摘要:

Using a panel of monoclonal antibodies, immunohistological analysis was performed on frozen sections taken from 14 peritransplant renal biopsies and 42 biopsies taken 6±2 days posttransplantation. The following parameters were examined: tubular expression of HLA-DR, DP, and DQ and infiltration with T lymphocytes and macrophages. Of the 42 posttransplant biopsies, 26 were diagnosed as rejecting and 16 as nonrejecting according to clinical and histopathological criteria. HLA-DR antigens were strongly expressed on 8 of 14 peritransplant biopsies, 23 of 26 rejecting biopsies and 13 of 16 nonrejecting biopsies. Tubular expression of HLA-DP and DQ was weak or absent.In the rejecting biopsies there was a significantly increased infiltrate of T lymphocytes of all phenotypes and of macrophages when compared with the nonrejecting biopsies. Graft outcome was invariably favorable in the nonrejecting group, with no graft losses in the first posttransplant year. There were 4 graft losses in the rejecting group, all due to rejection, and further analysis revealed that all 4 had macrophage-dominated infiltrates in their early allograft biopsies. We conclude that immunohistological analysis of early allograft biopsies provides an accurate prognosis of subsequent graft acceptance or rejection and that early macrophage infiltration is a poor prognostic sign.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The organ shortage remains a major barrier to renal transplantation in the United States today. The use of unconventional living donors, including genetically unrelated adults and related minors, could help increase the number of kidneys available for transplantation. Although these donor sources had generally been discarded, recent developments (including improved success and the demonstration of minimal risk) have caused some to reconsider this policy. Therefore, we surveyed all U.S. transplant centers regarding their attitudes toward unconventional living kidney donors. Of the nearly 60% responding: 76% would consider using spouses and 48% would even consider adult friends; 64% would consider using monozygotic twin minors and 43% would consider closely related non-twin minors; the mean minimum donor age accepted was 16±3 years, and the range was wide. On the other hand, many centers expressed reservations about these donor sources and indicated that such donors are seldom used. We conclude that under certain circumstances many U.S. transplant centers would consider accepting unconventional living kidney donors. Yet, at the same time, the centers appear uneasy about actually using these donors and no clear consensus exists. Our data indicate a need to openly readdress these issues.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Campath-1M is a rat monoclonal IgM antibody that binds human complement and recognizes virtually all peripheral human mononuclear cells. It is known to be effective in T cell depletion of bone marrow grafts, and encouraging results were obtained in a pilot study in which the antibody was used in prevention and treatment of rejection of kidney, pancreas, and liver allografts. In this randomized controlled clinical trial, Cam-path-1M has been evaluated as a prophylactic agent following renal allografting. It is shown that patients who received a 10-day course of the antibody immediately postoperatively, in addition to standard therapy with high-dose cyclosporine (17 mg/kg), experienced a significantly lower incidence of early acute cellular rejection than control patients who received cyclosporine alone. There was no evidence of “rebound” rejection following the end of antibody treatment to suggest that rejection had merely been delayed. However, patients who received this additional immunosuppression experienced a significantly higher incidence of serious infections than controls, this negating any benefit from the treatment in terms of graft survival. Thus, a monoclonal antibody of broad specificity directed against lymphocytes may be effective as a prophylactic agent after organ transplantation but its use should be accompanied by a reduction in other immunosuppressive drugs.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Antihuman lymphocyte rabbit (or horse) gamma globulins used in recipients of organ transplantation are prepared against thymocytes or immortalized cell lines, the only two sources so far allowing enough antigen preparation. These cells lack, however, the surface determinants characteristic of alloreactive blasts involved in the rejection process. We have derived long-term cultures of a panel of alloreactive (untransformed) clones from a rejected kidney. Among them, clone 1E7 has been chosen as a cytotoxic CD4+(CD2+CD3+TCR alpha beta+) clone proliferating against HLA-DR8 targets. This clone (clonality assessed on T cell receptor genomic rearrangements) has been grown using weekly stimulations with the kidney donor—derived EBV cell line and recombinant IL-2. Clone cultures have been adapted to mass production after optimization of culture conditions satisfying pharmaceutical requirements. This procedure warranted a reproducible source of antigen since the functional and phenotypic characteristics of the immunizing 1E7 cells remained identical through the life span of the culture. In addition the study of the total growth capacity of 1E7 cells showed consistent expansion until the 40th cell cycle, ensuring a progency that will satisfy the large-scale requirement for a clinical trial. Rabbits were injected with 100.1081e7 cells (21, 14, and 7 days before bleeding). Sera were depleted of agglutinin by red blood cell absorption and globulin antiblast (GAB) prepared by SO4Na precipitation and ion exchange chromatgraphy; 50% complement-mediated target cell lysis and 50% inhibition of E rosette formation and alloproliferation were obtained at GAB could significantly prolong skin grafts when given prophylactically. Finally GAB have been used in human recipients of kidney grafts for prophylaxis of early rejection. Results of this pilog study are given in a separate report in this issue. In conclusion we have, for the first time, set up a large-scale preparation of polyclonal globulin against a normal human alloreactive clone, and this new reagent should present several advantages over classic antilymphocyte or antithymocyte sera because it contains specificities against activation antigns and has less crossreactivity variation among batches.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Antiblast globulins (GAB) were prepared by immunization of rabbits with activated T lymphocytes (AT) derived from a rejected kidney allograft. AT consisted of a CD4+(CD3+, CD2+TCR alpha+beta+) clone cytotoxic for HLA DR8-positive targets. The immunizing cells were adapted to industrial growth conditions by repetitive stimulations with an EBV-transformed line from the kidney donor and recombinant IL-2. In the pilot study, GAB (1.0–1.5 mg/kg/day) was given in 12-hr infusions, in association with prednisone (Pred) 1 mg/kg/day and azathioprine (Aza) 2 mg/kg/day, as prophylactic treatment of rejection in 12 kidney-transplanted patients during the first 2 weeks postgrafting. GAB dosage was further adapted according to the level of circulating E-rosette-forming T cells (ERFT). Cyclosporine A (8 mg/kg/day) was given at day 14 as a monotherapy after Pred and Aza were progressively tapered. No patient died, but one kidney was lost from surgical complication. No rejection occurred under GAB treatment; 41% of patients had at least one episode in the first 3 months and 16% from 3 to 9 months. GAB side effects were minor (skin rash: 2, low grade fever: 4) except for one acute serum sickness. Platelet and white blood cell counts were unchanged, but there was a significant decrease in hemoglobin during the 2 weeks of GAB infusions. Few infectious episodes occurred (3 bacterial, 2 viral). GAB monitoring showed a dramatic drop in T11+, T3+, T4+, and T8+circulating T cells (<10% of normal values between days 3 and 14), whereas EFRT cells had a delayed and somewhat lower decrease (<10% after day 6 only). Consequently, mean GAB doses had to be raised to 1.3 mg/kg/day at day 4 and 1.6 at days 8 and 14. This pilot study suggests that this new bioreagent should be of major interest in the prophylaxis and treatment of rejection in allograft recipients. A controlled study is in progress.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

In a double-blind placebo-controlled study, the value of prophylactic anti-CMV immunoglobulin administration was evaluated in 39 kidney transplant recipients treated for rejection with rabbit antithymocyte globulin. Passive immunization completely prevented CMV-related death, although it did not reduce the incidence of CMV isolation, viremia, or disease.The effect of passive immunization was exclusively observed in CMV-seronegative recipients of a CMV-seropositive kidney donor. It could be demonstrated even when instituted when antirejection therapy was started. Seropositive recipients did not benefit from immunoglobulin treatment. Moreover, CMV-seronegative recipients of a kidney from a seronegative donor were not at risk for CMV infection at all. Therefore passive immunization should be restricted to seronegative recipients of seropositive allograft donors treated for rejection.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We reviewed the results of all percutaneous fine needle aspirations (FNA) and open lung biopsies (OLB) after bone marrow transplantation at our center (1984–1987) for the evaluation of focal lung lesions that developed or persisted despite antibiotic administration. We sought to determine the prevalence and types of infections, the yield of diagnostic procedures, and the clinical outcome of these focal lesions. Infection was documented in 78% (18/23) of all lesions and was fungal in each case. FNA detected fungal lung infection with a sensitivity of 67% (10/15) but had a negative predictive value of only 50% (5/10). Complications occurred in 15% of FNA. OLB without prior FNA was performed in 6 cases and demonstrated fungal infections in 5. Overall, seven of the 18 patients with localized invasive fungal lung disease recovered after antifungal therapy. This study demonstrates that focal lung lesions that develop or persist despite antibiotics afte BMT are most often fungla. FNA may safely identify these localized infections in selected patients and with appropriate treatment recovery may be achieved.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

From November 1985 to August 1987, 22 children underwent orthotopic liver transplantation (OLT). Primary cytomegalovirus (CMV) infection was observed in 3 of 10 seronegative recipients (30%). It was severe in 2 cases, which were treated successfully by a combination of DHPG and CMV hyperimmune globulin. From September 1987 to August 1988, a virologic survey was undertaken. It enabled us to take prophylactic measures and to make an early diagnosis of CMV infection, permitting early antiviral treatment. During this period, 26 children received liver grafts. Nine of 13 seronegative recipients (69, 2%) developed primary CMV infection. Seven had received immunoprophylaxis and 8 were treated by DHPG. None had severe disease and all improved rapidly.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We compare the expression of donor class I and class II major histocompatibility complex antigens in DA kidney grafts transplanted to PVG recipients treated by different protocols of donor-specific immunosuppression. MHC expression was evaluated using donor-specific antibodies and assays by immunohistology and quantitative absorption analysis. PVG recipients were either untreated or treated by (A) twice-weekly intravenous injections of 0.5 ml DA blood for 12 weeks; (B) 0.5 ml DA blood intravenously at 7 days pregraft; (C) as for (B), but with the addition or oral cyclosporine at 10 mg/kg/day from the day of grafting; and (D) passive enhancement with DA anti-PVG serum. Grafts were assessed at 3, 5, and 7 days after transplantation. In untreated controls at day 3, there is a periarteriolar leukocyte infiltrate, weak or absent class II induction, but strong class I induction. Class II induction in untreated controls is maximal at day 5. We confirm that active enhancement by blood transfusion, even using the intensive protocol of twice-weekly transfusions for 3 months, results in accelerated leukocyte infiltration and accelerated donor class I and class II MHC induction. At day 3, there is an intense, diffuse leukocyte infiltration and maximal class II induction. Cyclosporine treatment of blood-transfused recipients reduced the leukocyte infiltration and MHC induction to levels seen in untreated controls—i.e., the accelerated MHC induction caused by the transfusion was partially reversible by cyclosporine. In passively enhanced recipients, leukocyte infiltration and class I MHC induction were similar to untreated controls. However, class II induction was much delayed, not being evident until day 7.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

In continuation of our studies using UV-B-irradiated DST and donor leukocyte (DL) recipient pretreatment to induce specific unresponsiveness to organ allografts, we have examined the relative contributions of splenic lymphocyte populations and T lymphocyte subsets in the induction of immunologic unresponsiveness. Our data show that enriched populations of MHC class II-positive B lymphocytes and the W3/25+T cell subset obtained from splenic leukocytes using immunoadsorbent columns in conjunction with mAbs led to indefinite graft survival (>100 days) in the Lewis-to-ACI rat cardiac allograft model. In contrast, pretreatment with T lymphocytes or the 0°8+T subset was relatively ineffective in prolonging cardiac allograft survival. In addition, third-party (W/F) W3/25+T cell recipient pretreatment did not influence the survival of Lewis cardiac allografts in ACI recipients, thus confirming the specificity of pretreatment with the T cell subset in graft prolongation. Furthermore, we have examined the underlying mechanisms of donor-specific unresponsiveness induced by donor spleen cells, B lymphocytes, and W3/25+T cells using adoptive transfer assays. Serial adoptive transfer studies demonstrated the presence of 0°8+suppressor T cells in the spleens of unresponsive recipients bearing well-functioning cardiac allografts and of serum “suppressor factors” that have the capacity for specifically prolonging donor-type test graft survival in naive syngeneic rats. Our findings suggest that the induction of specific unresponsiveness in this model is dependent on a sequential collaboration between the appearance of donor-specific serum factor(s) (humoral phase) and donor-specific suppressor T cells (cellular phase). These results may be potentially useful in planning future strategies for the induction of unresponsiveness to clinical organ allografts by immunologic manipulation of the host with MHC class II-positive B cell and CD4+T cell clones.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID