ABSTRACT
Pancreas transplantation and pancreas-kidney transplantation are the optimal treatment for renal failure caused by type 1 diabetes mellitus, partial type 2 diabetes mellitus and their complications. Pancreas transplantation mainly includes simultaneous pancreas-kidney transplantation (SPK), pancreas transplantation after kidney transplantation (PAK) and pancreas transplantation alone (PTA). Among all types of pancreas transplantation, biopsy of pancreas allograft remains the best method for definitively diagnosing rejection and differentiate it from other complications. In this article, biopsy methods of pancreas allograft and related research progress, diagnostic criteria and research progress on rejection of pancreas allograft biopsy, and main complications and pathological manifestations of pancreas allograft were illustrated, aiming to provide reference for guiding the clinical diagnosis of the above mentioned complications and ensuring the long-term survival of pancreas allografts and recipients.
ABSTRACT
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.
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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.
ABSTRACT
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.
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Antibody-mediated rejection (AMR), also known as humoral rejection, is an immune injury caused by rejection involved with multiple humoral immune effectors, such as antibodies and complements, etc. AMR plays a pivotal role in hyperacute, acute and chronic rejection. In this article, the basic definition of AMR, the research progress and major achievements on AMR pathology according to Banff classification on allograft pathology (Banff classification), and main pathological characteristics of AMR in renal allograft were reviewed, aiming to provide reference for accurate diagnosis and timely treatment of AMR, and guarantee the long-term survival of renal graft and recipients.
ABSTRACT
Regulatory T cell (Treg) is a subset of T cells that negatively regulates immunity and has the function of inhibiting rejection. The specific modification of Treg by chimeric antigen receptor (CAR) technology can successfully chime donor-specific antigen onto the surface of Treg, thus regulating the immune function of the body in a real-time manner. It provides a novel and promising therapeutic option for inducing immune tolerance. In this article, research progresses on Treg in immune related diseases, main difficulties in the realization of CAR-Treg technology and its role in inducing transplantation immune tolerance were reviewed, and the opportunities and challenges of CAR-Treg application in the field of organ transplantation are prospected.
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In this paper, forefront hotspots in clinical and applied basis of organ transplantation as well as translational medicine during 2019 American Transplant Congress (ATC) were summarized. It involved transplantation clinical priorities and difficulties which were concerned by transplant surgeons. These hot topics included the immunological mechanisms, risk factors, prognosis evaluation and important biological markers of donor specific antibody (DSA) and antibody-mediated rejection (AMR), desensitization strategy in highly sensitized patients and progress of AMR prevention and treatment, current status and development direction of clinical immune tolerance, hotspots and prevention progress on transplantation-related infection, and brief evaluation of various donor organ mechanical perfusion methods, etc.
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Objective To investigate the effect of double filtration plasmapheresis (DFPP) upon the removal of donor specific antibody (DSA) in highly sensitized recipients with renal transplantation. Methods Four highly sensitized recipients undergoing renal transplantation received 7 cycles of DFPP. Luminex technology was adopted to monitor the changes of DSA. Clinical efficacy, incidence of acute rejection and adverse reactions were observed. Results After DFPP, the DSA MFI [1036 (0-4113)] was significantly declined than that before treatment [6446 (2999-12905), Z= -2.503, P=0.012]. No hyperacute rejections occurred in four highly sensitized recipients undergoing renal transplantation.Acute rejection was noted in one case, which was mitigated by postoperative DFPP and adjustment of immunosuppressive agents. During postoperative follow-up, the function of transplant kidney was normal and no rejection reactions occurred. The level of albumin was decreased after DFPP. Conclusions DFPP can effectively remove the DSA in the recipients.It is an efficacious and safe approach to prevent the incidence of acute rejections in highly sensitized recipients after renal transplantation.
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Objective To summarize the clinical experience of the application of bortezomib desensitization regime prior to secondary renal transplantation in a highly-sensitized recipient. Methods At 13, 10 and 6 d prior to secondary renal transplantation, one patient positive for donor specific antibody (DSA) was subcutaneously administered with bortezomib at a dose of 1.3 mg/m2 combined with a low dose of immunoglobulin. Postoperatively, immunosuppressive regime of tacrolimus (FK506), mycophenolat sodium and methylprednisolone was adopted. The serum creatinine (Scr), blood urea nitrogen (BUN) levels, FK506 concentration, DSA titre, C3d binding DSA (C3d-DSA) titre, pathological biopsy of the renal graft and adverse reactions were observed. Results During 12-month follow-up after administration of bortezomib, the Scr level was declined and maintained at 130 μmol/L, and the BUN level was remained at 3.9 mmol/L. The DSA level was significantly decreased and the C3d-DSA was negative. At postoperative 4 and 9 months, pathological biopsy of the renal graft revealed that the patient was positive for C4d, prompting the chronic active antibody mediated rejection (AMR). The patient presented with grade Ⅲ peripheral neuropathy. Conclusions Application of preoperative bortezomib desensitization regime can effectively down-regulate the DSA level in the recipient and avert the incidence of acute rejection in highly-sensitized patients undergoing secondary renal transplantation. Comprehensive treatment using bortezomib is recommended for preoperative desensitization in the highly-sensitized transplant recipients.
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Objective To compare the change features of anti-donor specific antibody (DSA) in different species of sentitized mice after skin transplantation. Methods All mice were divided into the Balb/c → C57BL/6 (6 pairs) and Balb/c → C3H skin transplantation groups (6 pairs). At d0, d2, d4, d7, d13, d17, d28, d35, d42, d49 and d56 after skin transplantation, the serum sample was prepared for detection of DSA-IgG and DSA-IgM levels. Results Moderate increase was noted in the DSA-IgG level in the sensitized mice within 1 week after skin transplantation. The IgG level was significantly increased within 1-4 week and peaked and stabilized within 4-8 week. No significant variation was observed in the DSA-IgM level at 8 weeks after skin transplantation. In the Balb/c → C57BL/6 skin transplantation group, the DSAIgG level was significantly lower than that in the Balb/c → C3H group. Statistical significance was identified in the IgG levels between two groups at d2, d17, d28, d35, d42, d49 and d56 after skin transplantation (all P<0.05). No statistical significance was noted in the DSA-IgM levels between two groups at each time point (all P>0.05). Conclusions Advancing the time of renal transplantation after skin transplantation moderately in the Balb/c → C3H group, or changing to the lower immunoreactive combination of Balb/c → C57BL/6 are aimed to establish AMR mouse models with mild rejection reaction.