ABO-incompatible living-related kidney transplantation: report of 23 cases / 器官移植

Objective To evaluate clinical efficacy and safety of ABO-incompatible (ABOi) living-related kidney transplantation. Methods Clinical data of 23 recipients undergoing ABOi living-related kidney transplantation were retrospectively analyzed. According to the initial blood group antibody titers in the recipients before surgery, different individualized pretreatment regimens were adopted, including oral intake of immunosuppressive drugs plus rituximab, or oral intake of immunosuppressive drugs plus plasma exchange and/or double filtration plasmapheresis plus rituximab. The blood group antibody titers before and after pretreatment, before and after kidney transplantation, and perioperative renal function and related complications were monitored. Renal allograft function and related complications were observed during postoperative follow-up. Results Among 23 recipients undergoing ABOi living-related kidney transplantation, except for one case presenting with hyperacute rejection during operation, the serum creatinine levels of the remaining 22 recipients were restored normal. Perioperative complications included lymphatic fistula in 4 cases, 1 case of urinary fistula, 1 case of perirenal hematoma complicated with T cell-mediated rejection, 6 cases of urinary system infection, 1 case of acute tubular necrosis, 1 case of acute pancreatitis, 1 case of blood group antibody titer rebound, and 1 case of primary disease recurrence, and all of these complications were cured after corresponding treatment. During postoperative follow-up, the graft and recipient survival rates of 22 recipients were 100%, and renal allograft function was normal. The blood group antibody titer were all ≤1:8 during follow-up. Complications during follow-up included 2 cases of severe lung infection, 1 case of antibody-mediated rejection, 2 cases of primary disease recurrence, 1 case of lymphocyst, 1 case of urinary system infection, 1 case of herpes zoster, 1 case of BK viruria and 2 cases of abnormal blood glucose levels. Conclusions ABOi living-related kidney transplantation may be safely performed by selecting individualized pretreatment regimens according to antibody titers by different blood groups. However, high-dose rituximab or combined use of rabbit anti-human thymocyte immunoglobulin may cause severe infectious complications in highly sensitized recipients.

Clinical trial of low-dose rabbit anti-human thymocyte globulin for induction therapy of kidney transplantation in children / 中华器官移植杂志

Objective:To explore the efficacy and safety of low-dose rabbit anti-human thymocyte globulin (rATG) for induction therapy of kidney transplantation (KT) in children.Methods:From October 2018 to May 2021, clinical data were reviewed retrospectively for 77 pediatric KT recipients on a low-dose rATG induction protocol.Recipient/graft survival rate, renal function recovery, acute rejection (AR) and adverse reactions were observed at 1 year post-operation.The postoperative changes of renal function were examined by Friedman’s test; According to the preoperative baseline data, Pearson’s Chi-square or Fisher's exact test was utilized for examining the influencing factors of postoperative AR.Results:A total of 16(20.78%) recipients had AR within the first 6 months post-operation.The incidence of delayed graft function (DGF) was 14.29%(11/77); The incidence of severe infection post-transplantation 18.18%(14/77), the infection rate of BK virus 25.97%(20/77) and the incidence of neutropenia 32.47%(25/77).The recipient/graft survival rate at 1 year post-operation was 97.40%(75/77) and 94.81%(73/77) respectively.Chi-square test indicated that the incidence of postoperative infection in children with body weight ≤30 kg and height ≤138 cm was 28.95%(11/38) and 27.50%(11/40) respectively, Both were higher than 7.69%(3/39) and 8.11%(3/37) of children with body weight >30 kg and height>138 cm.The difference between groups was statistically significant ( P=0.016 and 0.028). Conclusions:Low-dose rATG is generally excellent in preventing AR in pediatric KT recipients.And the risk of related AR may be lower.The infection rate of recipients with decent preoperative development is low.

Diagnosis and Management of Acquired Aplastic Anemia: Consensus Statement of Indian Academy of Pediatrics

Justification: In India, there is a lack of uniformity of treatment strategies for aplastic anemia (AA), and many children are managed only with supportive care due to non-availability of hematopoietic stem cell transplantation (HSCT). Process: Eminent national faculty members were invited to participate in the process of forming a consensus statement in Hyderabad in July, 2016. Draft guidelines were circulated to all members, and comments received in a online meeting in October, 2020 were incorporated into the final draft. These were approved by all experts. Objective: To facilitate appropriate management of children with acquired aplastic anemia. Recommendations: Key recommendations are: i) A bone marrow biopsy is must to make a diagnosis of AA; ii) Rule out inherited bone marrow failure syndromes (IBMFS), connective tissue disorders, viral infections, paroxysmal nocturnal hemoglobinuria (PNH), drug or heavy metal induced marrow suppression in all cases of AA; iii) Conservative approach to transfusions should be followed, with a target to keep hemoglobin >6 g/dL in children with no co-morbidities; iv) HLA-matched sibling donor HSCT is the preferred choice of treatment for newly diagnosed very severe/ severe AA; v) In absence of HLA-matched family donor, a matched unrelated donor (MUD) transplant or immunosuppressive therapy (IST) should be considered as alternate choice based on physician expertise; vi) Fludarabine, cyclophosphamide and anti-thymocyte globulin (ATG) based conditioning with cyclosporine and methotrexate as graft versus host disease (GvHD) prophylaxis is the preferred regimen; vii) Horse ATG and cyclosporine are the recommended drugs for IST. One should wait for 3-6 months for the response assessment and consideration of next line therapy.

Expression of TOX in mycosis fungoides and its diagnostic value / 中华皮肤科杂志

Objective To assess the value of thymocyte selection-associated high mobility group box (TOX) protein in the diagnosis of mycosis fungoides (MF).Methods Totally,63 paraffin-embedded tissue specimens were collected from Department of Pathology,West China Hospital,Sichuan University between 2003 and 2016,including 30 specimens of suspected MF,23 specimens of confirmed MF and 10 specimens of benign inflammatory dermatoses.Immunohistochemical staining was performed to compare the expression of TOX among groups.Results Twenty-six (86.7％) suspected MF specimens were positive for TOX,20 (87％) confirmed MF specimens,and 3 (30％) benign inflammatory dermatosis specimens were positive for TOX.The positive rate of TOX protein was significantly higher in the suspected MF group and MF group than in the benign inflammatory dermatosis group (both P ＜ 0.05).Conclusions TOX protein was expressed to different extents in the cases of suspected or confirmed MF,and its positive rate was markedly higher in the suspected or confirmed MF group than in the benign inflammatory dermatosis group.TOX protein may act as one of molecular markers for MF.

Similar transplant outcomes between haploidentical and unrelated donors after reduced-intensity conditioning with busulfan, fludarabine, and anti-thymocyte globulin in patients with acute leukemia or myelodysplastic syndrome

BACKGROUND: Although T-cell-replete hematopoietic cell transplantation (HCT) from haploidentical donors (HIDs) using anti-thymocyte globulin (ATG) has shown promising outcomes, previous studies often adopted heterogenous graft sources and conditioning.METHODS: We retrospectively compared HCT outcomes from 62 HIDs, 36 partially-matched unrelated donors (PUDs), and 55 matched unrelated donors (MUDs) in patients with acute leukemia or myelodysplastic syndrome using the same graft source of peripheral blood and a reduced intensity conditioning of busulfan, fludarabine, and ATG.RESULTS: The estimates of 3-yr disease-free survival (DFS) and overall survival (OS) rates were not significantly different among the MUD, HID, and PUD groups, at 46%, “41%, and 36%” for the DFS rate (P=0.844), and 55%, 45%, and 45% for the OS rate (P=0.802), respectively. Cumulative incidence of relapse and non-relapse mortality at 3 yr was similar among different donor types. Subsequent multivariable analyses showed that the sex of the patient (male) and a high/very high disease risk index were independently associated with poorer DFS and OS, while the donor type was not.CONCLUSION: T-cell replete HCT from HIDs using an ATG-containing reduced intensity conditioning regimen may be a reasonable option in the absence of matched related donors in patients with acute leukemia or myelodysplastic syndrome.

Expression of TOX in mycosis fungoides and its diagnostic value / 中华皮肤科杂志

Objective@#To assess the value of thymocyte selection-associated high mobility group box (TOX) protein in the diagnosis of mycosis fungoides (MF) .@*Methods@#Totally, 63 paraffin-embedded tissue specimens were collected from Department of Pathology, West China Hospital, Sichuan University between 2003 and 2016, including 30 specimens of suspected MF, 23 specimens of confirmed MF and 10 specimens of benign inflammatory dermatoses. Immunohistochemical staining was performed to compare the expression of TOX among groups.@*Results@#Twenty-six (86.7%) suspected MF specimens were positive for TOX, 20 (87%) confirmed MF specimens, and 3 (30%) benign inflammatory dermatosis specimens were positive for TOX. The positive rate of TOX protein was significantly higher in the suspected MF group and MF group than in the benign inflammatory dermatosis group (both P<0.05) .@*Conclusions@#TOX protein was expressed to different extents in the cases of suspected or confirmed MF, and its positive rate was markedly higher in the suspected or confirmed MF group than in the benign inflammatory dermatosis group. TOX protein may act as one of molecular markers for MF.

Anti-thymocyte globulin in haematology: Recent developments

Anti-thymocyte globulin (ATG) is a polyclonal antiserum introduced into clinical medicine more than 30 years ago. It induces a broad non-specific immunosuppression. In haematology, standard indications are severe aplastic anaemia and prophylaxis and treatment of graft-versus-host disease (GVHD) (after allogeneic transplantation). For aplastic anaemia, ATG from horses has been found to be superior to ATG from rabbits. In the situation of allogeneic transplantation, ATG lessens the risk of chronic GVHD but may not improve survival. There is current controversy regarding which patients benefit most from ATG and what the ideal dosage is. It is likely that in the coming years a more specific immunosuppressive will be developed that will minimize GVHD while maintaining the graft-versus-malignancy effect.

Effects of DNA methylation of thymocyte differentiation antigen-1 in beryllium sulfate induced human fetal lung fibroblast fibrosis / 中国职业医学

OBJECTIVE: The change of DNA methylation of thymocyte differentiation antigen-1( Thy-1) was observed in beryllium sulfate( Be SO4) stimulated human fetal lung fibroblast( MRC-5 cell) to explore the effects of Thy-1 in Be SO4 induced lung fibrosis. METHODS: MRC-5 cell culture in vitro model was used. The final concentrations of Be SO4were1. 0,10. 0 and 100. 0 μmol / L( low-,medium- and high-dose groups). The control was untreated. Other 2 intervention groups were the 5-azacytidine( AZC) intervention group( 10. 0 μmol / L of AZC and 10. 0 μmol / L Be SO4) and the trichostatin A( TSA) intervention group( 0. 5 μmol / L of TSA and 10. 0 μmol / L Be SO4). The cells were collected 24,48 and 72 hours after exposure. Real-time quantitative polymerase chain reaction( PCR) was used to determine the relative expression of collagen typeⅠ( Col Ⅰ),collagen type Ⅲ( Col Ⅲ),α-smooth muscle actin( α-SMA) and Thy-1 mRNA.The nested landed methylation specific PCR was used to detect the Thy-1 DNA methylation level. RESULTS: At 24 hours,the relative expression level of Col Ⅲ mRNA in MRC-5 cells showed an increasing trend with increasing dose( P < 0. 05);at 48 and 72 hours,the relative expression levels of Col Ⅰ,Col Ⅲ and α-SMA mRNA in MRC-5 cells increased with the increasing dose( P < 0. 05). All these 3 indicators in MRC-5 cells of 3 dose groups increased with the increase of expose time( P < 0. 05). The relative expression level of Thy-1 mRNA in MRC-5 cells of all 3 dose groups were lower than that in control( P < 0. 05). The relative expression level of Thy-1 mRNA of the high-dose group was lower than that of the lowdose group( P < 0. 05). The Thy-1 DNA methylation levels in the medium- and high-dose groups were both higher than that of the control( P < 0. 05). The Thy-1 DNA methylation levels of the 3 dose groups increased with the increasing dose( P < 0. 05). The Thy-1 DNA methylation levels of MRC-5 cells in the 2 intervention groups were higher than that of the control( P < 0. 05),but there was no significant difference when compared with the medium-dose group( P > 0. 05).CONCLUSION: Be SO4 stimulation can induce the fibrosis of MRC-5 cells. In this process,the Thy-1 DNA methylation level increases,while the Thy-1 mRNA expression level decrease. Thy-1 DNA methylation might be one of the important mechanisms of lung fibrosis induced by Be SO4.

Growth hormone in the presence of laminin modulates interaction of human thymic epithelial cells and thymocytes in vitro

BACKGROUND: Several evidences indicate that hormones and neuropeptides function as immunomodulators. Among these, growth hormone (GH) is known to act on the thymic microenvironment, supporting its role in thymocyte differentiation. The aim of this study was to evaluate the effect of GH on human thymocytes and thymic epithelial cells (TEC) in the presence of laminin. RESULTS: GH increased thymocyte adhesion on BSA-coated and further on laminin-coated surfaces. The number of migrating cells in laminin-coated membrane was higher in GH-treated thymocyte group. In both results, VLA-6 expression on thymocytes was constant. Also, treatment with GH enhanced laminin production by TEC after 24 h in culture. However, VLA-6 integrin expression on TEC remained unchanged. Finally, TEC/thymocyte co-culture model demonstrated that GH elevated absolute number of double-negative (CD4-CD8-) and single-positive CD4+ and CD8+ thymocytes. A decrease in cell number was noted in double-positive (CD4+CD8+) thymocytes. CONCLUSIONS: The results of this study demonstrate that GH is capable of enhancing the migratory capacity of human thymocytes in the presence of laminin and promotes modulation of thymocyte subsets after co-culture with TEC.

Acquired amegakaryocytic thrombocytopenic purpura - An underdiagnosed entity.

Acquired Amegakaryocytic Thrombocytopenic Purpura (AATP) is a rare cause of thrombocytopenia presenting over a wide age group with symptoms of bleeding and bone marrow showing isolated absence of megakaryocytes in an otherwise normal marrow. Here, we report a case of AATP in a three year old female child who was then treated with anti thymocyte globulin successfully. We report this case because of it’s under diagnosis or misdiagnosis as immune thrombocytopenia (ITP) in most of the cases. We also review the literature regarding the pathogenesis and treatment of this undiagnosed entity.

Relationship between helper T cell 17/regulatory T cells balance and acute graft versus host disease after allogeneic hematopoieticstem cell transplantation / 中华器官移植杂志

Objective To investigate the relationship between the helper T cell 17 (TH 17)/ Regulatory T cells (Treg cells) balance in peripheral blood with acute graft-versus-host reaction (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT),as well as the impact of anti-thymocyte immunoglobulin (ATG) on helper T cells in peripheral blood.Method Seventyeight hematologic patients underwent allo-HSCT,conditioning with or without ATG.Ten healthy volunteers severed as a control group.The helper T and regulatory T cells in peripheral blood were detected by flow cytometry.Enzyme-linked irnmunosorbent assay (ELISA) was used to detect serum concentrations of interleukin(IL)-17,IL-21,IL22,IL23,γ interferon (IFN-γ),and transforming growth factor β1 (TGF-β1).Result The percentage of Treg cells,TH17 cells and ratio of TH17/Treg cells in patients without aGVHD showed no significant difference from the healthy controls (P＞ 0.05).As compared with control group and non aGVHD group,the ratio of Treg cells was increased,the percentage of TH 17 cells,and TH 17/Treg cells were significantly increased in 1-2-degree aGVHD group (P＜0.01).With increased degree of aGVHD,the difference as above was more significant in 3-4-degree aGVHD recipients (P＜0.01).In aGVHD group,the IL-17,IL-23,IL-21 and IFN-γ concentrations were higher than the healthy group (P＜0.01) and non-aGVHD group (P＜0.05).Serum TGF-β1 level in aGVHD group was significantly decreased as compared with healthy group and non-GVHD group (P＜0.05),while IL-22 concentrations showed no statistically significant difference among three groups (P＞0.05).In anti-thymocyte immunoglobulin (ATG) pretreatment group,the absolute count of peripheral blood lymphocytes was less than in healthy control group (P＜0.01).In ATG group,the absolute counts of TH1 cells,TH17 cells,CD3+ CD4+ cells and non-TH1/17 cells were less than in non-ATG group (P =0.0000),while the absolute counts of lymphocytes,CD3+ CD4-cells,and TH 1/17 cells were less than in non-ATG group,but there was significant difference (P＞0.05).Conclusion The balance of TH 17/Treg cells and related cytokines were closely associated with aGVHD after allo-HSCT,and ATG influences the reconstruction of TH 17 and Th1 cells at early stage.

Outcome of children with severe acquired aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine A, / Resultado de crianças com anemia aplástica grave adquirida tratadas com globulina antitimocítica de coelho e ciclosporina A,

Objective: To evaluate the outcome of children with severe acquired aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine as first-line treatment at this institution. Methods: Retrospective analysis of 26 pediatric patients with aplastic anemia, treated between 1996 and 2011 with rabbit antithymocyte globulin plus cyclosporine. Results: The overall response rate at six months was 34.6% (9/26), and the cumulative incidence of relapse was 26.5% (95% confidence interval [CI]: 1.4%-66%) at 5 years. The cumulative incidence of clonal evolution after immunosuppressive therapy was 8.3% (95% CI: 0.001%-53.7%) at five years with both clonal evolutions in non-responders who acquired monosomy 7 karyotype. The overall survival at five years was 73.6% (95% CI: 49.2%-87.5%). Conclusions: The present results confirm the poor response rate with rabbit antithymocyte globulin as first therapy in pediatrics patients, similar to what has been reported for patients of all ages. This confirmation is problematic in Brazil, given the lack of horse antithymocyte globulin in many markets outside the United States. .

Objetivo: Avaliar o resultado de crianças com anemia aplástica grave adquirida tratadas com globulina antitimocítica de coelho e ciclosporina como tratamento inicial em nosso instituto. Métodos: Análise retrospectiva de 26 pacientes pediátricos com anemia aplástica tratados entre 1996 e 2011 com globulina antitimocítica de coelho e ciclosporina. Resultados: A taxa de resposta geral em seis meses foi de 34,6% (9/26), e a incidência acumulada de recorrência foi de 26,5% (intervalo de confiança [IC] de 95%,1,4%-66%) em cinco anos. A incidência acumulada de evolução clonal após a terapia imunossupressora foi de 8,3% (IC 95%, 0,001%-53,7%) em cinco anos, com ambas as evoluções clonais em pacientes sem resposta que adquiriram o cariótipo com monossomia 7. A sobrevida geral em cinco anos foi de 73,6% (IC 95%, 49,2%-87,5%). Conclusões: Nossos resultados confirmam a baixa taxa de resposta com globulina antitimocítica de coelho como terapia inicial em pacientes pediátricos, da mesma forma como relatado para pacientes de todas as idades. Essa confirmação é problemática em nosso país devido à falta de globulina antitimocítica de cavalo em muitos mercados fora dos Estados Unidos, incluindo o Brasil. .

Effects of ionizing radiation on expression of P21 protein in Jurkat cell line and p21 gene in thymocytes and splenocytes of mice / 中华放射医学与防护杂志

Objective To investigate the effects of ionizing radiation on the expression of P21 protein in Jurkat cell line and p21 gene in thymocytes and splenocytes of mice.Methods Flow cytometry (FCM)was used to analyze the expression of P21 protein in Jurkat cells at 12 and 24 h after irradiation to 0,0.5,1.0,2.0,4.0,and 6.0 Gy.Real-time PCR was used to detect the expression of p21 gene in thymocytes and splenocytes of mice at4 and 24 h after irradiation to 0,0.5,1.0,2.0,4.0,and 6.0 Gy.Multi-staining was used to analyze the micronucleus rates of Rct in bone marrow.Results The expressions of P21 protein were increased in a dose-dependent manner during 0.5-4.0 Gy(t=-24.23--3.96,P<0.05),but decreased at 6.0 Gy at 12 and 24 h post-irradiation(t=-11.19,-14.50,P<0.05).The expressions of p2 1 gene in both thymocytes and splenocytes of mice were increased in dose-dependent manner in the range of 0-6.0 Gy(including 6.0 Gy)(t=-29.96-8.80,P<0.05),and reached to the peak at 6.0 Gy at 4 and 24 h post-irradiation(t=-11.84--3.42,P<0.05),except thymocytes at 4 h and 1.0 Gy post-irradiation(t=-3.42,P>0.05).Conclusions The expressions of P21 protein and p21 gene could be increased by X-ray irradiation.which shows good dosedependent manners in certain range of dose.

Effects of pneumonia caused by klebsiella pneumoniae on apoptosis of thymocytes in rats / 中华急诊医学杂志

Objective To study the effects of pneumonia caused by Klebsiella pneumoniae on apoptosis of thymocytes in rats and its possible mechanism. Methods A total of 48 Sprague Dawley rats were randomly (random number) divided into 2 groups, namely the control group (n =24) and the infection group ( n = 24). The pneumonia models of rats were made with 0.3 mL Klebsiella pneumoniae suspension administered intratracheally per animal. On the 2nd, 4th, and 6th day after intratracheal instillation of bacteria, 1/ 3 of the rats in each group were sacrificed and TdT-mediated dUTP nick end labeling (TUN EL) method was used to assess the apoptosis of thymocytes. The expressions of cleaved Caspase-3, Bcl-2 and Fas in thympcytes of rats were detected with immunohistochemical staining. Results On each interval, apoptosis index of thymocytes, and the expressions of Cleaved Caspase-3 and Fas in the infection group were all higher than those in the control group (P < 0.01) , while the expressions of Bcl-2 lower than those in the control group (P<0.01). As more time consumed, the apoptotic index of thymocytes and the expressions of cleaved Caspase-3 in the infection group increased significantly (P<0.05). The expressions of Bcl-2 declined gradually (P < 0.05), but the expressions of Fas reached their peak 4th day after infection. There were no significant dynamic changes in all above mentioned variables in control group. Conclusions Pneumonia caused by Klebsiella Pneumoniae can lead to the increase in thymocyte apoptosis in rats. The mechanism may be associated with the decreased expression of Bcl-2 and the increased expression of Fas in thymocytes of rats with pneumonia caused by Klebsiella pneumoniae. The different apoptosis regulation pathways have different effects on different phase of pneumonia, that the effects of Fas decrease 4th day after pneumonia, while the effects of Bcl-2 increase further.

Glucocorticoids, master modulators of the thymic catecholaminergic system?

There is evidence that the major mediators of stress, i.e., catecholamines and glucocorticoids, play an important role in modulating thymopoiesis and consequently immune responses. Furthermore, there are data suggesting that glucocorticoids influence catecholamine action. Therefore, to assess the putative relevance of glucocorticoid-catecholamine interplay in the modulation of thymopoiesis we analyzed thymocyte differentiation/maturation in non-adrenalectomized and andrenalectomized rats subjected to treatment with propranolol (0.4 mg·100 g body weight-1·day-1) for 4 days. The effects of β-adrenoceptor blockade on thymopoiesis in non-adrenalectomized rats differed not only quantitatively but also qualitatively from those in adrenalectomized rats. In adrenalectomized rats, besides a more efficient thymopoiesis [judged by a more pronounced increase in the relative proportion of the most mature single-positive TCRαβhigh thymocytes as revealed by two-way ANOVA; for CD4+CD8- F (1,20) = 10.92, P < 0.01; for CD4-CD8+ F (1,20) = 7.47, P < 0.05], a skewed thymocyte maturation towards the CD4-CD8+ phenotype, and consequently a diminished CD4+CD8-/CD4-CD8+ mature TCRαβhigh thymocyte ratio (3.41 ± 0.21 in non-adrenalectomized rats vs 2.90 ± 0.31 in adrenalectomized rats, P < 0.05) were found. Therefore, we assumed that catecholaminergic modulation of thymopoiesis exhibits a substantial degree of glucocorticoid-dependent plasticity. Given that glucocorticoids, apart from catecholamine synthesis, influence adrenoceptor expression, we also hypothesized that the lack of adrenal glucocorticoids affected not only β-adrenoceptor- but also α-adrenoceptor-mediated modulation of thymopoiesis.

Interaction between the mouse homologue of CD99 and its ligand PILR as a mechanism of T cell receptor-independent thymocyte apoptosis

Here, we show that the interaction between two membrane proteins, the mouse homologue of CD99 (designated D4) and its ligand, paired immunoglobulin-like type 2 receptor (PILR), is one of the major mechanisms of thymocyte apoptosis. Using the polymeric fusion protein of PILR and IgG1 (PILR-Ig), we demonstrated that D4 ligation in the absence of T cell receptor (TCR) engagement leads to the induction of apoptosis, mainly at the double-positive stage of thymocytes. This was further confirmed by a blocking study in which blocking the interaction between D4 and PILR by soluble D4 protein led to reduced apoptosis in the fetal thymic organ culture with wild type and TCRalpha(-/-) mice. Furthermore, the dissection of intracellular signaling pathway demonstrated that D4 cross-linking led to caspase activation without any change in mitochondrial membrane potential. Based on these data, we propose a mechanism for thymocyte depletion in which the interaction between D4 and PILR delivers an active signal.

Allogeneic Hematopoietic Cell Transplantation from an HLA-mismatched Family Donor: The Current Status and Future

Traditionally, human leukocyte antigen (HLA)-mismatched hematopoietic cell transplantation (HCT) has been considered ill-advised in a routine clinical practice due to excessive serious post-transplant complications, such as graft failure, graft-versus-host disease, and prolonged immunosuppression resulting in increased fatal infections. Recent introduction of new HCT techniques, especially in the area of conditioning therapy, has improved outcomes of HLAmismatched HCT considerably. Using several regimens of reduced-intensity conditioning (RIC), it is now possible to perform allogeneic HCT in patients without HLA-matched donors in the family or in the registry from HLA-mismatched family donors. Furthermore, due to less rigorous nature of RIC therapy, elderly patients (up to 70 years of age) and patients who have been treated heavily especially with a previous HCT can also be treated. In this review, we gave a brief historical background for the development of allogeneic HCT, discussed rationale for the use RIC for HLA-mismatched HCT, and summarized trial results of HLA-mismatched HCT after RIC. Lastly, future areas of research regarding HLA-mismatched HCT were discussed.

Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats

The role of gonadal hormones in induction and, particularly, maintenance/progression of rat thymic involution, which normally starts around puberty, was reassessed by examining the effects of peripubertal orchidectomy on thymic weight and morphometric parameters at different times up to the age of 10 months. Up to 6 months post-castration both thymic weight and cellularity in orchidectomized (Cx) rats were greater than in age-matched control rats, sham Cx (Sx). The increase in thymic cellularity reflected an increase in thymocyte proliferation rate (the proportion of proliferating cells was 18.6 ± 0.7 percent in 2-month-old Cx (N = 5) vs 13.4 ± 0.3 percent (N = 5) in age-matched Sx rats) followed by reduced sensitivity to apoptotic signals (apoptotic thymocytes were 9.8 ± 0.9 percent in 2-month-old Cx (N = 5) vs 15.5 ± 0.3 percent (N = 5) age-matched Sx rats). However, 9 months post-orchidectomy, neither thymic weight and cellularity nor any of the morphometric parameters analyzed differed between Cx and control rats. The reduction of thymic cellularity in Cx rats to control values may be related to increased sensitivity of their thymocytes to apoptotic signals in culture (72.6 ± 1.2 percent in 10-month-old vs 9.8 ± 0.9 percent in 2-month-old Cx rats) followed by reduced responsiveness to proliferative stimuli (14.1 ± 0.2 percent in 10-month-old vs 18.6 ± 0.7 percent in 2-month-old Cx rats). Thus, the study indicates that the effects of peripubertal orchidectomy on thymic weight and cellularity, as well as on the main morphometric indices, are long-lasting but not permanent, i.e., that removal of the testes can only postpone but not prevent age-related organ atrophy and consequently functional deterioration of the immune system.

A Case of C4d-Positive Acute Humoral Rejection Treated with Rituximab and Plasma Exchange / 대한신장학회잡지

Although acute humoral rejection is a major cause of renal allograft loss, the diagnosis and treatment of acute humoral rejection have been very difficult because of lack of proper diagnostic tools and effective therapeutic modalities. Recently C4d deposition in peritubular capillaries of renal allografts has been demonstrated to be a sensitive and diagnostic in-situ marker of humoral rejection that correlates strongly with the presence of circulating donor-specific antibodies. Whereas conventional immunosuppressive agents are effective for the treatment of cellular rejection, specific therapeutic strategies targeting the humoral limb of immunosuppression should be necessary for the treatment of humoral rejection. Here we report a case of acute humoral rejection diagnosed with C4d immunostaining from transplant kidney biopsy and treated successfully with combination of plasma exchange, polyclonal rabbit anti-thymocyte globulin, and rituximab.

Mechanism ud protection of electro-acupuncture at Zusanli points(足三星穴) on the apoptosis of thymocytes in rats with severe abdominal infection / 中国中西医结合急救杂志

Objective To study the influence of electro-acupuncture(EA)at Zusanli points(足三里穴) on the apoptosis of thymocytes in rats with abdominal infection and its mechanism.Methods A total of 40 Sprague-Dawley(SD)rats were randomly divided into four groups,including normal control group,model group,non-acupoint group and Zusanli group.The abdominal infection model of rat was made by cecal ligation and puncture(CLP).After abdominal cavity infection for 36 hours,the apoptosis of thymocytes was observed under electron microscope and light microscope,and the apoptosis ratio of thymocytes was determined by Annexin V-PI method with flow cytometry technique.The content of Bcl-2 protein of thymocytes and concentration of corticosterone in plasma were determined.Results Abdominal infection resulted from CLP could significantly increase the apoptosis of thymocytes and lead to the typical histopathological changes of apoptosis of thymocytes under electron microscope and light microscope.Apoptosis ratios of thyrnocytes in model group[(44.7?3.3)%],non-acupoint group[(42.7?3.0)%]and Zusanli group[(32.6?3.3)%] were significantly higher than the ratio in the control group[(21.2?2.3)%,all P0.05).Abdominal infection resulted from CLP also could reduce the content of Bcl-2 protein of thymocytes.The content of Bcl-2 protein of thymocytes in model group(71.2?5.6),non-acupoint group(73.5?5.9)and Zusanli group(82.4?6.8) were significantly lower than normal control group(95.3?6.3,all P