BACKGROUND: Leukocyte trafficking, regulated by chemokine ligands and their receptors, involves in the pathogenesis of graft-versus-host disease (GVHD) including CC ligand 5 (CCL5) or CC receptor 5 (CCR5). The current study analyzed the association of acute or chronic GVHD (cGVHD) with the CCR5/CCL5 gene single nucleotide polymorphisms (SNPs) of recipients and donors. METHODS: We evaluated the SNPs of CCL5 promoter gene at position -28 (rs1800825)/-403 (rs2107538) and CCR5 gene at 59029 (rs1799987) in 72 recipients and donors using polymerase chain reaction/RFLP (Restriction Fragment Length Polymorphism) methods. RESULTS: With a median follow up of 924 days for survivors (range 48-2,360 days), the CG genotype of CCL5 gene at position -28 in recipients was significantly associated with a higher incidence of cGVHD (P=0.004), extensive cGVHD (P=0.038 by Seattle's criteria), and severe grade of cGVHD at presentation (P=0.017 by prognostic grading by Apkek et al.) compared to CC genotype. In terms of haplotype analysis, the recipients with AG haplotype of CCL5 gene also showed a higher incidence of cGVHD (P=0.003), extensive cGVHD (P=0.023), and more severe grade of cGVHD (P=0.020). However, there was no association of CCL5/CCR5 SNPs with acute GVHD. The donors' genotype of CCL5/CCR5 was not associated with the risk of cGVHD. CONCLUSION: The CCL5 promoter gene polymorphism of recipients was associated with the risk of cGVHD and its severity. The current study suggested an involvement of CCL5 in leukocyte trafficking for the development of cGVHD.
BACKGROUND: Leukocyte trafficking, regulated by chemokine ligands and their receptors, involves in the pathogenesis of graft-versus-host disease (GVHD) including CC ligand 5 (CCL5) or CC receptor 5 (CCR5). The current study analyzed the association of acute or chronic GVHD (cGVHD) with the CCR5/CCL5 gene single nucleotide polymorphisms (SNPs) of recipients and donors. METHODS: We evaluated the SNPs of CCL5 promoter gene at position -28 (rs1800825)/-403 (rs2107538) and CCR5 gene at 59029 (rs1799987) in 72 recipients and donors using polymerase chain reaction/RFLP (Restriction Fragment Length Polymorphism) methods. RESULTS: With a median follow up of 924 days for survivors (range 48-2,360 days), the CG genotype of CCL5 gene at position -28 in recipients was significantly associated with a higher incidence of cGVHD (P=0.004), extensive cGVHD (P=0.038 by Seattle's criteria), and severe grade of cGVHD at presentation (P=0.017 by prognostic grading by Apkek et al.) compared to CC genotype. In terms of haplotype analysis, the recipients with AG haplotype of CCL5 gene also showed a higher incidence of cGVHD (P=0.003), extensive cGVHD (P=0.023), and more severe grade of cGVHD (P=0.020). However, there was no association of CCL5/CCR5 SNPs with acute GVHD. The donors' genotype of CCL5/CCR5 was not associated with the risk of cGVHD. CONCLUSION: The CCL5 promoter gene polymorphism of recipients was associated with the risk of cGVHD and its severity. The current study suggested an involvement of CCL5 in leukocyte trafficking for the development of cGVHD.
Authors: Carolina Martínez-Laperche; Elena Buces; M Carmen Aguilera-Morillo; Antoni Picornell; Milagros González-Rivera; Rosa Lillo; Nazly Santos; Beatriz Martín-Antonio; Vicent Guillem; José B Nieto; Marcos González; Rafael de la Cámara; Salut Brunet; Antonio Jiménez-Velasco; Ildefonso Espigado; Carlos Vallejo; Antonia Sampol; José María Bellón; David Serrano; Mi Kwon; Jorge Gayoso; Pascual Balsalobre; Álvaro Urbano-Izpizua; Carlos Solano; David Gallardo; José Luis Díez-Martín; Juan Romo; Ismael Buño Journal: Blood Adv Date: 2018-07-24
Authors: Paul J Martin; Wenhong Fan; Barry E Storer; David M Levine; Lue Ping Zhao; Edus H Warren; Mary E D Flowers; Stephanie J Lee; Paul A Carpenter; Michael Boeckh; Sangeeta Hingorani; Li Yan; Qiang Hu; Leah Preus; Song Liu; Stephen Spellman; Xiaochun Zhu; Marcelo Pasquini; Philip McCarthy; Daniel Stram; Xin Sheng; Loreall Pooler; Christopher A Haiman; Lara Sucheston-Campbell; Theresa Hahn; John A Hansen Journal: Blood Date: 2016-10-06 Impact factor: 22.113
Authors: David H McDermott; Susan E Conway; Tao Wang; Stacy M Ricklefs; Manza A Agovi; Stephen F Porcella; Huong Thi Bich Tran; Edgar Milford; Stephen Spellman; Reza Abdi Journal: Blood Date: 2010-01-12 Impact factor: 22.113