Cytokine gene polymorphisms and graft-versus-host disease in children after matched sibling hematopoietic stem cell transplantation: a single-center experience

Abstract

Various polymorphisms in cytokine genes have recently been investigated as candidate risk factors in allogeneic hematopoetic stem cell transplantation (allo-HSCT). We retrospectively analyzed specific polymorphisms in genes for interleukin (IL)-10, IL-6, tumor-necrosis factor alpha (TNF-a) and interferon gamma (IFN-c) in a pediatric cohort of 57 histocompatibility leucocyte antigen (HLA)-identical sibling myeloablative transplants. Both recipient and donor genotypes were tested for association with graft-versus-host disease (GVHD) by statistical methods including Cox regression analysis. We found a significant association between the IL-10 promoter haplotype polymorphisms at positions -1082, -819 and -592 with the occurrence of severe (grades III-IV) acute GVHD (aGVHD). Recipients with the haplotype GCC had a statistically significant decreased risk of severe aGVHD (hazard risk (HR)50.20, 95% confidence interval (CI): 0.06-0.67) in comparison with patients with other IL-10 haplotypes (P50.008). Transplant-related mortality at 1 year was significantly lower in recipients with this haplotype (HR50.17, 95% CI: 0.012-0.320) versus other IL-10 haplotypes (P50.03), whereas overall survival was not influenced by IL-10 haplotype polymorphisms. In multivariate analysis, the presence of the IL-10 GCC haplotype was found as the only variable associated with a statistically significant decreased hazard of severe aGVHD development (P50.02, HR50.21, 95% CI: 0.05-0.78). These results suggest that pediatric patients possessing the IL-10 GCC haplotype may be protected from the occurrence of severe aGVHD in the setting of matched sibling HSCT.

Impact of HLA alleles and cytokine polymorphisms on inhibitors development in children with severe haemophilia A

“…Interestingly, the latter results do not corroborate with the literature findings [5,11,12]. Nonetheless, increased secretion of IL-10 (GCC haplotypes) promotes the differentiation, proliferation and antibody production of B lymphocytes [22][23][24]. Moreover, a body of evidence has accumulated indicating that IL-10 can have pleiotropic effects on adaptive and innate immunity cell mediators as well as a protective role from autoimmune diseases [25].…”

Advances in predicting acute GVHD

“…Three common haplotypes represent high (GCC), intermediate (ATA) and low (ACC) IL‐10 production (Suarez et al , ). As one might expect, the presence of the high‐producing (GCC) haplotype in HCT recipients correlated with decreased risk for aGVHD (Karabon et al , ; Goussetis et al , ). Contrary results were reported in one large study, however, that found the presence of recipient or absence of donor GCC haplotype increased risk for GVHD (Socie et al , ).…”

Relations of COVID-19-Related Stressors and Social Support With Chinese College Students' Psychological Response During the COVID-19 Pandemic

“…A large body of research literature has shown links between chronic and acute stress and short-or long-term psychological and physical disorders, such as anxiety, depression, and PTSD (5)(6)(7). Specifically, people who experience a large number of stressors related to infectious diseases tend to show more psychological symptoms (e.g., PTSD, depression) than those who experience fewer stressors (6,8). The COVID-19related stressors are those stressful events related with COVID-19 disease that might endanger their well-being, such as an important person being infected with COVID-19 or having to cancel a vacation due to the pandemic.…”