涤纶毡片人工韧带的实验研究

目的：观察涤纶毡片植入肌肉、脂肪、皮下组织且的组织相容性差异。方法：用涤纶毡片植入60只白鼠不同部位，用组织学、电镜和ECT方法观察其与组织的反应。结果：涤纶毡片与肌肉组织相容性最好，脂肪组织次之，皮下组织对涤纶毡片有轻度排异反应。结论：涤纶毡片在不同组织存在组织相容性差异；能用于修复和重建人体受损的韧带组织。     

Development of clinical immunosuppression for organ transplantation

The progress in the understanding of allograft rejection since the first modern kidney transplantation is enormous. The concept of the histocompatibility complex (HLA system) was born and the loci for the related genes are now identified. The actual structure of HLA antigens and the molecules (lymphokines) released by them are being understood. A population of lymphocytes (suppressor cells) which reduces the host immune response to tissue allografts has also been identified. With advanced understanding, ideas and methods for immunosuppression have been developed. Hyperacute rejection due to presensitization (secondary to preformed HLA antibody) ought to be avoided or attenuated, if it were to happen. The significance of previous blood transfusion or multiple pregnancies were clarified in this regard. The tests to determine such immunological reactivity were devised. Steroids, azathioprine and cyclosporine which are presently in use for immunosuppression were reviewed as to their actions, effects and side-effects. Total lymphoid irradiation presently appears as a potential effective immunosuppressive procedure and is currently being tried in certain transplant centers. The superiority of monoclonal antibodies against polyclonal antilymphocyte antibodies has been confirmed, although the latter also has various useful actions. Finally, the need and possible means to facilitate donor specific unresponsiveness are mentioned in perspectives for the future management of clinical organ transplantation.     

Historical Matching Strategies in Kidney Paired Donation: The 7‐Year Evolution of a Web‐Based Virtual Matching System

Failure to convert computer‐identified possible kidney paired donation (KPD) exchanges into transplants has prohibited KPD from reaching its full potential. This study analyzes the progress of exchanges in moving from “offers” to completed transplants. Offers were divided into individual segments called 1‐way transplants in order to calculate success rates. From 2007 to 2014, the Alliance for Paired Donation performed 243 transplants, 31 in collaboration with other KPD registries and 194 independently. Sixty‐one of 194 independent transplants (31.4%) occurred via cycles, while the remaining 133 (68.6%) resulted from nonsimultaneous extended altruistic donor (NEAD) chains. Thirteen of 35 (37.1%) NEAD chains with at least three NEAD segments accounted for 68% of chain transplants (8.6 tx/chain). The “offer” and 1‐way success rates were 21.9 and 15.5%, respectively. Three reasons for failure were found that could be prospectively prevented by changes in protocol or software: positive laboratory crossmatch (28%), transplant center declined donor (17%) and pair transplanted outside APD (14%). Performing a root cause analysis on failures in moving from offer to transplant has allowed the APD to improve protocols and software. These changes have improved the success rate and the number of transplants performed per year.     

小鼠主要组织相容性复合物基因各位点的提取和质粒的构建

目的 提取小鼠的主要组织相容性复合物(MHC)基因各个位点,构建质粒,以用于转基因实验.方法 提取小鼠RNA,逆转录cDNA,以嵌套聚合酶链反应(PCR)的方法扩增,将产物与T载体连接、克隆和测序;用内切酶切下,再与表达型载体连接,再次测序挑选克隆.结果 嵌套PCR后,产物通过测序证实为目的 基因序列,与T载体、表达型载体的连接和克隆后,经测序证实并挑选得到了正确的克隆.结论 MHC各位点基因可以通过嵌套PCR扩增获得;构建的表达型载体质粒可用于今后转入受者的实验.     

Detrimental role of donor-recipient HLA-DQ5 and -DQ6 disparities on cadaver kidney graft survival

Donor-recipient incompatibility (D + R ?) for HLA-DQ₁, but not for -DQ₂ or -DQ₃, is associated with an adverse effect on cadaver kidney graft survival. Until now, however, DQ₁ recipients of DQ₁-negative kidneys (D ? R +) have not been differentiated from DQ₁-identical donor-recipient pairs (D + R +) and splits of DQ₁, DQ₅ and DQ₆, have not been studied in that respect. From our data (480 transplantations performed from January 1980 to December 1990), three donor-recipient DQ combinations (D + R +, D ? R +, D + R ?) were formed for each of four DQ specificities (DQ₂, DQ₃, DQ₅, DQ₆). As DR?DQ linkage disequilibrium is well conserved in caucasoid individuals, DQ specificities were inferred from the associated DR specificities. Graft survival rate (%) was significantly lower for the DQ₅ D + R ? and the DQ₆ D ? R + combinations when compared with the other corresponding DQ combinations, whereas no significant difference was observed between the DQ₂ and DQ₃ combinations. In conclusion, if DQ₁ plays a prominent role in kidney graft survival, the effects of its splits appear dissociated: DQ₅ could be a marker of high antigenicity and DQ₆ a marker of high responsiveness.     

胎脑组织移植免疫排斥反应的实验研究

为了解脑组织移植是否存在排斥反应，将胎龄１６－１８天的同种及异种胎脑皮质组织移植到Ｗｉｓｔａｒ大鼠预制脑腔内。术后给予环孢素Ａ治疗。移植后动物在不同时间内分批处死，进行免疫组织化学染色，了解移植区局部Ｔ淋巴细胞亚群浸润情况及主要组织相容性复合物Ⅱ类抗原的表达情况。     

Assessing the utilization of high‐resolution 2‐field HLA typing in solid organ transplantation

HLA typing in solid organ transplantation (SOT) is necessary for determining HLA‐matching status between donor‐recipient pairs and assessing patients’ anti‐HLA antibody profiles. Histocompatibility has traditionally been evaluated based on serologically defined HLA antigens. The evolution of HLA typing and antibody identification technologies, however, has revealed many limitations with using serologic equivalents for assessing compatibility in SOT. The significant improvements to HLA typing introduced by next‐generation sequencing (NGS) require an assessment of the impact of this technology on SOT. We have assessed the role of high‐resolution 2‐field HLA typing (HR‐2F) in SOT by retrospectively evaluating NGS‐typed pre‐ and post‐SOT cases. HR‐2F typing was highly instructive or necessary in 41% (156/385) of the cases. Several pre‐ and posttransplant scenarios were identified as being better served by HR‐2F typing. Five different categories are presented with specific case examples. The experience of another center (Temple University Hospital) is also included, whereby 21% of the cases required HR‐2F typing by Sanger sequencing, as supported by other legacy methods, to properly address posttransplant anti‐HLA antibody issues.     

A serologic approach to the definition of human prostatic carcinoma antigens

We have used an immunoaffinity system whereby immunoglobulin from patients with prostatic carcinoma was coupled to solid phase protein A; the immobilized IgG was subsequently exposed to radiolabeled antigen from autochthonous or allogeneic primary tumor extracts or to radiolabeled antigen from a nude mouse-supported prostatic carcinoma cell line. Material specifically bound by prostatic carcinoma patient immune IgG was quantitatively eluted from the immunoadsorbent and characterized with regard to molecular weight. Sequential adsorption analyses of patient sera with normal human tissue pools, normal prostatic tissue, prostatic carcinoma tissue, and tissue from other urogenital malignancies has allowed a definition of those antigenic specificities relevant in the immunobiology of prostatic carcinoma. The patient humoral response was observed to be directed primarily toward a complex array of antigens representing normal human tissue components; serorecognition of prostate tumor associated antigens was discernible from that of common tissue antigens only after rigorous adsorption analyses. Preliminary results indicate that the prostatic cancer patient humoral antibody response may be directed toward either altered histocompatibility complex antigens or toward antigens physically associated with histocompatibility complex antigens.     

Major histocompatibility complex class II antigens in steroid-sensitive nephrotic syndrome in Chinese children

Steroid-sensitive nephrotic syndrome (SSNS) has been postulated to have an immunopathogenic basis. To determine whether SSNS is associated with specific class II antigens of the major histocompatibility complex, we studied HLA-DR and DQ in 40 children with SSNS. HLA-DR7 was found in 40% of SSNS patients compared with only 11.23% of controls (P=0.00025). HLA-DR9 occurred in 71.40% of patients with frequent relapses, compared with 27.37% of controls (P=0.016). It seems likely that SSNS has an immunogenetic basis.     

大鼠抗小鼠组织相容性抗原抗体的制备与纯化

为进一步了解异种移植间免疫排斥反应的抗体特性，采用NIH小鼠牌细胞免疫SD大鼠，制备大鼠抗小鼠组织相容性抗原抗血清，经辛酸沉淀、羟基磷灰石层析技术纯化抗体。结果：制备的大鼠抗小鼠组织相容性抗原抗血清具有较高效价（＞1：640），辛酸、羟基磷灰石二步法纯化的抗体具有纯度好、收获率高、能保留免疫原性、条件温和等特点。表明此法是制备各种抗组织相容性抗原抗体的有效方法。     

The Influence of Donor and Recipient Gender Incompatibility on Corneal Transplant Rejection and Failure

In vascularized organ transplants, gender mismatches have higher rates of immunological rejection. We investigated the influence of gender incompatibility, including H‐Y incompatibility, on corneal transplant graft rejection and failure. Patients were included who had undergone a first corneal transplant for keratoconus (KC), Fuchs endothelial dystrophy (FED), pseudophakic bullous keratopathy (PBK), infection and other indications. A Cox regression model was fitted for each indication to determine factors affecting graft failure and rejection at 5 years. The impact of gender, including H‐Y, matching was analyzed after accounting for other factors, including known risk factors. Of 18 171 patients, 4314 had undergone a transplant for FED, 4783 for KC, 3669 for PBK, 1903 for infection and 3502 for other disorders. H‐Y mismatched (male [M]→female [F]) corneas were at greater risk of graft failure or rejection. For FED, F→F were 40% less likely to fail (p < 0.0001) and 30% less likely to reject (p = 0.01); M→M were 20% less likely to fail (p = 0.04) and 30% less likely to reject (p = 0.01). For KC, M→M matched corneas were 30% less likely to fail (p = 0.05) and 20% less likely to reject (p = 0.01) compared with H‐Y mismatches. H‐Y antigen mismatched (M→F) patients were at greater risk of rejection or graft failure.     

Mixed leukocyte culture in uraemia

Summary The activities of mixed leucocyte cultures (MLC) prepared from pairs of healthy subjects were estimated from the uptake of tritiated thymidine by the cultures. It was confirmed that MLC is a practical method for detecting identical twins amongst siblings. MLC has not often been employed for donor selection for renal transplantation, mainly because of the impaired MLC reactivity of leukocytes from uraemic patients. An attempt was made to separate lymphocytes from uraemic leukocyte-rich plasma, which always has a high proportion of neutrophils. A lymphocyterich fraction of uraemic leukocytes has MLC reactivity comparable to that of non-uraemic leukocytes.     

Human Renal Allograft Rejection Despite the Absence of Allogeneic Passenger Leukocytes

Passenger leukocytes have been suggested to be both pro-tolerant and immunogenic. The opportunity to evaluate the role of allogeneic passenger leukocytes in humans was presented by a 47-year-old man who donated bone marrow to his HLA-identical leukemic sister. Eleven years later he developed renal failure. The sister's marrow was noted to be 100% XY karyotype and free of malignancy. She donated a kidney to her brother. Immunosuppression was tapered following transplantation. After 6 months, the recipient was on monotherapy sirolimus, 1 mg every third day. A surveillance biopsy was normal and sirolimus was stopped. Eight weeks later, he presented with severe rejection that reversed with Thymoglobulin. Renal function returned to baseline and has been stable on conventional immunosuppression.     

Blastocyst MHC 基因转染延长小鼠移植心脏存活时间

目的 探讨Blastocyst MHC基因经供心冠状动脉转染对移植心脏存活时间的影响. 方法 分别以近交系健康雄性Balb/c小鼠和C57BL/6小鼠为供、受者,制备小鼠颈部心脏移植模型,对照组供心以0～4℃托马斯Ⅱ溶液灌注;环孢素A(CsA)组供心用前述方法灌注,术后受者腹腔注射CsA 5 mg·g1·d-1;转染组供心以含Blastocyst MHC基因转染质粒的托马斯Ⅱ溶液灌注;联合处理组供心以含Blastocyst MHC基因转染质粒的托马斯Ⅱ溶液灌注,术后腹腔内注射CsA.观察各组移植心脏存活时间和组织学变化,测定移植心脏组织中Blastocyst MHC基因mRNA表达以及外周血CD4+ CD25+调节性T淋巴细胞(Treg细胞)及CD3+ CD8+ T淋巴细胞的变化. 结果 CsA组、转染组和联合处理组移植心脏存活时间较对照组明显延长(P＜0.115),其中以联合处理组最为显著,达(20.50±5.61)d.转染组术后1、3 d的Blastocyst MHC基因mRNA表达水平较对照组明显升高(P＜0.05).术后7 d,联合处理组的排斥反应程度最轻,其冠状动脉内膜增生也最轻.术后7 d,CsA组和联合处理组Treg细胞明显多于对照组(P＜0.05),而CD3+ CD8+ T淋巴细胞明显少于对照组(P＜0.05). 结论 移植前转染Blastocyst MHC基因能够通过上调Treg细胞、抑制CD3+ CD8+ T淋巴细胞而延长小鼠移植心脏存活时间,与CsA联合有协同作用.     

Major histocompatibility complex antigens in steroid-responsive nephrotic syndrome

An increased frequency of specific major histocompatibility complex (MHC) class I, II and III antigens in children with steroid-responsive nephrotic syndrome (SRNS) has been reported. This frequency distortion, in some cases, is thought to affect the outcome of the disorder. We studied the phenotypic frequency of HLA antigens-A,-B, and-DR, as well as complement proteins Bf and C4 in an unrelated population of 25 SRNS children. Complete MHC haplotypes were also derived for four families in which 8 individuals developed SRNS. HLA-DR8, with a relative risk of 4.8, showed the strongest association with SRNS. Nonetheless, the 95% confidence intervals of this and the relative risks for all other antigens fell below 1.0. No common haplotype was found in SRNS patients in whom complete family studies were available, and disease and inheritance of the MHC were discordant in two of these families. In this study of well-characterized SRNS patients we were unable to discover a clear association between this disorder and the MHC.     

The Road to HLA Antibody Evaluation: Do Not Rely on MFI

Technological advances in HLA laboratory testing undoubtedly improved the sensitivity and specificity of HLA antibody assessment but not without introducing a set of challenges regarding data interpretation. In particular, the introduction of solid‐phase single‐antigen bead (SAB) antibody assessment brought the belief that mean fluorescence intensity (MFI) was a quantifiable value. As such, MFI levels heavily influenced HLA antibody reporting, monitoring, and clinical practice. However, given that SAB testing was neither intended for nor approved to be quantifiable, is the use of MFI in current clinical and laboratory practice valid? What, if anything, does this numerical value actually reveal about the pathogenic potential of the antibody? What are the pitfalls and caveats associated with reporting MFI? Herein, we travel the road to HLA antibody assessment and explore the reliability of MFI values to make clinical decisions.     

Association of malignant glioma with the human leukocyte antigen,HLA-A24(9)

Many immune responses are controlled by genes of the major histocompatibility complex (MHC). In humans these include the loci encoding the HLA-A,-B,-C,-DR,-DQ and-DP antigens, and many diseases have been linked with these. However, little information is available about any connection between malignant tumors and HLA. In this study the possible association of HLA-A,-B,-C and-DR specificities with susceptibilitities to malignant glioma was investigated in 42 patients with malignant glioma and 42 controls with non-glial intracranial tumors using the Terasaki-NIH standard method. The data were also compared with those of the 11th International HLA Workshop. The result showed that a high frequency of HLA-24(9) was observed in patients with intracranial malignant gliomas, which was not common in other, non-glial patient groups. In animals the MHC acts in defense against virally induced tumors, but until now there has been no evidence that they do so in human gliomas. Our discovery of its association with an HLA antigen is important for understanding the immunogenetic basis of susceptibility to glioma.     

Alloantibody Responses After Renal Transplant Failure Can Be Better Predicted by Donor–Recipient HLA Amino Acid Sequence and Physicochemical Disparities Than Conventional HLA Matching

We have assessed whether HLA immunogenicity as defined by differences in donor–recipient HLA amino‐acid sequence (amino‐acid mismatch score, AMS; and eplet mismatch score, EpMS) and physicochemical properties (electrostatic mismatch score, EMS) enables prediction of allosensitization to HLA, and also prediction of the risk of an individual donor–recipient HLA mismatch to induce donor‐specific antibody (DSA). HLA antibody screening was undertaken using single‐antigen beads in 131 kidney transplant recipients returning to the transplant waiting list following first graft failure. The effect of AMS, EpMS, and EMS on the development of allosensitization (calculated reaction frequency [cRF]) and DSA was determined. Multivariate analyses, adjusting for time on the waiting list, maintenance on immunosuppression after transplant failure, and graft nephrectomy, showed that AMS (odds ratio [OR]: 1.44 per 10 units, 95% CI: 1.02–2.10, p = 0.04) and EMS (OR: 1.27 per 10 units, 95% CI: 1.02–1.62, p = 0.04) were independently associated with the risk of developing sensitization to HLA (cRF > 15%). AMS, EpMS, and EMS were independently associated with the development of HLA‐DR and HLA‐DQ DSA, but only EMS correlated with the risk of HLA‐A and ‐B DSA development. Differences in donor–recipient HLA amino‐acid sequence and physicochemical properties enable better assessment of the risk of HLA‐specific sensitization than conventional HLA matching.