Features of acquired immune properties in innate immune cells and its roles in transplant rejection / 中华消化外科杂志

Transplant rejection involves natural immune cells and acquired immune cells. For decades, acquired immune cells have been dominating the study of transplant immunity. Researchers have found the surprising new features of innate immune cells, including immune memory, which may be of great significance to further improve graft survival. The short-term survival rate of grafts is very good, but the long-term graft outcomes are less so and most transplants are eventually lost to chronic rejection in the clinic. In animal models and clinical studies, innate immune cells, especially macrophages and natural killer cells, often predominate the chronic rejection process which lead grafts lost. Recent studies suggest that innate immune cells are capable of acquiring adaptive features in that they either directly recognize the allografts or become "trained" in the allogeneic milieu to further acquire features of memory and donor specificity. In selected transplant models, targeting the adaptive features of innate immune cells has been shown to promote long-term graft survival. Clearly, these findings highlight new therapeutic opportunities in further improvement of transplant outcomes as well as in treatment of cancers and autoimmune diseases in the clinic. The authors summarize the literature reports, introduce the recent acquired response characteristics of natural immune cells, and stimulate researchers to carry out more exploration in this field by fully discussing the heterogeneity and plasticity of natural immune cell types and the outstanding problems in related field.

Recent advances of exosomes in immune-mediated eye diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Immune-mediated eye diseases(IMED)represent a kind of autoimmune eye diseases, such as thyroid-associated ophthalmopathy, autoimmune uveitis and Sjögren syndromes. Owning to its complicated pathophysiological mechanisms, the efficacies of current therapeutic strategies for IMED are unsatisfactory, which may ultimately result in severe visual impairment. Exosomes are lipid bilayer vesicles secreted by cells that play an important role in cell-to-cell communication and immune regulation. Recent studies have shown that exosomes secreted by cells under pathological conditions are closely associated with the development and progression of IMED, and the exosomes derived from certain cells(such as mesenchymal stem cells)are deemed as promising therapy for IMED. Hence, we review the recent advances of exosomes in IMED.

Qualidade de vida de pacientes que retornam a Hemodiálise após serem submetidos a um transplante renal / Quality of life of patients returning hemodialysic after submitting a renal transplant

Introdução: A Doença Renal Crônica (DRC) é caracterizada pela perda gradual e irreversível da função renal, esse fato ocorre quando os rins deixam de remover os produtos metabólicos produzidos pelo corpo ou de realizar sua função reguladora. O transplante renal envolve transplantar o rim de um doador vivo ou falecido para um receptor que não apresenta mais função renal. Objetivo: Avaliar a qualidade de vida de pessoas que retornaram a hemodiálise após transplante renal. Métodos: Pesquisa de abordagem qualitativa, do tipo estudo de caso. Utilizou-se de uma entrevista semiestruturada e o instrumento de avaliação de qualidade de vida da Organização Mundial de Saúde, WHOQOL-100.Foram entrevistadosdois pacientes, recrutados por meio do contato com o serviço de Nefrologiaonde os mesmosrealizavam o tratamento dialítico.Resultados: A entrevista demonstrou que o diagnóstico de rejeição do órgão é um dos momentos mais difíceis para o paciente, a assistência da família durante o tratamento é de fundamental importância, as restrições dietéticas e hídricas tornam-se uma carga a mais durante o tratamento e as expectativas futuras possivelmente serão menores considerando a fase da vida em que esse diagnóstico é constatado. No WHOQOL-100, os entrevistados apresentam níveis iguais ou acima da média de qualidade de vida, sendo apenas o domínio de nível de independência odemenor escore. Conclusão: A pesquisa enfatiza a necessidade de uma atenção profissional humanista e acolhedora, visto que esse retorno a hemodiálise após passar pelo transplante pode ocasionar um impacto negativo nas dimensões físicas, psíquicas e sociais das pessoas que voltam a realizar hemodiálise (AU).

Introduction: Chronic Kidney Disease (CKD) is characterized by the gradual and irreversible loss of renal function,this occurs when the kidneys fail to remove the metabolic products produced by the body or to perform its regulatory function. Kidney transplantation involves transplanting the kidney from a living or deceased donor to a recipient who has no kidney function.Objective: To evaluate the quality of life of people who returned to hemodialysis after a kidney transplant.Methods: Qualitative research, case study type. It used a semistructured interview and the assessment tool of quality of life of the World Health Organization, WHOQOL-100.Two patients were interviewed, recruited through contact with the Nephrology service where they performed the dialysis treatment.Results: The interview demonstrated that the diagnosis of rejection of the organ is one of the most difficult moments for the patient, the family assistance in treatment is of fundamental importance, dietary and water restrictions become overloaded during the treatment and the future expectations possibly will be smaller considering the stage of life in which the diagnosis is established. The WHOQOL100, the interviewees feature levels equal to or above the average quality of life, being only the domain of independence level with the lowest score.Conclusion: The research emphasizes the need for a professional humanist and friendly attention, Since this return to dialysis after passing by the transplant can cause a negative impact on physical, psychological and social dimensions, of the people who come back to perform hemodialysis (AU).

Study on the effect of γδT cell activated in mice islet transplantation rejection / 重庆医学

Objective After the islet transplantation,observed blood glucose and survival time in the islet transplantation mice model to explore the effect of intestinal epithelial γδT cell in islet transplantation rejection.Methods Established the mice model of islet transplantation,divided into wild type mice group,γδ gene knockout mice group and γδ gene knockout γδT cell reinfusion mice group,observed blood glucose in 1,3,5,7,9,11,13,15,17,19,21,23,25,27,29 days after surgery and pathological conditions aft er two weeks of transplantation.Results After transplantation,the rising blood glucose of wild type mice group and γδ gene knockout γδT cell reinfusion mice group were significantly slower than that of γδ gene knockout mice group (P＜0.05),but there was no significant difference in between two groups (P＞0.05).The survival time of wild-type mice group was (27±2) days,and γδ gene knockout γδT cell reinfusion mice group was (24±1) days,they were significantly longer than (17±3) days of γδ gene knockout mice group (P＜ 0.05).Conclusion As a special kind of T cells,γδT intestinal epithelial cell plays an important role in the islet transplantation rejection.

The Role of B Cells in Transplantation Rejection / 대한이식학회지

B cells play a role in graft rejection via several mechanisms. Specifically, B cells produce high-affinity antibodies to alloantigens including allogeneic major histocompatibility complex (MHC) with the help of follicular helper T cells. B cells also function as antigen-presenting cells for alloreactive T cells, resulting in the activation of alloreactive T cells. Conversely, the frequency of regulatory B cells increases under inflammatory conditions and suppresses the rejection process. Here, the differential roles of the major B cell subpopulations (B-1, follicular B, marginal zone B, and regulatory B cells) involved in transplantation rejection are discussed together with their interaction with T cells.

Prevalence of Erythrocytopenia & Thrombocytopenia in Eastern Indian Population & its Correlation with Acute Antibody Mediated Renal Transplant Rejection & Cytomegaloviral Nephropathy.

Objective: Our objective was to study the prevalence of thrombocytopenia & erythrocytopenia post renal transplantation in Eastern Indian population. Thrombocytopenia & erythrocytopenia are common phenomena prevailing post transplant rejection. It is found to occur in patients developing HCMV (human cytomegaloviral nephropathy), post transplantation. Whereas in the case of none rejected patients thrombocytopenia is unlikely to occur. Methods: Several methodologies such as the serological cross match, HLA-cross match DSA luminex, renal biopsy including C4d staining, hematological RBC & platelet count monitoring were adopted in the study, along with these the serum creatinine levels of the rejected patients were tested by making use of several biochemical approaches. Statistical analysis of the data obtained from the laboratories, were also done by the software prism 4.1. Results: Out of total population of 30 patients selected randomly, 24 were found to have successful transplants as for them a significant increase in both platelet & RBC count were noticed post transplantation where as for the other 6 patients a significant decrease in the RBC & platelet count was observed post transplantation along with a significant increase in the serum creatinine levels. There was also a significant decrease in the GFR (glomerular filtration rate) which was an indication of some sort of graft dysfunctioning. All the patients were checked for viral nephropathy & the above 6 patients were found to develop HCMV nephropathy. For the above mentioned 6 patients, the presence of C4d marker in their renal peritubular capillaries after performing the immunehistochemical C4d staining was a key indicator of acute antibody mediated rejection. Conclusion: Our study clearly reveals that Thrombocytopenia & erythrocytopenia was quite common in the patients with acute antibody mediated renal transplant rejection. A low RBC & platelet count persisted in them even after transplantation owing to allograft rejection, & HCMV nephropathy. Whereas for the patients with successful transplants events such as thrombocytopenia & erythrocytopenia were nevertheless unlikely.

Role and its mechanism of immature dendritic cells with IL-10 gene modified in rats after keratoplasty / 国际眼科杂志(Guoji Yanke Zazhi)

Abstract? AIM: Through the establishment of penetrating keratoplasty model of rats, to detect the role and its mechanism of immature dendritic cells with IL-10 gene modified.? METHODS: Allogeneic penetrating corneal transplantation in rat model was performed. SD rats were randomly divided into positive control group, GFP-DC group, 8-DC and IL-10-GFP-DC group.At 3d before keratoplasty, the rats were given tail intravenous injection with the same amount of PBS, bone marrow 8-DC ( DC had cultured for 8d ) from donor Wistar rats, GFP-DC after 48h transfection and IL-10-GFP-DC.Rats were observed under slit-lamp for corneal graft cases every day, and recorded rejection index and corneal graft survival time.At 14d after keratoplasty, pathologic and immunohistochemical examinations were performed.?RESULTS:Compared with GFP-DC group and 8-DC group, corneal graft survival time of IL-10-GFP-DC group was significantly longer ( P<0.01 ); at 14d after keratoplasty, corneal opacity, edema, neovascularization and rejection index of IL-10 -GFP-DC group were significantly lower (P<0.01).Pathological examination showed that in the three experimental groups corneal inflammation was lighter than the positive control group without significant central graft neovascularization. Immunohistochemistry showed: compared to the positive control group, GFP-DC group and 8-DC group, CD4+, CD8+, CD25+, IL-2+, NK+and NF-κB+positive cells in IL-10-GFP-DC group were lower(P<0.01).? CONCLUSION: After donor -derived immature dendritic cells pretreated, corneal graft survival was significantly prolonged, successfully induced corneal transplantation tolerance. CD4+, CD8+, CD25+, IL-2+, NK+and NF-κB+positive cells are involved in corneal allograft rejection regulation, IL-10-GFP-DC may reduce CD4+, CD8+, CD25+, IL-2+, NK+and NF-κB+positive cell infiltration, inhibit corneal transplant rejection.

Evaluation of acute rejection after liver transplantation with acoustic radiation force impulse and color Doppler flow imaging / 中华超声影像学杂志

Objective To investigate the value of acoustic radiation force impulse (ARFI)and color Doppler flow imaging (CDFI)in the diagnostic of acute rejection (AR)after liver transplantation.Methods B mode ultrasound,CDFI and ARFI exams were performed on fifty-eight patients who was diagnosed with AR through liver biopsy in our hospital.The liver allograft size,mean velocity of portal vein,hepatic vein spectrum waveform and shear-wave velocity were obtained and compared with the results of 30 healthy subjects as control group.Results Compare to control group,the AR group had a significant increase in liver allograft,decrease in mean velocity of portal vein,the elimination of triphasic wave of hepatic vein,and a significant increase in shear-wave velocity (P =0.000,0.000,0.007,0.000,respectively).The correlation coefficient between four criteria and grouping was 0.478,0.557,0.286,0.483,respectively.The area under ROC curves for diagnosing AR using the four criterias mentioned above was 0.914.Conclusions Combination of CDFI and ARFI in diagnosing of AR after liver transplantation has higher sensitivity and accuracy.

Immunosuppressive function of histone deacetylases inhibitors: Recent progress / 第二军医大学学报

Histone deacetylases inhibitors (HDACIs) are a group of compound regulating gene expression at transcriptional level. HDACIs can induce protein hyperacetylation and subsequently lead to chromatin remodeling, cell-cycle arrest, cell differentiation and apoptosis, and transcriptional activation and repression. HDACIs demonstrate promising antitumor activity and are presently tested in clinical studies for solid and hematologic malignancies. Cumulating evidence in animal models of immune disorders also suggests immunosuppressive properties of HDACIs, which provides us with new ideas for treating immune disorders and rejection after transplantation. This paper reviews the recent progress of immunosuppressive function induced by HDACIs from the following aspects: immune diseases, T lymphocytes, inflammatory cytokines and dendritic cells.

Is Serum Transforming Growth Factor beta-1 Superior to Serum Creatinine for assessing Renal Failure and Renal Transplant Rejection.

A sustained overexpression of Transforming Growth Factor beta1 (TGF beta1), a cytokine has been implicated in the pathogenesis of fibrosis of kidney leading to end stage . The main aim of present study was to find the utility of TGF beta1 and serum creatinine in differentiating chronic renal failure (CRF) from acute renal failure (ARF), renal transplant rejection (Tx Rej) and stable renal transplant (Tx Stb) and to study has attempted histopathological correlation of rejection cases with TGF beta1 and serum creatinine. TGF beta1 was determined by using ELISA and serum creatinine was done by autoanalyser. In normal healthy controls (NHC), in majority of cases (80.0%) TGF beta1 was below 25 ng/ml while in 6.0% cases it was upto 34 ng/ml. Rise of TGF beta1 was significant in CRF patients as compared to ARF and NHC (p<0.05) .In rejection cases, TGF beta1 level was significantly raised as compared to NHC and stable graft cases (p<0.05). In rejection cases, it was raised above 40 ng/ml in only 50% cases. In two cases inspite of more than 70% glomerular fibrosis, the patient had TGF beta1 level of only 5 ng/ml and in other three cases of acute cellular rejection the level was 70, 35 and 28 ng/ml respectively.Contrary to it serum creatinine was raised above 2 mg/dl in all cases of transplant rejection but in stable transplant cases in majority (70.6%) it was below 1.5 mg/dl and in 5 cases it was between 1.5 – 1.9 mg/dl.Thus the study suggests that TGF beta1 may not be a good marker for chronic transplant rejection, as it does not correlate well with glomerular fibrosis, probably it is more associated with interstitial inflammation but it can differentiate CRF from ARF if cut off of 40 ng/ml is taken.

A clinical analysis of HLA-identical hematopoietic stem cell transplantation for severe aplastic anemia / 中华内科杂志

Objective To study the outcome of HLA-identical hematopoietic stem cell transplantation ( HSCT) for severe aplastic anemia (SAA). Methods Twenty patients diagnosed with SAA received allogeneic HSCT from HLA-identical donors ( 17 from siblings and 3 from unrelated donors) between January 2000 and November 2008. Conditioning regimen consisted of cyclophosphamide ( Cy) and anti-thymocyte immunoglobulin (ATG). The patients were administrated with G-CSF-primed bone marrow (G-BM) and mobilized peripheral blood (G-PB) as grafts from the sibling donors or only G-PB from the unrelated donors. Results The median infused number of mononuclear cells and CD_(34)~+ cells were 7. 89 (4-14.21) × 10~8/kg and 2.60 (0.81-4.45) × 10~6/kg. All the patients got engraftment with 100% donor chimerism. The median time of neutrophil and platelet engraftment were 14 ( 11-20) d and 12 (8-108 )d respectively. The cumulative incidence rate of acute GVHD at 100 d was 16% (grade I : 3 cases,grade II :3 cases). Chronic GVHD occurred in 7 of the 19 evaluable cases (4 limited, 3 extensive). Till February 28, 2009, with a median follow-up of 18 months, 17 patients were alive and the overall survival rate was 82. 5%. Conclusion The study confirms that using G-PB with or without G-BM as graft after Cy + ATG conditioning results in excellent outcome of HLA-identical HSCT in patients with SAA.

Current Status and Future Perspectives of Xenotransplantation / 대한이식학회지

Xenotransplantation using pigs as the transplant source holds great promise to resolve the severe shortage of human organ donors. Although stem-cell-derived organ and tissue regeneration have a potential to solve this as well for the future, it still remains as very early experimental phase. Likewise, artificial organs and mechanical devices have been simply used for bridge therapy to transplant. Therefore, xenotransplantation might provide the most imminent solution to the scarcity of human organ donors. In the last two decades, major progress has been made in understanding the mechanisms of xenografts rejection, zoonotic infections including porcine endogenous retrovirus (PERV) and production of genetically engineered pigs including alpha1,3-galactosyltransferase-deficient pigs. With these elaborations, it is now on the threshold of first clinical application. Particularly promising first target is porcine pancreatic islet xenotransplantation. Graft survival has been prolonged to almost one year in the non-human primate study and is waiting for the development of relatively non-toxic or clinically applicable immunosuppressive or tolerance-inducing regimens. This review highlights the currently known obstacles to translate xenotransplantation into clinical therapies and the possible strategies to overcome these hurdles, as well as current status and future perspective for clinical xenotransplantaion.

Observations on acute rejection reaction of orthotopic liver transplantation in Wistar-SD rats / 中国普通外科杂志

Objective To observe the manifestations and judgement methods of acute rejection reaction of orthotopic liver transplantation in Wistar-SD rats.Methods The survival conditions after operation in rats was observed,and liver function tests and histopathology examination were used to study the manifestations of acute rejection reaction of orthotopic liver transplantation in Wistar-SD rats.Results Wistar-SD experiment group had moderate to severe acute rejection reaction after OLT.Alanine aminotransferase,aspartate aminotransferase,total bilirubin io clood serum after orthotopic liver transplantation in rats was obviously elevated on 1-3 d and 7 d after OLT,which are significantly different from every corresponding time point of control group(P

Immunosuppressive function of histone deacetylases inhibitors:recent progress / 第二军医大学学报

Histone deacetylases inhibitors(HDACIs)are a group of compound regulating gene expression at transcriptional level.HDACIs can induce protein hyperacetylation and subsequently lead to chromatin remodeling,cell-cycle arrest,cell differentiation and apoptosis,and transcriptional activation and repression.HDACIs demonstrate promising antitumor activity and are presently tested in clinical studies for solid and hematologic malignancies.Cumulating evidence in animal models of immune disorders also suggests immunosuppressive properties of HDACIs,which provides us with new ideas for treating immune disorders and rejection after transplantation.This paper reviews the recent progress of immunosuppressive function induced by HDACIs from the following aspects:immune diseases,T lymphocytes,inflammatory cytokines and dendritic cells.