OBJECTIVE: To investigate the correlation between serum interleukin-33 (IL-33), β₂microglobulin (β₂-MG) levels and Durie-Salmon (DS) stage in patients with multiple myeloma (MM). METHODS: 100 MM patients admitted to the First Affiliated Hospital of Fujian Medical University from March 2019 to January 2021 were selected and divided into stage I, stage II and stage III groups according to the DS staging system. A baseline data questionnaire of patients was designed, then the relevant baseline data and laboratory test results of patients were recorded. The levels of serum IL-33 and β₂-MG of all patients were detected, and the correlation between serum IL-33, β₂-MG levels and DS stage of MM patients was analyzed. RESULTS: Among the 100 patients with MM, there were 32 cases in stage I, 39 cases in stage II and 29 cases in stage III. The levels of serum CRP and β₂-MG of patients in stage III were significantly higher than those of patients in stage I and II, and the levels of serum CRP and β₂-MG of patients in stage II were significantly higher than those of patients in stage I, the differences were statistically significant (P <0.05). The level of serum IL-33 of patients in stage III was significantly lower than that of patients in stage I and II, and the level of serum IL-33 of patients in stage II was significantly lower than that of patients in stage I, the differences were statistically significant (P <0.05). There was no statistical significant difference in other data between groups (P >0.05). Kendall's tau-b correlation analysis showed that the levels of serum CRP and β₂-MG were positively correlated with DS stage in MM patients (r =0.534, 0.776), the level of serum IL-33 was negatively correlated with DS stage in MM patients (r =-0.759). Ordered logistic regression analysis and forest plot showed that the low level of serum IL-33 and the high level of β₂-MG were the influencing factors of high DS stage in MM patients (P <0.05 ). CONCLUSION DS stage of MM patients is closely related to the levels of serum IL-33 and β₂-MG, that is, the lower the serum IL-33 level and the higher the β₂-MG level, and the higher the DS stage of MM patients.
Humans ; Interleukin-33 ; Multiple Myeloma ; Prognosis ; HLA-G Antigens/blood*

OBJECTIVE: To observe the expression of helper T cells 17(Th17), interleukin 23 (IL-23) in peripheral blood in patients with acute myeloid leukemia (AML), to analyze the relationship between Th17, IL-23 in peripheral blood and immunophenotype. METHODS: 105 patients with AML in the hospital from January 2019 to January 2021 were prospectively selected as the research subjects, the expression of Th17 and IL-23 in peripheral blood of patients with AML was detected by flow cytometry; immunophenotype was detected and counted. The relationship between the expression of Th17, IL-23 in peripheral blood and immunophenotype of AML patients was analyzed. Draw ROC curve and analyze the predictive value of Th17 and IL-23 expression in peripheral blood to immunophenotype. RESULTS: The immunophenotype results of AML patients showed that myeloid antigen, lymphoid antigen and hematopoietic stem/progenitor cell marker antigen were positive expressed for various antigens in 105 AML patients, in myeloid antigens, CD13⁺ accounted for the highest proportion (93.33%), in lymphoid antigens, CD56⁺ accounted for the highest proportion (32.38%), and in hematopoietic stem/progenitor cell marker antigens, CD38⁺ accounted for the highest proportion (68.57%). The expression of Th17 in peripheral blood of AML patients with CD56⁺, CD7⁺, CD34⁺ and human leukocyte antigen DR⁺(HLA-DR⁺) were higher than that of AML patients with CD56^-, CD7^-, CD34^-, HLA-DR^-, the expression of IL-23 in peripheral blood of AML patients with CD56⁺, CD34⁺ and HLA-DR⁺ were higher than that of AML patients with CD56^-, CD34^-, HLA-DR^-, the differences were statistically significant (P<0.05); compared the expression of Th17 and IL-23 in peripheral blood between other antibody positive and negative patients, there was no statistical significant difference (P>0.05). Logistic regression analysis showed that the high expression of Th17 in patients with AML was related to the positive expression of CD56, CD7, CD34 and HLA-DR in the detection of immunophenotype, the high expression of IL-23 was related to the positive expression of CD56, CD34 and HLA-DR in the detection of immunophenotype. The ROC curve showed that the AUC of expression levels of Th17 and IL-23 in peripheral blood alone and in combination for predicting CD56⁺, CD34⁺, HLA-DR⁺ and Th17 in peripheral blood for predicting CD7⁺ were mostly 0.5-0.7, which had certain predictive value, but the predictive performance was low. CONCLUSION Myeloid antigen, lymphoid antigen and hematopoietic hematopoietic stem/progenitor cell marker antigen are positive expressed for various antigens in AML patients, the high expression of Th17 in peripheral blood of AML patients is related to the positive expression of CD56, CD7, CD34 and HLA-DR in detection of immunophenotyping, the high expression of IL-23 is related to the positive expression of CD56, CD34 and HLA-DR in the detection of immunophenotype.
Antigens, CD34 ; Flow Cytometry/methods* ; HLA-DR Antigens/analysis* ; Humans ; Immunophenotyping ; Interleukin-23 ; Interleukin-23 Subunit p19/blood* ; Leukemia, Myeloid, Acute/genetics* ; Th17 Cells

Allogeneic stem cell transplantation (allo-SCT) is currently the only curative option for patients with X-linked agammaglobulinemia (XLA). In this study, patient 1 aged 4 years who underwent allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from HLA-mismatched unrelated donor; patient 2 aged 24 years (childhood onset) with primary cutaneous acral CD8 T cell lymphoma who underwent allo-PBSCT from haploidentical relative donor. Both were treated by reduced toxicity myeloablative conditioning with post-transplantation cyclophosphamide (PTCy), anti-thymocyte globulin (ATG), methotrexate (MTX) and cyclosporine (CsA) for graft-versus-host-disease (GVHD) prophylaxis. In patient 1, neutrophil and platelet engraftment were observed on day 11 post-transplantation; the donor chimerism dropped on day 90 post-transplantation, and recovered on day 150 with donor lymphocyte infusion (DLI). In patient 2, neutrophil and platelet engraftment were observed on days 20 and 87 post-transplantation respectively, with complete donor chimerism on day 30 post-transplantation. The serum levels of IgG, IgM and IgA and the percentage of CD19 B cells in peripheral blood of patients 1 and 2 returned to normal within 2 months and more than 1 year after transplantation respectively. There was no evidence of acute GVHD for the two patients. Patient 1 developed a limited type of skin chronic GVHD after DLI, which disappeared after anti-GVHD treatment. This is the first report of successful treatment for two XLA patients using PTCy with allo-PBSCT from HLA-mismatched unrelated donor or haploidentical donor, combining with improved conditioning, which expands the pool of eligible donors for patients with XLA.
Agammaglobulinemia ; therapy ; Genetic Diseases, X-Linked ; therapy ; Graft vs Host Disease ; HLA Antigens ; Hematopoietic Stem Cell Transplantation ; Humans ; Peripheral Blood Stem Cell Transplantation ; Treatment Outcome ; Unrelated Donors ; Young Adult

Objective: To explore the impact of the natural killer cell immunoglobulin-like receptor/human leukocyte antigen (KIR/HLA) receptor-ligand model in single unrelated cord blood transplantation (sUCBT) . Methods: Between July 2012 and June 2018, 270 patients with malignant hematologic diseases receiving single-unit UCBT were divided into two groups. Group 1 (n=174) patients lacked a C-ligand for inhibitory KIR on UCB NK cells (patients homozygous C1/C1 or C2/C2) . Group 2 (n=96) patients expressed both C ligands for inhibitory KIR in the receptor (patients heterozygous C1/C2) . Results: A total of 270 patients (146 males, 124 females) with a median age of 13 years (1-62) were included in this retrospective study. All patients received a myeloablative conditioning regimen (without ATG) . The ratio of neutrophil engraftment for group 1 and 2 were both 98.9%, the median time of neutrophil engraftment for group 1 and 2 was 16 (10-41) days vs 17 (11-33) days (P=0.705) . The ratio of platelet engraftment was 88.5% for group 1 and 87.5% for group 2, the median time of platelet engraftment was 35 (11-113) days vs 38.5 (13-96) days (P=0.317) . The cumulative incidence of Ⅱ-Ⅳ acute GVHD in 100 days was 38.7% (95%CI 31.4%-45.9%) for group 1 and 50.0% (95%CI 39.6%-59.6%) for group 2 (P=0.075) , but multivariate analysis showed that HLA-C ligand absence was an independent protective factor for Ⅱ-Ⅳ acute GVHD after transplantation (P=0.036) . Patients in absence of a C-ligand for inhibitory KIRs (Group 1) showed a lower relapse rate than patients with both C-ligands (group 2) : 17.7% (95%CI 11.7%-24.9%) vs 22.7% (95%CI 4.4%-32.2%) after 3 years (P=0.288) . The median follow-up time was 742 (335-2 512) days. The 3-year OS was 72.1% for group 1 and 60.5% for group 2 (P=0.079) . There was no statistically significant difference between the two groups in 3-year disease-free survival [64.9% (95%CI 56.2%-72.3%) vs 55.4% (95%CI 44.4%-65.0%) (χ(2)=3.027, P=0.082) ]. Non-relapse mortality for group 1 was 12.1% (95%CI 7.7%-17.4%) and for group 2 was 16.7% (95%CI 10.0%-24.8%) (P=0.328) . Conclusion: Patients lacking a KIR-ligand of HLA group C1 or C2 had a lower incidence of grades Ⅱ-Ⅳ acute GVHD after sUCBT.
Adolescent ; Adult ; Child ; Child, Preschool ; Cord Blood Stem Cell Transplantation ; Female ; Graft vs Host Disease ; HLA Antigens ; Hematologic Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation ; Humans ; Infant ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Receptors, KIR ; Retrospective Studies ; Young Adult

OBJECTIVETo study the relationship between the expression of peripheral blood HLA-DR, CD4CD25 regulatory T cells, IL-17 and IL-27 with liver damage in children with human cytomegalovirus (HCMV) infection.

METHODSTwenty-one HCMV children with liver damage and twenty-one HCMV children without liver damage were enrolled in this study. The expression of peripheral blood HLA-DR and CD4CD25 regulatory T cells was detected by flow cytometry. Plasma levels of IL-17 and IL-27 were measured using ELISA.

RESULTSThe plasma levels of IL-17 and IL-27 in children with liver damage were significantly higher than in those without liver damage, while the expression of peripheral blood CD4CD25 regulatory T cells was lower than in those without liver damage (P<0.05). Plasma IL-17 and IL-27 levels were negatively correlated with the expression of peripheral blood CD4CD25 regulatory T cells (P<0.01).

CONCLUSIONSImmune imbalance mediated by CD4CD25 regulatory T cells and over-expression of IL-17 and IL-27 may be involved in the pathogenesis of liver damage in children with HCMV infection.

CD4 Antigens ; immunology ; Cytomegalovirus ; physiology ; Cytomegalovirus Infections ; blood ; complications ; genetics ; Female ; Flow Cytometry ; HLA-DR Antigens ; genetics ; immunology ; Humans ; Infant ; Interleukin-17 ; blood ; genetics ; Interleukin-2 Receptor alpha Subunit ; immunology ; Interleukins ; blood ; genetics ; Liver ; injuries ; metabolism ; Liver Diseases ; blood ; etiology ; immunology ; Male ; T-Lymphocytes, Regulatory ; immunology

BACKGROUNDAcute graft-versus-host disease (aGVHD) is a common and severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Some studies have found that the presence of certain specific human leukocyte antigen (HLA) loci could affect the occurrence of aGVHD. Meanwhile, the impact of HLA haplotypes on aGVHD has been rarely studied. This study aimed to investigate the effects of HLA loci and haplotypes on intestinal aGVHD.

METHODSTotally, 345 consecutive patients undergoing first HLA-matched sibling peripheral blood stem cell transplantation (PBSCT) from February 2004 to June 2013 at Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, were enrolled in this study. HLA loci and haplotypes of recipients with frequency over 5% were searched and their effects on intestinal aGVHD were investigated. Other important factors including donor age, recipient age, donor-recipient sex combinations, and conditioning regimens were also evaluated using logistic regression. Pure upper gastrointestinal tract aGVHD without diarrhea was excluded because the histological proof was unavailable. The follow-up end-point was 6 months after HSCT.

RESULTSThe cumulative incidence of intestinal aGVHD was 19.4%, with 18.0% of the patients classified as classic aGVHD and 1.4% as persistent, recurrent, or late aGVHD. Multivariate analysis showed that HLA-A31 locus (odds ratio [OR] 2.893, 95% confidence interval [CI] [1.054, 7.935], P = 0.039), HLA B40-DR15 (OR 3.133, 95% CI [1.250, 7.857], P = 0.015), and HLA B46-DR9 haplotypes (OR 2.580, 95% CI [1.070, 6.220], P = 0.035), female donor for male recipient (OR 2.434, 95% CI [1.319, 4.493], P = 0.004) were risk factors for intestinal aGVHD.

CONCLUSIONThe presence of certain HLA loci and haplotypes may influence the occurrence of intestinal aGVHD in PBSCT with HLA-identical sibling donors.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Graft vs Host Disease ; genetics ; HLA Antigens ; genetics ; Haplotypes ; genetics ; Humans ; Intestines ; metabolism ; pathology ; Male ; Middle Aged ; Multivariate Analysis ; Peripheral Blood Stem Cell Transplantation ; methods ; Retrospective Studies ; Risk Factors ; Young Adult

Mesenchymal stem cells (MSCs) can be obtained from a variety of human tissues. Placenta has become an attractive stem cell source for potential applications in regenerative medicine and tissue engineering. The aim of this study was to localize and characterize MSCs within human chorionic membranes (hCMSCs). For this purpose, immunofluorescence labeling with CD105 and CD90 were used to determine the distribution of MSCs in chorionic membranes tissue. A medium supplemented with a synthetic serum and various concentrations of neurotrophic factors and cytokines was used to induce hCMSCs to neural cells. The results showed that the CD90 positive cells were scattered in the chorionic membranes tissue, and the CD105 positive cells were mostly located around the small blood vessels. hCMSCs expressed typical mesenchymal markers (CD73, CD90, CD105, CD44 and CD166) but not hematopoietic markers (CD45, CD34) and HLA-DR. hCMSCs differentiated into adipocytes, osteocytes, chondrocytes, and neuronal cells, as revealed by morphological changes, cell staining, immunofluorescence analyses, and RT-PCR showing the tissue-specific gene presence for differentiated cell lineages after the treatment with induce medium. Human chorionic membranes may be the source of MSCs for treatment of nervous system injury.
Adipocytes ; Blood Vessels ; Cell Lineage ; Chondrocytes ; Chorion* ; Cytokines ; Fluorescent Antibody Technique ; HLA-DR Antigens ; Humans* ; Membranes* ; Mesenchymal Stromal Cells* ; Nerve Growth Factors ; Neurons ; Osteocytes ; Placenta ; Regenerative Medicine ; Stem Cells ; Tissue Engineering ; Trauma, Nervous System

The expression of immunogenic markers after differentiation of umbilical cord blood (UCB)-derived mesenchymal stem cells (MSC) has been poorly investigated and requires extensive in vitro and in vivo testing for clinical application. The expression of human leukocyte antigen (HLA) classes on UCB-derived MSC was tested by Fluorescence-activated cell sorting analysis and immunocytochemical staining. The undifferentiated MSC were moderately positive for HLA-ABC, but almost completely negative for HLA-DR. The MSC differentiated to chondrocytes expressed neither HLA-ABC nor HLA-DR. The proliferation of MSC was not significantly affected by the allogeneic lymphocytes stimulated with concanavalin A. The responder lymphocytes showed no significant decrease in proliferation in the presence of the MSC, but the apoptosis rate of the lymphocytes was increased in the presence of MSC. Taken together, these findings indicate that UCB-derived MSC differentiated to chondrocytes expressed less HLA class I and no class II antigens. The MSC showed an immunomodulatory effect on the proliferation and apoptosis of allogeneic lymphocytes. These data suggest that the differentiated and undifferentiated allogeneic MSC derived from umbilical cord blood can be a useful candidate for allogeneic cell therapy and transplantation without a major risk of rejection.
Apoptosis ; Cell- and Tissue-Based Therapy ; Chondrocytes ; Concanavalin A ; Fetal Blood* ; Flow Cytometry ; Histocompatibility Antigens Class II ; HLA-DR Antigens ; Humans ; In Vitro Techniques ; Leukocytes ; Lymphocytes ; Mesenchymal Stromal Cells* ; Umbilical Cord*

OBJECTIVETo analyze the treatment outcome of a consecutive series of 100 leukemia patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSThe clinical data of leukemia patients received allo-HSCT were analyzed retrospectively, the therapeutic efficacy was summarized. 100 evaluable cases of leukemia included 47 cases of AML, 33 cases of ALL, 2 cases of AL (biphenotypic), 16 CML and 2 CMML. Before transplantation, 76 cases were in first complete remission, 9 cases in second or greater complete remission and 15 cases in non-remission or relapse. All the patients received peripheral blood hematopoietic stem cell transplantation (PBHSCT). The conditioning regimen of human leukocyte antigen (HLA)-matched allo-HSCT group was modified BuCy, but in HLA-mismatched group Fludarabine and anti-human thymocyte globulin (ATG) was added. CsA+MTX regimen was used for prophylaxis of graft-versus-host disease (GVHD) in HLA-identical allo-HSCT, while additional MMF was added in HLA-mismatched group. The average time of follow-up was 13 months.

RESULTSAt the last follow-up, 66.0% (66/100) patients survived, 53.0% (53/100) patients survived without leukemia, 28.0% (28/100) patients relapsed and 34.0% (34/100) patients died, 44.1% patients of them died from infectious pulmonary complications. During transplantation, 65.0% of the patients were suffered from lung infection. The overall survival (OS) and disease-free survival (DFS) of all cases was 60.9% and 48.8%, respectively. The recurrence rate was significantly higher in non-remission (66.7%) than in CR (21.2%) patients (P < 0.05). The cumulative incidence of GVHD in HLA-mismatched transplantation was 60.8%, which was significantly higher than that of HLA-matched transplantation (38.8%) (P < 0.05).

CONCLUSIONAllo-HSCT can cure a significant proportion of leukemia patients, especially for those in CR status. Since the incidence of infectious pulmonary complications after allo-HSCT is still high, much more attention should be paid to it. The comprehensive prognosis of HLA-matched transplantation is better than the HLA-mis-matched transplantation.

Antilymphocyte Serum ; therapeutic use ; Disease-Free Survival ; Graft vs Host Disease ; prevention & control ; HLA Antigens ; genetics ; Humans ; Incidence ; Leukemia ; therapy ; Peripheral Blood Stem Cell Transplantation ; Recurrence ; Retrospective Studies ; Transplantation Conditioning ; Treatment Outcome ; Vidarabine ; analogs & derivatives ; therapeutic use

Bone Marrow Transplantation ; history ; methods ; HLA Antigens ; immunology ; Hematopoietic Stem Cell Transplantation ; history ; methods ; History, 20th Century ; History, 21st Century ; Hospitals, General ; Humans ; Peripheral Blood Stem Cell Transplantation ; history ; methods ; Singapore ; Transplantation Conditioning ; history ; methods