To establish optimal reference values for recovered immune cell subsets, we prospectively investigated post-transplant immune reconstitution (IR) in 144 patients who received allogeneic stem cell transplantation (allo- SCT) and without showing any of the following events: poor graft function, grades II‒IV acute graft-versus-host disease (GVHD), serious chronic GVHD, serious bacterial infection, invasive fungal infection, or relapse or death in the first year after transplantation. IR was rapid in monocytes, intermediate in lymphocytes, CD3 Tcells, CD8 T cells, and CD19 B cells, and very slow in CD4 T cells in the entire patient cohort. Immune recovery was generally faster under HLA-matched sibling donor transplantation than under haploidentical transplantation. Results suggest that patients with an IR comparable to the reference values display superior survival, and the levels of recovery in immune cells need not reach those in healthy donor in the first year after transplantation.We suggest that data from this recipient cohort should be used as reference values for post-transplant immune cell counts in patients receiving HSCT.
Adolescent ; Adult ; Child ; Child, Preschool ; China ; Disease-Free Survival ; Female ; Graft vs Host Disease ; immunology ; mortality ; HLA Antigens ; immunology ; Hematopoietic Stem Cell Transplantation ; Humans ; Immune Reconstitution ; Male ; Middle Aged ; Reference Values ; Siblings ; T-Lymphocytes ; immunology ; Tissue Donors ; Transplantation, Homologous ; Young Adult

BACKGROUND: The interaction between killer immunoglobulin-like receptors (KIRs) and HLA class I regulates natural killer (NK) cell cytotoxicity and function. The impact of NK cell alloreactivity through KIR in liver transplantation remains unelucidated. Since the frequency of HLA-C and KIR genotypes show ethnic differences, we assessed the impact of HLA-C, KIR genotype, or KIR-ligand mismatch on the allograft outcome of Korean liver allografts. METHODS: One hundred eighty-two living donor liver transplant patients were studied. Thirty-five patients (19.2%) had biopsy-confirmed acute rejection (AR), and eighteen (9.9%) had graft failure. The HLA-C compatibility, KIR genotypes, ligand-ligand, and KIR-ligand matching was retrospectively investigated for association with allograft outcomes. RESULTS: Homozygous C1 ligands were predominant in both patients and donors, and frequency of the HLA-C2 allele in Koreans was lower than that in other ethnic groups. Despite the significantly lower frequency of the HLA-C2 genotype in Koreans, donors with at least one HLA-C2 allele showed higher rates of AR than donors with no HLA-C2 alleles (29.2% vs 15.7%, P=0.0423). Although KIR genotypes also showed ethnic differences, KIR genotypes and the number of activating KIR/inhibitory KIR were not associated with the allograft outcome. KIR-ligand mismatch was expected in 31.6% of Korean liver transplants and had no impact on AR or graft survival. CONCLUSIONS: This study could not confirm the clinical impact of KIR genotypes and KIR-ligand mismatch. However, we demonstrated that the presence of HLA-C2 allele in the donor influenced AR of Korean liver allografts.
Adult ; Alleles ; Asian Continental Ancestry Group/*genetics ; Female ; Genotype ; Graft Rejection ; Graft Survival ; HLA-C Antigens/*genetics ; Homozygote ; Humans ; Killer Cells, Natural/cytology/immunology ; Ligands ; *Liver Transplantation ; Male ; Middle Aged ; Proportional Hazards Models ; Receptors, KIR/chemistry/*genetics/metabolism ; Republic of Korea ; Tissue Donors ; Transplantation, Homologous

To explore the role of dentritic epidermal T lymphocytes ( DETCs) in immune rejection of skin allograft in mice and its related mechanism. Methods (1) Full-thickness skin was harvested from back of one male wild type (WT) C57BL/6 mouse. Epithelial cells were isolated for detection of the expression of DETCs and their phenotype with flow cytometer. Another male WT C57BL/6 mouse was used to harvest full-thickness skin from the back. Epidermis was isolated for observation of the morphological characteristics of DETCs with immunofluorescence technology. (2) Four male green fluorescence protein (GFP)-marked C57BL/6 mice, 7 female WT C57BL/6 mice (group WT), and 7 female ybT lymphocytes 8 gene knock-out (GK) C57BL/6 mice (group GK) were used. Full-thickness skin in the size of 1.4 cm x 1.4 cm on the back of mice in groups WT and GK were excised, and the wounds were transplanted with full-thickness skin in the size of 1.2 cm x 1.2 cm obtained from male GFP-marked C57BL/6 mice. The survival time of skin grafts was affirmed with small animal in vivo imager and naked eyes and recorded. (3) Two male WT C57BL/6 mice were used to isolate epithelial cells. Cells were inoculated into 48-well plate and divided into activation group (A) and control group (C) according to the random number table, with 4 wells in each group. Cells in group A were treated with 10 pL concanavalin A in the concentration of 2 microg/mL for 24 hours, while those in group C with PBS in the same volume as that in group A. The expression of interferon y in DETCs was detected with flow cytometer. (4) Four male GFP-marked C57BL/6 mice were used as donors. Fourteen female WT C57BL/6 mice were used as receptors and divided into interferon gamma neutralizing group (IN) and control group (C) according to the random number table, with 7 mice in each group. The skin transplantation model of C57BL/6 male to C57BL/6 female was established as in part (2). Before surgery and 72 hours after, mice in group IN were intraperitoneally injected with 200 pL interferon y neutralizing antibody in the concentration of 1 mg/mL, and those in group C with normal saline in the same volume as that in group IN. The survival time of skin grafts was observed and recorded using the methods in part (2), and the result of group IN was compared with that of group GK in part (2). The survival curve of skin grafts was processed with Log-rank ( Mantel-Cox) test. Results (1) The positive expression rate of DETCs in epithelial cells of skin in mouse was 7.27%, and they were all CD3 cells. DETCs were found to be scattered in the epidermis of skin in mouse with dendritic morphology. (2) The survival time of skin grafts of mice in group GK was 22-35 d, obviously longer than that in group WT (12-16 d, y2 = 14. 10 , P < 0.001). (3) Expression of interferon gamma was detected in 22. 70% DETCs in group A, which was obviously higher than that in group C (0.51%). (4) The survival time of skin grafts of mice in group IN was 19-24 d, which was obviously longer than that in group C (12-16 d, chi 2 = 13.60, P < 0.001) but close to that in group GK as in part (2) (chi2 = 0.06, P = 0.810). Conclusions DETCs are involved in promotion of immune rejection of skin allograft probably by secretinf interferon gamma.
Allografts ; Animals ; Epidermis ; Female ; Graft Survival ; immunology ; physiology ; Interferon-gamma ; immunology ; metabolism ; Lymphocytes ; Male ; Mice ; Mice, Inbred C57BL ; Skin ; Skin Transplantation ; T-Lymphocytes ; immunology

BACKGROUND/AIMS: BK virus-associated nephropathy (BKVAN) is an important cause of allograft dysfunction in kidney transplant recipients. It has an unfavorable clinical course, and no definite treatment guidelines have yet been established. Here, we report our center's experience with biopsy-proven BKVAN and investigate factors associated with its progression. METHODS: From January 2004 to April 2013, 25 patients with BKVAN were diagnosed by biopsy at Seoul St. Mary's Hospital. Of the 25 patients, 10 were deceaseddonor transplant recipients and 15 were living-donor transplant recipients. Three of the patients underwent retransplantation. The primary immunosuppressant used was tacrolimus in 17 patients and cyclosporine in eight patients. RESULTS: BKVAN was observed at a mean duration of 22.8 ± 29.1 months after transplantation. The mean serum creatinine level at biopsy was 2.2 ± 0.7 mg/dL. BKVAN occurred with acute rejection in eight patients (28%). Immunosuppression modification was performed in 21 patients (84%). Additionally, leflunomide and intravenous immunoglobulin were administered to 13 patients (52%) and two (8%), respectively. Allograft loss occurred in five patients (27.8%) during the follow- up period at 0.7, 17.1, 21.8, 39.8, and 41.5 months after the BKVAN diagnosis. Advanced stages of BKVAN, increased creatinine levels, and accompanying acute rejection at the time of BKVAN diagnosis increased the risk of allograft failure. CONCLUSIONS: The clinical outcomes in patients with biopsy-proven BKVAN were unfavorable in the present study, especially in patients with advanced-stage BKVAN, poor renal function, and acute allograft rejection.
Adult ; Allografts ; Antiviral Agents/therapeutic use ; BK Virus/*pathogenicity ; Biomarkers/blood ; Biopsy ; Creatinine/blood ; Disease Progression ; Female ; Graft Rejection/diagnosis/drug therapy/immunology/*virology ; Graft Survival ; Humans ; Immunocompromised Host ; Immunosuppressive Agents/adverse effects ; Kaplan-Meier Estimate ; Kidney Transplantation/*adverse effects ; Male ; Middle Aged ; Opportunistic Infections/diagnosis/drug therapy/immunology/*virology ; Polyomavirus Infections/diagnosis/drug therapy/immunology/*virology ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Time Factors ; Treatment Outcome ; Tumor Virus Infections/diagnosis/drug therapy/immunology/*virology

No abstract available.
Adult ; Female ; Graft Rejection/immunology/*prevention & control ; Graft Survival ; *Hematopoietic Stem Cell Transplantation ; Humans ; *Immune Tolerance ; Immunosuppressive Agents/therapeutic use ; Kidney Failure, Chronic/diagnosis/*surgery ; *Kidney Transplantation ; Living Donors ; Siblings ; Time Factors ; *Transplantation Chimera ; Treatment Outcome

BACKGROUND/AIMS: Patients who undergo repeat kidney transplantations (KTs) are considered at high risk for experiencing immunologic and non-immunologic complications. In this study, we investigated the clinical outcomes, including medical and surgical complications, of patients who underwent a third KT at our center. METHODS: Between March 1969 and December 2012, a total of 2,110 KTs were performed at the Seoul St. Mary's Hospital. Of them, we examined 11 patients who underwent a third KT, and investigated the allograft outcomes and complication rates. RESULTS: The mean follow-up duration after KT was 72.4 ± 78.3 months. The mean age at KT was 38.2 ± 8.0 years, and seven patients (63.6%) were males. Nine patients (81.8%) underwent living-donor KT. A cross-match test yielded positive results in four of the nine patients, and all underwent pretransplant desensitization therapy. After KT, three patients (27.2%) showed delayed graft function. Acute rejection developed in four patients (36.4%), and surgical complications that required surgical correction occurred in three patients. Allograft failure developed due to acute rejection (n = 3) or chronic rejection (n = 1) in four patients. Allograft survival rates at 1, 5, and 10 years were 81.8%, 42.9%, and 42.9%, respectively; however, the allograft survival rate at 5 years was > 80% in patients who underwent KT only after results of the panel reactive antibody test became available. CONCLUSIONS: Thus, a third KT procedure may be acceptable, although aggressive pretransplant immune monitoring and patient selection may be required to reduce the risks of acute rejection and surgical complications.
Acute Disease ; Adult ; Allografts ; Chronic Disease ; Delayed Graft Function/diagnosis/*etiology/therapy ; Female ; Graft Rejection/diagnosis/*immunology/therapy ; Graft Survival ; *Histocompatibility ; Humans ; Immunosuppressive Agents/therapeutic use ; Kidney Transplantation/*adverse effects ; Male ; Middle Aged ; Patient Selection ; Reoperation ; Republic of Korea ; Risk Assessment ; Risk Factors ; Time Factors ; Treatment Outcome

OBJECTIVETo investigate the pathological and immunological changes of renal grafts in recipients experiencing graft rejection.

METHODSThe clinicopathologic data of 56 renal needle biopsy samples obtained from renal transplant recipients were analyzed retrospectively. The specimens were classified histopathologically according to the Banff 2009 classification system and analyzed by immunohistochemical labeling and immunofluorescence.

RESULTSIn the 56 recipients, 1 (1.79%) experienced hyperacute rejection, 8 (14.29%) had suspected acute rejection, 12 (21.43%) developed acute T-cell rejection, 6 (10.71%) had acute antibody-mediated rejection, 2 (3.57%) had acute T-cell rejection with acute antibody-mediated rejection, 12 (21.43%) had chronic active T cell-mediated rejection, 2 (3.57%) had chronic active antibody-mediated rejection, 2 (3.57%) had chronic active T cell-mediated rejection with antibody-mediated rejection, 8 (14.29%) had non-specific interstitial fibrosis and tubular atrophy, and 3 (5.36%) had normal graft function. The expression levels of immune markers CD3, CD4, CD8, CD20, GrB and perforin differed with the types of T cell-mediated graft rejection, and the positivity and expression levels of these markers tended to increased with the severity of graft rejection. The expression of C4d was positive in all cases with antibody-mediated graft rejection.

CONCLUSIONSThe pathological characteristics of the renal biopsy specimens and expression levels of the immune markers allow timely and accurate evaluation of graft rejection type to provide a reliable pathological and etiological basis for clinical treatment and prognostic assessment.

Adolescent ; Adult ; Aged ; Female ; Graft Rejection ; immunology ; pathology ; Graft Survival ; Humans ; Kidney ; immunology ; pathology ; Kidney Transplantation ; adverse effects ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

Several studies have suggested that a positive lymphocyte cross-matching (XM) is associated with low graft survival rates and a high prevalence of acute rejection after adult living donor liver transplantations (ALDLTs) using a small-for-size graft. However, there is still no consensus on preoperative desensitization. We adopted the desensitization protocol from ABO-incompatible LDLT. We performed desensitization for the selected patients according to the degree of T lymphocyte cross-match titer, model for end-stage liver disease (MELD) score, and graft liver volume. We retrospectively evaluated 230 consecutive ALDLT recipients for 5 yr. Eleven recipients (4.8%) showed a positive XM. Among them, five patients with the high titer (> 1:16) by antihuman globulin-augmented method (T-AHG) and one with a low titer but a high MELD score of 36 were selected for desensitization: rituximab injection and plasmapheresis before the transplantation. There were no major side effects of desensitization. Four of the patients showed successful depletion of the T-AHG titer. There was no mortality and hyperacute rejection in lymphocyte XM-positive patients, showing no significant difference in survival outcome between two groups (P=1.000). In conclusion, this desensitization protocol for the selected recipients considering the degree of T lymphocyte cross-match titer, MELD score, and graft liver volume is feasible and safe.
ABO Blood-Group System/immunology ; Adult ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Desensitization, Immunologic/*methods ; End Stage Liver Disease/surgery ; Female ; Graft Rejection/immunology ; Graft Survival/*immunology ; Histocompatibility Testing ; Humans ; Liver/surgery ; *Liver Transplantation ; Living Donors ; Male ; Middle Aged ; Plasmapheresis ; Preoperative Care ; Retrospective Studies ; Severity of Illness Index ; Survival Rate ; T-Lymphocytes/*immunology ; *Transplant Recipients

OBJECTIVETo establish a calculated panel reactive antibody (CPRA) method to analyze the donor-recipient incompatibility rate in PRA-positive kidney recipients and estimate the probability of these recipients to receive kidney transplantation.

METHODSBased on the database of HLA-A, -B, -DR genes and A-B, A-DR, B-DR, A-B-DR haplotype frequencies collected from 2004 donors from Jan 2000 to Dec 2012, we analyzed CPRA in 202 PRA-positive recipients and evaluated the consistency between PRA and CPRA assessments using a CPRA-Java calculator software, which returned a percentage of CPRA (representing the probability of unacceptable HLA in the donor group) after input of HLA-specific antibodies of a PRA-positive recipient.

RESULTSThe mean PRA intensity of the 202 PRA-positive recipients was (23.12∓17.83)% with a mean CPRA% of (46.07∓23.30)%. A significant difference was found between the mean PRA% and CPRA% in low sensitized recipients (PRA 0-10%) [(6.87∓2.41)% vs (21.63∓11.75)%, P<0.05) and in moderately sensitized recipients (PRA 10%-30%) [(20.15∓5.70)% vs (50.56∓16.86)%, P<0.05), but not in highly sensitized recipients (PRA>30%); The concordance rates between PRA% and CPRA% in the 3 groups were 19.35% (P<0.05), 10.99% (P<0.05), and 100% (P>0.05), respectively.

CONCLUSIONSLowly sensitized kidney recipients might have a lower probability of actually receiving a transplant than PRA% shows. A PRA%>30% is a risk factor for kidney transplantation. PRA reflects the sensitized level of a renal recipient, and reliable detection of HLA antibody specificity is of critical importance. CPRA accurately reflects the probability of a recipient to receive a transplant to assist clinicians in predicting the waiting time and selecting the transplant approach.

Antibodies ; Antibody Specificity ; Graft Rejection ; immunology ; Graft Survival ; immunology ; HLA Antigens ; genetics ; Haploidy ; Histocompatibility Testing ; methods ; Humans ; Kidney Transplantation

OBJECTIVETo analyze the correlation between survival time after liver transplantation and the intracellular (i)ATP levels of CD4+ T cells.

METHODSLiver transplantation patients treated in our hospital,and with complete follow-up data,were enrolled retrospectively in our study (between July 2010 to October 2012) and divided into six groups according to survival time: less than 1 year,1-2 years,2-3 years,3-4 years,4-8 years,and more than 8 years.The less than 1 year survival group was further sub-divided for survival less than 1 month,1-2 months,2-3 months,3-5 months and 5-12 months.Blood samples collected from all enrollees (n=273) were analyzed by the Cylex ImmuKnow Cell Function Assay to detect the iATP level in CD4+ T cells.Correlation of iATP level in CD4+ T cells with survival time was statistically analyzed.

RESULTSThe levels of CD4+ T cell-iATP were significantly different among the various survival recipient groups by years: less than 1 year:325+228 ng/ml,1-2 years:216-147 ng/ml,2-3 years:225-172 ng/ml,3-5 years:236-184 ng/ml,4-8 years:298-145 ng/ml,more than 8 years:323-153 ng/ml.In addition,the levels of CD4+ T cell-iATP were significantly different between the groups of patients who survived less than 1 year: less than 1 month:441+255 ng/ml,1-2 months:357-235 ng/ml,2-3 months:353-257 ng/ml,3-5 months:202-123 ng/ml,5-12 months:234-145 ng/ml.

CONCLUSIONThere is a relationship between levels of iATP in CD4+ T cells and survival time after liver transplantation.For patients with postoperative survival time of less than 1 year,the CD4+ T cell iATP level will not accurately reflect the status of CD4+ T cells' immune activation.For patients with postoperative survival time of 2-4 years,the CD4+ T cell-iATP level is relatively low and the CD4+ T lymphocyte activation status is in the low reaction zone.Patients with postoperative survival time of more than 5 years had higher CD4+ T cell-iATP level then 2-4 years survivors,and had stable CD4+ T cell immune activation.

Adenosine Triphosphate ; immunology ; CD4-Positive T-Lymphocytes ; immunology ; Graft Survival ; Humans ; Immunosuppressive Agents ; Liver Transplantation ; Lymphocyte Activation ; Retrospective Studies ; Transplant Recipients