Objective To explore the impact of IL-10 gene polymorphisms on the outcome in HLA matched sibling hematopoietic stem cell transplantation (HSCT).Methods PCR-sequencespecific primer (PCR-SSP) assay was used to analyze the SNP of IL-10 in 77 recipient and donor pairs:-1082 A/G,-819 T/C,-592 C/A.Results IL-10 ATA/ATA (1082,-819,-592) genotype in recipients significantly decreased the incidence of grade Ⅱ-Ⅳ acute graft vursus-host disease (aGVHD) (6.1％ vs.25.0 ％,P＜0.05),reduced 5-year transplant-related mortality (TRM) (10.7 ％± 5.9％ vs.29.7％ ± 5.2％,P＜0.05) and increased disease free survival (DFS) (81.8％ ± 6.7％ vs.56.8％ ± 7.5％,P＜0.05).With regard to the donor genotype,the incidence of grade Ⅱ-Ⅳ aGVHD,extensive chronic GVHD,5-year TRM and DFS had no signicant difference between IL-10 ATA/ATA and non ATA/ATA subgroup.Multivariable analysis also revealed that IL-10 non-ATA/ATA genotype in recipients and high-risk status of disease were two independent risk factors for DFS (HR =2.911,P =0.029; HR =2.686,P =0.027).Conclusion In HLA-matched sibling HSCT,the presence of recipient IL-10 ATA/ATA significantly decreased the incidence of grade Ⅱ-Ⅳ aGVHD and TRM,and increased DFS.

OBJECTIVETo clarify the role of endothelial cells (ECs) injury induced by anti-endothelial cell antibody (AECA) in allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSSerum immunoglobulin (IgG) from allo-HSCT recipients were purified and incubated with human umbilical vein vascular endothelium (HUVEC) in vitro, then the functional changes and cell apoptosis were tested.

RESULTSAfter incubation with AECA positive IgG, soluble adhesion molecules significantly elevated in culture supernatant. When concentration of IgG was 160, 320, and 640 μg/ml, concentrations of soluble intercellular adhesion molecule-1 in supernatant were statistically higher in AECA positive groups [(117.10 ± 12.82) vs (78.17 ± 4.90) pg/ml, (151.30 ± 15.35) vs (89.46 ± 6.02) pg/ml, (239.00 ± 32.53) vs (127.80 ± 13.86) pg/ml, P<0.01)]. When concentration of IgG was 40, 80, 160, 320, and 640 μg/ml, concentrations of soluble vascular cell adhesion molecule-1 in supernatant were also statistically higher in AECA positive groups [(38.51 ± 3.76) vs (24.78 ± 2.59) pg/ml, (61.34 ± 6.99) vs (38.20 ± 3.17) pg/ml, (135.60 ± 24.46) vs (63.73 ± 5.08) pg/ml, (221.30 ± 29.40) vs (112.80 ± 8.91) pg/ml, (420.90 ± 31.70) vs (224.40 ± 20.79) pg/ml, P<0.01]. Clotting activity factors also elevated in culture supernatant after incubation with AECA positive IgG. When concentration of IgG was 80, 160, 320, and 640 μg/ml, concentrations of von Willebrand factor were statistically higher in AECA positive groups [(19.51 ± 0.72) vs (17.17 ± 0.60) ng/ml, P=0.0193; (22.97 ± 1.18) vs (18.27 ± 0.61) ng/ml, (26.40 ± 1.54) vs (19.53 ± 0.70) ng/ml, (34.35 ± 1.60) vs (23.81 ± 0.92) ng/ml, P<0.01]. When concentration of IgG was 320 and 640 μg/ml, concentrations of thrombomodulin were statistically higher in AECA positive groups [(57.50 ± 4.50) vs (40.31 ± 4.39) pg/ml, P=0.0132; (59.18 ± 4.11) vs (38.84 ± 5.16) pg/ml, P<0.01]. However, inflammatory factors (IL-1β, IL-6, IL-8 and ANG2) were not statistically different in AECA positive and negative groups (P>0.05). Moreover, IgG from AECA positive samples did not change the proliferation or cell apoptosis.

CONCLUSIONAECA from allo-HSCT recipients dysregulates ECs' function in vitro, but do not induce apoptosis, which is valuable in the pathophysiology of graft-versus-host disease (GVHD) and other complications after allo-HSCT.

Allografts ; Autoantibodies ; Endothelial Cells ; Endothelium, Vascular ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Intercellular Adhesion Molecule-1 ; Interleukin-6 ; Umbilical Veins ; von Willebrand Factor

OBJECTIVETo explore the impact of interleukin-18 (IL-18) single nucleotide polymorphisms on outcomes of hematologic malignancies with HLA-matched sibling donor hematopoietic stem cell transplantation (allo-HSCT).

METHODSSingle- nucleotide polymorphisms in IL-18 promoter was detected by PCR-sequence-specific primer analysis (PCR-SSP) in 93 recipients and their HLA matched sibling donors. Hematopoietic reconstitution, incidences of graft versus host disease (GVHD) and infections, transplant related mortality (TRM), and disease free survival (DFS) were analyzed.

RESULTSIn comparison with -137 G/C+C/C donor genotype, patients with -137 G/G donor genotype had shorter duration of neutrophil recovery [15(11-23) days vs 17(11-24) days, P=0.01], higher incidence of extensive chronic GVHD (20.6% vs 3.3%, P=0.029), but no difference in the interval of platelet recovery [20(11-46) days vs 20(7-38) days, P=0.844]. The incidence of extensive chronic GVHD in -607 C/C donor genotype (31.6%) was significantly higher than that (10.8%) in C/A + A/A donor genotype (P=0.024). Recipients with -607 C/C genotype also had higher incidence (33.3%) of extensive chronic GVHD than those with C/A+A/A genotype (10.7%, P=0.016). There were no differences in acute GVHD, TRM, and DFS between different genotypes.

CONCLUSIONIL-18 -137 G homozygous genotype in donor facilitated neutrophil reconstitution, but increased the risk of extensive chronic GVHD in patients with allo-HSCT.

Adolescent ; Adult ; Child ; Child, Preschool ; Disease-Free Survival ; Female ; Genotype ; Graft vs Host Disease ; epidemiology ; Hematologic Neoplasms ; genetics ; therapy ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Incidence ; Interleukin-18 ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Siblings ; Tissue Donors ; Transplantation, Homologous ; Young Adult