器官移植

Reflection on 10 problems of clinical xenotransplantation

Dou Kefeng, Zhang Xuan

2022, 13(4): 411-416. doi: 10.3969/j.issn.1674-7445.2022.04.001

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Abstract:
The shortage of donors restricts the development of organ transplantation. Xenotransplantation might act as an effective approach to resolve this problem. With the advancement of genome editing technologies as well as research and development of novel immunosuppressant, lots of breakthroughs have been achieved in the field of xenotransplantation. Nevertheless, a majority of researches are still in the preclinical stage. Recently, the success of the world's first genetically engineered pig-to-human heart transplantation has greatly inspired researchers. However, clinical xenotransplantation still faces an array of problems, including counteracting rejection, controlling inflammation, regulating coagulation disorder, improving physiological compatibility of xenografts, paying attention to the risk of interspecific infection, optimizing immunosuppressive regimen, screening donor genome editing types, selecting suitable recipients, modifying xenotransplantation guidelines, and awareness of public recognition, etc. In this article, these 10 problems were summarized, aiming to provide reference for promoting the clinical application of xenotransplantation.

Current status and prospect of global development of lung transplantation

Jiao Guohui, Wang Zitao, Chen Jingyu

2022, 13(4): 417-424. doi: 10.3969/j.issn.1674-7445.2022.04.002

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During the novel coronavirus pneumonia (COVID-19) pandemic from 2020 to 2021, lung transplantation entered a new stage of development worldwide. Globally, more than 70 000 cases of lung transplantation have been reported to the International Society for Heart and Lung Transplantation (ISHLT). With the development of medical techniques over time, the characteristics of lung transplant donors and recipients and the indications of pediatric lung transplantation recipients have undergone significant changes. Application of lung transplantation in the treatment of COVID-19-related acute respiratory distress syndrome (ARDS) has also captivated worldwide attention. Along with persistent development of lung transplantation, it will be integrated with more novel techniques to make breakthroughs in the fields of artificial lung and xenotransplantation. In this article, research progresses on the characteristics of lung transplant donors and recipients around the world were reviewed and the development trend was predicted, enabling patients with end-stage lung disease to obtain more benefits from the development of lung transplantation technique.

Diagnostic criteria and research progress on Banff classification of allograft pathology in composite tissue allotransplantation

Xiong Yan, Ye Qifa, Kong Fanhua, Guo Hui

2022, 13(4): 425-433. doi: 10.3969/j.issn.1674-7445.2022.04.003

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Composite tissue allotransplantation (CTA) is a novel transplantation discipline to treat functional tissue or limb defects. Since a majority of CTA grafts were vascularized grafts, it is also known as vascularized composite allotransplantation (VCA). The grafts of CTA/VCA consist of two or more types of allogeneic skin, subcutaneous tissue, bone, muscle, nerve and vessel, etc. Most of CTA/VCA grafts contain skin tissues, which possess the highest antigenicity. Acute rejection after transplantation is the primary obstacle leading to CTA/VCA graft failure and primary graft dysfunction. Hence, histopathological characteristics of skin rejection in CTA/VCA grafts have become the primary hotspot. In this article, pathological features of CTA/VCA rejection, Banff classification in 2007 and related research progress were reviewed, aiming to provide reference for the diagnosis and treatment of rejection and other complications of CTA/VCA.

Research progress on kidney transplantation in HIV-positive patients

Han Fei, Huang Zhengyu

2022, 13(4): 434-439. doi: 10.3969/j.issn.1674-7445.2022.04.004

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Patients infected with human immunodeficiency virus (HIV) are prone to renal insufficiency, which may progress into end-stage renal disease (ESRD). HIV infection has been previously considered as an absolute contraindication of transplantation. The lives of HIV-positive ESRD patients can only maintained through dialysis. With the development of medicine, transplantation practitioners at home and abroad attempt to perform kidney transplantation in HIV-positive patients. Whether kidney transplantation is feasible for HIV-positive patients, whether HIV-positive donor kidneys can be used for transplantation, and the efficacy of kidney transplantation for HIV-positive patients has always been hot topics in the field of transplantation. In this article, HIV-associated nephropathy, the conditions of kidney transplantation for HIV-positive patients, the efficacy of kidney transplantation for HIV-positive patients, use of HIV-positive donor kidneys, use of immune-inducing drugs and postoperative use of immunosuppressants for HIV-positive patients were illustrated, aiming to provide reference for kidney transplantation for HIV-positive patients in clinical practice, application of HIV-positive donor kidneys and postoperative management of HIV-positive patients.

Organ transplantation and parasitic infection

Ye Junsheng

2022, 13(4): 440-447. doi: 10.3969/j.issn.1674-7445.2022.04.005

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Parasitic infection is manifested with the characteristics of both endemic and infectious diseases, and the onset of parasitic infection is regional and infectious. The incidence of parasitic infection after organ transplantation is relatively low, primarily occurring in single case or case series in developing countries and regions. With the development of social economy and a gradual increasing number of organ transplantation, the risk of parasitic exposure is increased when the recipients travel among different countries or regions. In addition, immunosuppression is the risk factor of parasitic infection. Consequently, the risk of parasitic infection in organ transplant recipients cannot be ignored. In this article, epidemiological characteristics, clinical manifestations, diagnosis, treatment and prevention of parasitic infection after organ transplantation were classified and summarized according to literature review, aiming to provide reference for the prevention and treatment of parasitic infection in organ transplant recipients.

Prevention and treatment of fungal infection after solid organ transplantation

Deng Feiwen

2022, 13(4): 448-454. doi: 10.3969/j.issn.1674-7445.2022.04.006

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Over nearly 70-year development, organ transplantation has become an effective treatment for multiple end-stage diseases. However, postoperative administration of immunosuppressants should be given for the recipients, which leads to low immune function and high incidence rate of infection, including viral, bacterial and fungal infections. Among them, the occurrence of fungal infection is hidden, and it is difficult to deliver prompt diagnosis. Candida, Aspergillus, Cryptococcus and Pneumocystis infection are common fungal infections in solid organ transplantation. High-risk factors of fungal infection after solid organ transplantation should be identified and prevented in advance, and prompt diagnosis and treatment should be carried out by combining the results of (1, 3)-β-D-glucan assay (fungal G-test), imaging examination and related body fluid culture. These interventions are of clinical significance to reduce the incidence of fungal infection and fatality after solid organ transplantation. In this article, common fungal infections after organ transplantation were reviewed, aiming to provide reference for the prevention and treatment of fungal infections after organ transplantation.

Research progress and application of donor-derived cell-free DNA in diagnosis and treatment of kidney transplantation

Yang Yang, Zhang Jian, Lin Jun

2022, 13(4): 455-462. doi: 10.3969/j.issn.1674-7445.2022.04.007

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Early diagnosis and treatment of rejection after kidney transplantation play a critical role in alleviating allograft injury. Detection of donor-derived cell-free DNA (dd-cfDNA) could be performed based on the next-generation sequencing and other techniques. The content of DNA fragments derived from necrotic and apoptotic donor kidney tissues in circulating body fluids could be determined by concentration and absolute quantitative methods, which has application potential in monitoring allograft injury in clinical practice. Compared with traditional serum creatinine and other indicators, dd-cfDNA detection may monitor allograft injury from several weeks to months in advance, providing a "time window" for clinical treatment and delaying graft failure. Along with deepening research of dd-cfDNA in recent years, dd-cfDNA has captivated widespread attention due to its non-invasiveness, high sensitivity and real-time evaluation of therapeutic effect. In this article, current study evidence and conclusions related to multidimensional application of dd-cfDNA detection in diagnosis and treatment of kidney transplantation were reviewed, and the future research and clinical application direction of dd-cfDNA were discussed, aiming to provide reference for widespread application of dd-cfDNA detection in clinical practice in China.

Research progress on kidney injury-related complications after heart transplantation

Xia Tian, Yu Wenjing, Li Fei

2022, 13(4): 463-468. doi: 10.3969/j.issn.1674-7445.2022.04.008

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In recent years, significant progress has been achieved in heart transplantation, perioperative management and application of immunosuppressants. Nevertheless, complications after heart transplantation are still main risk factors affecting the survival of recipients. Among them, acute kidney injury is a common complication during the early stage following heart transplantation. It may lead to secondary chronic kidney diseases after heart transplantation and progress into end-stage renal diseases, severely affecting the quality of life and long-term survival of recipients. Therefore, it is of significance to identify the risk factors of kidney injury after heart transplantation and deliver prompt interventions to improve clinical prognosis of heart transplant recipients. In this article, research progress on the incidence, risk factors, prevention and treatment strategies of kidney injury-related complications after heart transplantation was reviewed, aiming to provide reference for the prevention, diagnosis and treatment of kidney injury-related complications after heart transplantation and enhance clinical prognosis of recipients undergoing heart transplantation.

Diagnosis and treatment strategy of intestinal flora imbalance after liver transplantation

Bao Zhiye, Liu Hao

2022, 13(4): 469-474. doi: 10.3969/j.issn.1674-7445.2022.04.009

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Multiple short-term and long-term complications might occur after liver transplantation. In the early stage after liver transplantation, the incidence of multidrug-resistant bacteria is likely to cause different types of infection, one of which is intestinal flora imbalance. In the recent decade, a series of studies have demonstrated that intestinal flora plays an important role in maintaining intestinal homeostasis. Intestinal flora may interact with other organs via multiple patterns. Among which, gut-liver axis is one of the most critical channels for regulating microenvironment of the host. Changes in the quantity and composition of intestinal flora could lead to intestinal flora imbalance. In both local and systemic systems, extensive interaction exists between intestinal flora and immune system. In this article, the risk factors of intestinal flora imbalance after liver transplantation, influence of intestinal flora imbalance on liver transplant recipients and relevant treatment strategies were reviewed.

Protective role of expression of human complement regulatory protein hCD55 in islet xenotransplantation

Li Xin, Pan Dengke, Zhou Jia, Yan Jie, Chen Jun, Du Jiaxiang, Gong Manlin

2022, 13(4): 475-482. doi: 10.3969/j.issn.1674-7445.2022.04.010

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Objective To validate whether the expression of human cluster of differentiation 55 (hCD55) protein in porcine islet cells could inhibit the activation of complement components in human serum. Methods Four adult pigs with WT (wild type), GTKO [α-1, 3-galactosyltransferase (GGTA1) knockout], GTKO/hCD55 and hCD55 genotypes were selected. Islet cells were isolated from WT, GTKO and GTKO/hCD55 pigs, and the purity and insulin secretion function were detected. The expression of hCD55 at the DNA, RNA and protein levels was analyzed by agarose gel electrophoresis, reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry, respectively. Complement-dependent cytotoxicity assay and complement deposition assay were performed under the incubation conditions with fresh human serum. Results The purity of isolated porcine islet cells from three genotype pigs was > 75%, and the glycemic index was > 1. The expression of hCD55 messenger RNA(mRNA) and protein in GTKO/hCD55 porcine islet cells decreased the deposition of human complement component C3c and membrane-attacking complex C5b-9, and reduced the cytotoxicity. Conclusions The expression of hCD55 protein in porcine islet cells could inhibit the activation of human complement and reduce complement-mediated killing effect, indicating that hCD55 protein could exert complement protection effect on porcine islet cells. These findings provide theoretical basis for the application of hCD55 in islet xenotransplantation.

Study of end-to-end magnetic anastomosis technique of infrahepatic inferior vena cava in rats

Wang Xinying, Yang Lifei, Ren Lu, Wan Yong, Lyu Yi, Wang Shanpei, Lu Qiang

2022, 13(4): 483-488. doi: 10.3969/j.issn.1674-7445.2022.04.011

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Objective To develop a magnetic anastomosis device for infrahepatic inferior vena cava and verify its feasibility and safety in rat models. Methods According to the anatomical characteristics of rat inferior vena cava, a magnetic device suitable for end-to-end anastomosis of infrahepatic inferior vena cava was designed and manufactured. The device consisted of the inner and outer rings. The inner ring was a coated neodymium-iron-boron magnetic ring, and the outer ring was made of polyetheretherketone by 3D printing. Ten fine holes are evenly distributed on the outer ring, of which 5 fine holes were used to load the fine needles, and the other 5 fine holes were mutually connected with the fine needles of the contralateral anastomosis ring during anastomosis. The outer ring was uniformly loaded with fine needles and then bonded with the inner ring to form a magnetic anastomosis complex. Bilateral ends of vessels passed through the anastomosis ring and were fixed to the fine needles, and then end-to-end vascular anastomosis was performed by mutual attraction of two magnetic anastomosis rings. Twenty SD rats were selected and received end-to-end anastomosis of infrahepatic inferior vena cava with magnetic anastomosis device. The time of vascular occlusion, postoperative survival, postoperative anastomotic patency, gross observation and histological examination of anastomotic stoma were analyzed. Results All rats successfully completed end-to-end magnetic anastomosis of the infrahepatic inferior vena cava, and the time of vascular occlusion was 4~6 min. One rat died at 10 d after operation, and the other rats survived within postoperative 2 months. The patency rates of anastomotic stoma in surviving rats at postoperative 1 d, 3 d, 1 month and 2 months were 100%, 100%, 95% and 95%, respectively. At 2 months after operation, no obvious displacement and angulation of the anastomosis device were seen. No signs of corrosion and cracking of the anastomosis rings were observed. No evident hyperplasia and edema of surrounding tissues were noted. Bilateral ends of vessels were completely healed, and no obvious stenosis or thrombosis was found at the anastomotic stoma. Histological examination showed high continuity of bilateral vascular walls of anastomotic stoma, the inner surface of anastomotic stoma was covered by endothelial cells, and no thrombus or fibrous tissue was attached. Conclusions It is safe and feasible to utilize the self-designed magnetic anastomosis device to perform end-to-end magnetic anastomosis of infrahepatic inferior vena cava in rat models.

Predictive value of the initial MELD score and its derivative scores for early survival rate after liver transplantation in patients with liver failure

Lai Man, Wang Xin, Yao Qinwei, Liu Haixia, Xu Ying, He Li, Li Guangming

2022, 13(4): 489-494. doi: 10.3969/j.issn.1674-7445.2022.04.012

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Objective To explore the predictive values of the initial model for end-stage liver disease (MELD) score, MELD combined with serum sodium (MELD-Na) score and MELD combined with serum lactic acid (MELD-Lac) score for early survival rate after liver transplantation in patients with liver failure. Methods Clinical data of 135 recipients undergoing liver transplantation for liver failure were retrospectively analyzed. All patients were divided into the early survival group (n=110) and early death group (n=25) according to the survival at postoperative 28 d. Clinical data were compared between two groups. The optimal cut-off values of MELD, MELD-Na and MELD-Lac scores for predicting early survival rate after liver transplantation in patients with liver failure were determined by the receiver operating characteristic (ROC) curve. The predictive values of different scores for early survival rate after liver transplantation in patients with liver failure were evaluated. Results Significant differences were observed in the initial MELD, MELD-Na and MELD-Lac scores after liver transplantation between two groups (all P < 0.05). For the initial MELD, MELD-Na and MELD-Lac scores in predicting early survival rate after liver transplantation in patients with liver failure, the AUC were 0.653 [95% confidence interval (CI) 0.515-0.792], 0.648 (95%CI 0.514-0.781) and 0.809 (95%CI 0.718-0.900), the optimal cut-off values were 18.09, 18.09 and 19.97, Youden's indexes were 0.398, 0.380 and 0.525, the sensitivity was 0.680, 0.680 and 0.840, and the specificity was 0.720, 0.700 and 0.690, respectively. The AUC of MELD-Lac score was higher than those of MELD and MELD-Na scores, and the differences were statistically significant (both P < 0.05). Conclusions Compared with the initial MELD and MELD-Na scores after liver transplantation, the initial MELD-Lac score is a more reliable index for predicting early survival rate after liver transplantation in patients with liver failure.

Efficacy and safety of basiliximab and antithymocyte globulin in immune induction in kidney transplantation: a Meta-analysis

He Yue, Zheng Jin, Li Yang, Tian Xiaohui, Tian Puxun, Ding Xiaoming, Xue Wujun, Kang Yongming, Feng Yougang

2022, 13(4): 495-502. doi: 10.3969/j.issn.1674-7445.2022.04.013

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Objective To evaluate the efficacy and safety of basiliximab (BAS) and antithymocyte globulin (ATG) in immune induction therapy in kidney transplantation by systematic review and Meta-analysis. Methods Prospective randomized controlled clinical trials screening and comparing BAS and ATG in immune induction therapy in kidney transplantation were systematically searched from global databases, screened and compared. The quality of clinical trials was evaluated by Jadad scoring system and data extraction was performed. The effects of BAS and ATG on the incidence of acute rejection, survival rate of kidney allografts, survival rate of recipients, incidence of delayed graft function, infection, cytomegalovirus infection, malignant tumor, leukopenia and thrombocytopenia at 1 year after kidney transplantation were analyzed. Results A total of 10 clinical trials in English consisting of 1 721 kidney transplant recipients were searched, including 883 cases in the ATG group and 838 cases in the BAS group. No significant differences were observed in the incidence of acute rejection, survival rate of kidney allografts, survival rate of recipients, incidence of delayed graft function, infection, cytomegalovirus infection and thrombocytopenia at postoperative 1 year between the ATG and BAS groups (all P > 0.05). The incidence of malignant tumor and leukopenia at postoperative 1 year in the ATG group were significantly higher than those in the BAS group (both P < 0.05). Conclusions The use of ATG and BAS for immune induction therapy in kidney transplantation yield equivalent efficacy at postoperative 1 year, but BAS is safer than ATG. Clinical trials related to stratified analyses of immune risk are urgently required to achieve individualized precision treatment.

Predictive value of nomogram model based on PNI, SII and CAR for abdominal infection after liver transplantation

Luo Wenting, Cao Li, Lyu Dezhen, Liu Guoyin

2022, 13(4): 503-508. doi: 10.3969/j.issn.1674-7445.2022.04.014

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Objective To investigate the risk factors of abdominal infection after orthotopic liver transplantation. Methods Clinical data of 284 recipients undergoing orthotopic liver transplantation were retrospectively analyzed. All recipients were divided into the infection group (n=51) and non-infection group (n=233) according to the incidence of postoperative abdominal infection. Univariate and multivariate logistic regression analyses were used to identify the risk factors of abdominal infection. Nomogram prediction models were constructed and the prediction efficiency of these models was evaluated. The predictive value of continuous variables for abdominal infection was assessed. Results Among 284 recipients, 51 developed abdominal infection with an incidence of 18.0%. Diabetes mellitus before surgery[odds ratio (OR) 2.66, 95% confidence interval (CI) 1.13-6.14, P=0.013], long operation time (OR 1.98, 95%CI 1.03-3.57, P=0.038), low prognostic nutritional index (PNI) (OR 2.18, 95%CI 1.06-4.44, P=0.023), high systemic immune-inflammation index (SII) (OR 2.21, 95%CI 1.06-4.78, P=0.012) and high C-reactive protein/albumin ratio (CAR) (OR 1.90, 95%CI 1.05-3.49, P=0.029) were independent risk factors for abdominal infection after liver transplantation. The area under curve (AUC) of nomogram model for predicting abdominal infection after liver transplantation was 0.761. The standard model yielded high consistency. CAR, PNI and SII were all predictors of abdominal infection after liver transplantation (all P < 0.05), with AUC of 0.648, 0.611 and 0.648, and cut-off values of 2.75, 43.15 and 564.50, respectively. Conclusions CAR, SII and PNI are predictors of abdominal infection after liver transplantation. The nomogram model based on PNI, SII and CAR may effectively predict the incidence of abdominal infection after liver transplantation.

Changes and significance of lymphocyte subsets in recipients with acute rejection after liver transplantation

Wang Ruolin, Li Han, Jia Ya'nan, Xu Wenli, Li Xianliang, He Qiang, Zhu Jiqiao

2022, 13(4): 509-515. doi: 10.3969/j.issn.1674-7445.2022.04.015

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Objective To evaluate the changes and significance of lymphocyte subsets in the recipients with acute rejection after liver transplantation. Methods The recipients presenting with acute rejection after liver transplantation were assigned into the rejection group (n=17), and their counterparts with stable liver function were allocated into the control group (n=17) according to the ratio of 1∶1 by propensity score matching method. The incidence of acute rejection after liver transplantation was analyzed, and the concentration of tacrolimus in the recipients was compared between two groups. The absolute value and proportion of lymphocyte subsets in peripheral blood were compared between two groups. The diagnostic value of lymphocyte subsets for acute rejection after liver transplantation was assessed by the receiver operating characteristic (ROC) curve. The absolute value and proportion of lymphocyte subsets in the rejection group were compared before and after treatment. Results Among 17 recipients in the rejection group, 4 cases developed acute rejection within postoperative 28 d, and 13 cases had acute rejection within postoperative 29-180 d. No significant difference was noted in the tacrolimus concentration between two groups (P=0.295). Compared with the control group, the proportions of peripheral blood T cells, CD4⁺T cells, B cells and natural killer (NK) T cells were significantly increased in the rejection group (all P < 0.05). The elevated proportion of NKT cells in the early stage after liver transplantation was an independent risk factor for acute rejection following liver transplantation[odds ratio (OR) 1.774, 95% confidence interval (CI) 1.059-2.971, P=0.029]. ROC curve analysis showed that the area under curve (AUC) of CD4⁺T cells, B cells and NKT cells was 0.76, 0.73 and 0.77, respectively. The AUC of combined use of CD4⁺T cells, B cells and NKT cells was 0.89, with a cut-off value of 0.69, sensitivity of 0.706 and specificity of 0.941. After corresponding treatment, all recipients were gradually recovered, and liver functions were eventually restored to normal in the rejection group. After treatment, the proportion of T cells, CD4⁺T cells, CD8⁺T cells and NK cells was significantly decreased (all P < 0.05). Conclusions The elevated proportion of NKT cells indicates an increased risk of acute rejection after liver transplantation. Combined use of CD4⁺T cells, B cells and NKT cells may deliver early detection and diagnosis of acute rejection after liver transplantation.

Protein A immunoadsorption in the treatment of de novo DSA-mediated acute rejection after lung transplantation

Xu Yu, Lian Qiaoyan, Chen Ao, Wang Xiaohua, Xu Xin, He Jianxing, Ju Chunrong

2022, 13(4): 516-521. doi: 10.3969/j.issn.1674-7445.2022.04.016

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Objective To investigate the treatment on de novo donor specific antibody (dnDSA) mediated acute rejection after lung transplantation. Methods Clinical data of 1 recipient with antibody-mediated rejection (AMR) early after lung transplantation was retrospectively analyzed. The process of diagnosis and treatment were assessed. Results The recipient underwent right lung transplantation due to systemic sclerosis-associated end-stage interstitial lung disease. Preoperatively, classⅠ panel reactive antibody (PRA) was positive (11%). No pretreatment was given before transplantation. Antithymocyte globulin induction therapy was delivered on the day of transplantation and postoperatively. The recipient was properly recovered early after transplantation. Chest tightness and shortness of breath occurred at postoperative 13 d, which were progressively worsened and rapidly progressed into type Ⅰ respiratory failure. Class Ⅰ PRA was increased to 58%, and dnDSA was observed at the loci of A24: 02. The mean fluorescence intensity (MFI) was 2 110. According to the guidelines of International Society for Heart and Lung Transplantation, the recipient was diagnosed as possible AMR. After comprehensive treatment including plasmapheresis, protein A immunoadsorption, glucocorticoid pulse, rituximab and immunoglobulin intravenous drip, the PRA and DSA levels were gradually decreased, and the MFI of DSA was 0 at postoperative 20 d. Clinical condition of the recipient was gradually improved. The dyspnea was healed, shortness of breath was eased, respiratory failure was treated, and pulmonary effusion was gradually absorbed. At postoperative 45 d, the recipient was discharged after full recovery. During 1-year follow-up, the recipient was physically stable and obtained normal quality of life. Class Ⅰ PRA was 5%, and class Ⅱ PRA was negative. No DSA was noted. Conclusions Based on traditional drug therapy, supplement of protein A immunoadsorption therapy may effectively eliminate DSA from the circulating blood of the recipient and mitigate the damage of target organs. Ideal short- and long-term prognosis may be achieved. Traditional drug therapy combined with immunoadsorption may yield ideal efficacy in treating AMR after lung transplantation.

Major molecular events of reactivation of human cytomegalovirus after allogeneic hematopoietic stem cell transplantation

Wei Aiping, Song Yaqin, Zhou Xiuying, Peng Wei, Xie Zhengjun

2022, 13(4): 522-529. doi: 10.3969/j.issn.1674-7445.2022.04.017

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Immune deficiency of the host caused by allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the initial factor of reactivation of latent human cytomegalovirus (HCMV). The risk factors of reactivation of HCMV in allo-HSCT recipients consist of the serological status of HCMV in donors and recipients, the matching degree of human leukocyte antigen (HLA) and pretreatment patterns, etc. The reactivation of HCMV is associated with the expression of a series of viral cleavage and proliferation proteins induced by the overexpression of major immediate early promoter/enhancer (MIEP) in the viral genome. In this article, the risk factors of reactivation of HCMV after allo-HSCT, the molecular changes related to maintaining latent infection of HCMV, the key role of MIEP overexpression in reactivation of HCMV, and the molecular pathways involved in reactivation of HCMV after allo-HSCT were reviewed and the major molecular events of reactivation of HCMV after allo-HSCT were elucidated, aiming to provide reference for the prevention and treatment of cytomegaloviral disease (CMVD) after allo-HSCT.

Research progress on the role of exosome in rejection after lung transplantation

Jiang Guanyu, Chen Siyuan, Xu Yongrui, Zheng Mingfeng, Mao Wenjun

2022, 13(4): 530-536. doi: 10.3969/j.issn.1674-7445.2022.04.018

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Rejection after lung transplantation, including acute rejection (AR) and chronic rejection manifested with chronic lung allograft dysfunction (CLAD), is the main factor affecting the long-term survival of allografts. Exosome, a type of extracellular nanovesicle for intercellular communication among eukaryotic cells, could carry complex biological information and participate in various physiological and pathological processes. Exosome has become a critical immune medium in rejection, regulates the incidence and development of rejection through multiple pathways, and also plays a key role in the monitoring and management of rejection. In this article, the type of rejection after lung transplantation, the mechanism underlying the role of exosome in regulating rejection, exosome acting as biomarkers and the application in rejection treatment were reviewed, aiming to provide a novel direction for comprehensive diagnosis and treatment of rejection following lung transplantation.

Research progress on the role of bile salts in ischemic-type biliary lesion after liver transplantation

Liu Hanlin, Dai Xin, Xiao Yijun, Wu Wei

2022, 13(4): 537-542. doi: 10.3969/j.issn.1674-7445.2022.04.019

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Ischemic-type biliary lesion (ITBL) refers to biliary tract injury caused by insufficient blood supply of hepatic artery, which is one of the main factors affecting the long-term survival and quality of life of liver transplant recipients. The incidence of ITBL is associated with cold and warm ischemia, acute and chronic rejection, cytomegalovirus infection and the bile effect, etc. The occurrence of ITBL is a complicated process involving with multiple factors and steps. The therapeutic option of ITBL is extremely limited. A large proportion of ITBL patients should undergo repeated liver transplantation. ITBL has become one of the most critical factors preventing further advancement of liver transplantation. Hence, it is of significance to strengthen prevention and explore more effective modalities. Recent studies have found that toxic injury of bile salts plays a central role in ITBL. Active regulation of bile components, regulation of bile acid-related receptor expression and blockage or activation of bile acid-related signaling pathways probably have potentials in the prevention and treatment of ITBL. In this article, the cytotoxicity of bile salts and the mechanism of bicarbonate umbrella in the incidence and progression of ITBL after liver transplantation were reviewed, aiming to provide reference for the diagnosis and treatment of ITBL.

2022 Vol. 13, No. 4