scholarly journals An alpha‐defensin gene single nucleotide polymorphism modulates the gut microbiota and may alter the risk of acute graft‐ versus ‐host disease

2020 ◽  
Vol 189 (5) ◽  
pp. 926-930 ◽  
Author(s):  
Armin Rashidi ◽  
Adam Herman ◽  
Antonio L. C. Gomes ◽  
Jonathan U. Peled ◽  
Robert R. Jenq ◽  
...  
Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4073-4073
Author(s):  
Luis J. Espinoza ◽  
Akiyoshi Takami ◽  
Katsuya Nakata ◽  
Makoto Onizuka ◽  
Takakazu Kawase ◽  
...  

Abstract Abstract 4073 NOD-like receptor family, pyrin domain containing 3 (NLRP3) is an innate immune receptor that exerts functions in the regulation of inflammation and apoptosis. Recent studies have shown that the single nucleotide polymorphism (SNP) rs10754558 (C>G) at the 3' untranslated region of NLRP3 gene is functional and is associated with various immunological diseases. Allele G is linked with a higher activity of NLRP3 than allele A, and plays important roles in increased susceptibility to allergic reactions and in protection of HIV infection. This study retrospectively examined the impact of the NLRP3 genotype of a total 659 recipients with hematologic malignancies and their unrelated donors on the clinical outcomes in unrelated HLA 12/12 matched bone marrow transplantation (BMT) through the Japan Donor Marrow Program. The genotype frequencies of G/G, G/C and C/C were 19%, 50% and 31% in recipients and 18%, 49% and 32% in donors (P =0.79). The donor G/G or G/C genotype was associated with a significantly higher incidence of grades III to IV acute graft-versus-host disease (GVHD; 15% vs. 7%, P =0.004; Fig 1B) and a trend toward a higher incidence of grades II to IV acute GVHD (34% vs. 27%, P =0.06; Fig 1A), while no significant differences between the G/G genotype and G/C genotype were seen. The donor G/G or G/C genotype remained statistically significant in the multivariate analysis for the development of grades III to IV acute GVHD (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.22 to 3.90; P =0.009) as well as a trend toward an association with grades II-IV acute GVHD (HR, 1.31; 95% CI, 0.96 to 1.80; P =0.09). The recipient NLRP3 genotype did not significantly influence the transplant outcomes. These results suggest an association of the donor NLRP3 genotype with the development of acute GVHD after unrelated BMT. Genotyping for the NLRP3 rs10754558 could be useful in donor selection and risk-adapted management of transplanted patients, and may furthermore offer some novel therapeutic insights into the mechanisms of acute GVHD. Disclosures: No relevant conflicts of interest to declare.


2017 ◽  
Vol 122 ◽  
pp. 90-95 ◽  
Author(s):  
Kosuke Yoshioka ◽  
Kazuhiko Kakihana ◽  
Noriko Doki ◽  
Kazuteru Ohashi

2020 ◽  
Vol 4 (19) ◽  
pp. 4607-4617
Author(s):  
Kota Yoshifuji ◽  
Kyoko Inamoto ◽  
Yuko Kiridoshi ◽  
Kozue Takeshita ◽  
Satoshi Sasajima ◽  
...  

Abstract Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, management of aGVHD is important for successful transplantation. Mucosal damage and alteration of the gut microbiota after allo-HSCT are key factors in the development of aGVHD. We conducted a prospective study to evaluate the ability of prebiotics, which can alleviate mucosal damage and manipulate the gut microbiota, to mitigate posttransplantation complications, including aGVHD. Resistant starch (RS) and a commercially available prebiotics mixture, GFO, were administered to allo-HSCT recipients from pretransplantation conditioning to day 28 after allo-HSCT. Prebiotic intake mitigated mucosal injury and reduced the incidence of all aGVHD grades combined and of aGVHD grades 2 to 4. The cumulative incidence of skin aGVHD was markedly decreased by prebiotics intake. Furthermore, the gut microbial diversity was well maintained and butyrate-producing bacterial population were preserved by prebiotics intake. In addition, the posttransplantation fecal butyrate concentration was maintained or increased more frequently in the prebiotics group. These observations indicate that prebiotic intake may be an effective strategy for preventing aGVHD in allo-HSCT, thereby improving treatment outcomes and the clinical utility of stem cell transplantation approaches. This study was registered on the University Hospital Medical Information Network (UMIN) clinical trials registry (https://www.umin.ac.jp/ctr/index.htm) as #UMIN000027563.


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