期刊
FRONTIERS IN IMMUNOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.01646
关键词
hematopoietic stem cell transplantation; insulin-like growth factor-1; single nucleotide polymorphisms; toxicity; systemic inflammation
类别
资金
- Research Council at Rigshospitalet
- Childhood Cancer Foundation [2017-1997]
Allogeneic hematopoietic stem cell transplantation (HSCT) is challenged by significant toxicities that are propagated by systemic inflammation caused by cytotoxic damage. Insulin-like growth factor-1 (IGF-1) is key in repair of most tissues and is to a large extent genetically determined. We investigated eight single nucleotide polymorphisms (SNPs) in the genes encoding IGF-1 and its binding protein (IGFBP3) in 543 patients undergoing HSCT to access their impact on systemic inflammation and clinical outcomes. Overall, median serum levels of both IGF-1 and IGFBP3 were found reduced from the referral until 2 years post-HSCT compared with healthy sex- and age-matched individuals, but, for individuals homozygous of the known high-producer minor allele of rs1520220 (IGF1), rs978458 (IGF1), or rs2854744 (IGFBP3) serum levels remained normal during the whole period. In accordance, maximum C-reactive protein levels were lower for these genotypes ofIGF1(rs1520220: median 66 vs. 102 mg/L,P= 0.005 and rs978458: 53 vs. 104 mg/L,P< 0.001), translating into borderline significant superior survival (P= 0.060 for rs1520220) and reduced treatment-related mortality (P= 0.050 for rs978458). In conclusion, we found that three SNPs in the IGF-1 axis with known functional impact were associated with circulating IGF-1 or IGFBP-3 levels also in the setting of HSCT, and predictive of the severity of the toxic-inflammatory response during the treatment.
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