关系密切，有报道高饱和脂肪酸饮食可以影响机体淋巴细胞的功能和数量，进而影响全身免疫。不饱和脂肪酸可能影响TLR受体表达，参与全身免疫反应。也有报道高脂肪酸饮食也会 影响IL-6的分泌，可能影响aGVHD的发生。脂质代谢产物种类很多，它们参与全身免疫过程具体机制不同，也不是很明确。
课题组采用非靶向代谢组手段对造血干细胞移植前后不同时间点的连续114名患者456份样本进行了非靶向的血清代谢物质分析，结果发现脂质代谢异常与造血干细胞移植后aGVHD发生关系密切。硬脂酸和软脂酸两个饱和脂肪酸在移植后aGVHD发病中出现差异性改变。硬脂酸酸和软脂酸比例越低，aGVHD发生率越高，并且复发越低，我们结合临床资料通过竞争风险模型分析发现，两者比例是aGVHD和复发的主要危险因素。通过验证模型，硬脂酸/软脂酸可以作为早期aGVHD的代谢生物学标志物。
原文摘要：
BACKGROUND.There are very few studies investigating metabolicbiomarkers to predict acute
graft-versus-host disease (aGVHD) after allogeneichematopoietic stem cell transplantation (HSCT).
Metabolic models can provide a framework for analyzingthe information-rich omics data sets in
this setting.
METHODS.Four hundred and fifty-six samples from one hundred andfourteen consecutive
patients who underwent HSCT from January 2012 to May 2014were collected for this study.
The changes in serum metabolite levels were investigatedusing a gas chromatography–mass
spectrometry–based metabolomics approach andunderwent statistical analysis.
RESULTS.Significant metabolic changes were observed on day 7. Thestearic acid/palmitic acid
(SA/PA) ratio was effective in the diagnosis of grade II–IV aGVHD.Multivariate analysis showed
that patients with high SA/PA ratios on day 7 after HSCTwere less likely to develop II–IV aGVHD
than patients with low SA/PA ratios (odds ratio [OR] =0.06, 95% CI 0.02–0.18,P< 0.001).After
the adjustment for clinical characteristics, the SA/PAratio had no significant effect on overall
survival (hazard ratio [HR] = 1.95, 95% CI 0.92–4.14,P= 0.08), and patients in the high SA/PA ratio
group were significantly more likely to relapse thanthose in the low ratio group (HR = 2.26, 95% CI
1.04–4.91,P= 0.04).
CONCLUSION.Our findings suggest that the SA/PA ratio on day 7 afterHSCT is an excellent
biomarker to predict both aGVHD and relapse. The serumSA/PA ratio measured on day 7 after
transplantation may improve risk stratification for aGVHDand relapse after allogeneic stem cell
transplantation.
