Cytomegalovirus infection in patients with renal transplants: potentiation by antithymocyte globulin and an incompatible graft

Fifty-six of 67 patients with antibody to cytomegalovirus before transplantation shed cytomegalovirus from urine and/or saliva postoperatively. Symptomatic reactivation occurred in 17 (25%) patients, five of whom had pneumonitis. The symptomatic patients were more likely to have received a cadaver kidney (P = 0.004) and high-dosage antithymocyte globulin (P = 0.003) and to be viremic (P < 0.0001), compared to patients with silent infection. Forty-eight of 49 patients treated with antithymocyte globulin received cadaver or parent donor kidneys. Twenty-four were given a low-dosage intramuscular regimen, and 25 received a higher dosage intravenously. In the latter group 48% experienced symptomatic reactivation adn 48% viremia, compared to 21% and 17%, respectively, in the former group (P < 0.05 for both comparisons). There were no symptomatic cytomegaloviral infections among 18 patients not treated with antithymocyte globulin, all of whom received related donor kidneys. Renal transplant patients who receive both a poorly matched graft and antithymocyte globulin are at increased risk of morbidity due to cytomegalovirus.     

Treatment of severe aplastic anemia

A total of 100 patients with severe aplastic anemia were treated and evaluated in a prospective study at our hospital between January 1976 and October 1983: 28 patients had an HLA-identical sibling donor and were treated with bone marrow transplantation, and 72 patients without an HLA-identical sibling donor were given antilymphocyte globulin followed by oral low-dose androgen therapy. At 1 1/2-9 years after treatment, 13 patients (46%) survive in the transplant group and 45 patients (75%) survive in the second group. All except one in the second group have self-sustaining hematopoiesis without need for transfusions. There is one major difference between the two therapies. Marrow transplantation restores bone marrow function completely and no late hematologic complications have been seen in this group. The majority of patients treated with antilymphocyte globulin in contrast have residual abnormalities of hematopoiesis: macrocytosis, mild granulocytopenia, and mild thrombopenia. Relapse (11 of 72 patients) and clonal hematologic disorders, such as paroxysmal nocturnal hemoglobinuria (four patients) and leukemia (one patient) can occur years after complete bone marrow reconstitution with antilymphocyte globulin. These late disorders are of concern. Despite this, we conclude that antilymphocyte globulin treatment is an effective therapy with low early mortality and morbidity and a high chance for a long, sustained remission. Results are better or at least equivalent to bone marrow transplantation and patients with donors should be given the option of transplant or antilymphocyte globulin.     

Treatment of severe aplastic anemia with combined immunosuppression (antithymocyte globulin and high-dose methylprednisolone)

Fifteen patients with transfusion-dependent severe aplastic anemia (SAA) were treated with combined immunosuppression consisting of horse-antithymocyte globulin (ATG; Atgam, Upjohn) and high-dose 6-methylprednisolone (MP). Oxymetholone was scheduled for 2 years but was discontinued in 7 patients after 10-385 days due to liver toxicity. Serious side effects usually seen in ATG monotherapy were rare during combined immunosuppression. Currently 12 of 15 patients are alive 110-1,275 days (median 475.5) after start of treatment. One patient has received too short treatment to be evaluated. All the others are transfusion-independent. Three patients died; two from septicemia before hemopoietic recovery could be expected and one after relapse. Our results confirm that the addition of high-dose MP abrogates the side effects of ATG monotherapy, and the addition of MP does not counteract, but rather enhances the beneficial effect of ATG in SAA. We recommend combined immunosuppressive treatment with ATG and high-dose MP as a highly feasible, safe and effectful therapy for patients with transfusion-dependent SAA.     

Immunosuppression as initial treatment for gold induced aplastic anemia

Three patients who received antithymocyte globulin therapy for severe aplastic anemia due to gold therapy are described. In 2 patients the hemoglobin, white blood cell count and neutrophils were normal and platelet counts exceeded 100 X 10(9)/1 more than 2 years after treatment. The 3rd patient did not respond to antithymocyte globulin or to cyclosporine therapy; subsequent allogeneic bone marrow transplantation resulted in satisfactory engraftment at 12 months. In all 3 patients the arthritis was improved after the episode of marrow aplasia and its treatment. Including these 3 patients, 12 reported patients with severe aplastic anemia due to gold have now been treated with antithymocyte globulin; 8 have shown significant improvement. These results are better than those reported for any other treatment. Antithymocyte globulin may be optimal initial treatment for this serious disorder.     

Long-term outcome after immunosuppressive therapy with horse or rabbit antithymocyte globulin and cyclosporine for severe aplastic anemia in children

Some prospective studies showed that rabbit antithymocyte globulin was inferior to horse antithymocyte globulin as first-line therapy for patients with severe aplastic anemia. We retrospectively analyzed the clinical outcome of 455 children with severe aplastic anemia who received horse antithymocyte globulin (n=297) or rabbit antithymocyte globulin (n=158) combined with cyclosporine as first-line therapy between 1992 and 2010. The response rates were comparable between the horse and rabbit antithymocyte globulin groups at 3 months [46% (136/294) versus 42% (66/153), P=0.55] and 6 months [60% (178/292) versus 55% (87/143), P=1.0]. Using multivariate analysis, differences in antithymocyte globulin preparations were not associated with response rates. However, 2-year and 10-year overall survival rates in the horse antithymocyte globulin group were significantly better than those in the rabbit antithymocyte globulin group (2-year overall survival: 96% versus 87%, 10-year overall survival: 92% versus 84%, P=0.004). On the basis of multivariate analysis, use of rabbit antithymocyte globulin was a significant adverse factor for overall survival (hazard ratio = 3.56, 95% confidence interval, 1.53 – 8.28, P=0.003). Rabbit antithymocyte globulin caused more profound immunosuppression, which might be responsible for the higher incidence of severe infections. Considering that there are no studies showing the superiority of rabbit antithymocyte globulin over horse antithymocyte globulin, horse antithymocyte globulin should be recommended as a first-line therapy. However, our results justify the use of rabbit antithymocyte globulin as first-line therapy if horse antithymocyte globulin is not available.     

Do androgens enhance the response to antithymocyte globulin in patients with aplastic anemia? A prospective randomized trial

We analyzed the effect of antithymocyte globulin (ATG) with or without androgens in 121 patients with aplastic anemia. Fifty-three patients with moderate to severe aplastic anemia were prospectively randomized to receive ATG with or without oral androgens. Eleven of 26 patients (42%) receiving ATG plus androgen responded, including three complete and eight partial responses. Twelve of 27 patients (44%) receiving ATG plus placebo responded, including five complete and seven partial responses. The difference in response rates was not significant (P greater than .9). Survival was also comparable in the two groups; for patients with severe aplastic anemia, actuarial survival at two years was 55% +/- 24% (95% confidence interval) in patients receiving ATG plus androgen compared with 50% +/- 24% in the ATG plus placebo group (P = .65). Furthermore, results in both groups were indistinguishable from those obtained in 68 historical controls receiving ATG without androgens. These data indicate that androgens are not required in order to respond to antithymocyte globulin and the addition of androgens, as used in this trial, did not significantly improve response rates to ATG treatment.     

活动性炎症性肠病患者蛋白质和脂代谢的变化

目的 比较炎症性肠病患者及正常对照者之间蛋白质和脂代谢的差异,研究这些差异与疾病活动性及病变部位的关系.方法 回顾性研究1995至2007年溃疡性结肠炎(UC)195例、克罗恩病(CD)76例及正常对照者97名的蛋白质和脂代谢资料.同时评价临床疾病活动指数,红细胞沉降率(ESR)和C-反应蛋白(CRP)水平.性别分层分析蛋白质和脂代谢指标的改变,同时分析蛋白质和脂代谢的改变与疾病活动性及病变部位的关系.结果 UC患者的ESR与血清白球比呈负线性相关(β=-0.521,P＜0.01),与α2-球蛋白呈正线性相关(β=0.319,P＜0.01);CD患者血清球蛋白与ESR(β=0.558,P＜0.01)以及cRP(β=0.424,=P0.01)呈正线性相关.UC患者间因病变部位不同,血清白球比、白蛋白和总胆固醇水平存在显著差异,其中直乙结肠炎患者该三项显著高予其他类型的UC患者(P值分别=0.003、0.005、0.038).CD患者间亦因病变部位不同,血清球蛋白水平存在显著差异,仅累及结肠者的血清球蛋白水平显著高于单纯小肠受累者(P=0.029).结论 UC患者血清白球比和α2-球蛋白的异常程度可作为炎症活动性的预测因素;CD患者血清球蛋白增高预示疾病严重程度活动性增加,累及小肠的CD患者相对仅累及结肠的CD患者而言存在更为严重的营养缺失.     

SEX HORMONES IN MALE PATIENTS WITH CHRONIC RENAL FAILURE. I. THE PRODUCTION OF TESTOSTERONE AND OF ANDROSTENEDIONE

The production of testosterone (Te) and androstenedione (A) has been studied in twenty-three patients with chronic renal failure. Four of the patients were being prepared for haemodialysis (HD) treatment — non-HD patients — nineteen were on chronic HD treatment, five of whom had been nephrectomized bilaterally. Data are presented on plasma Te and A levels, on the response to HCG and on changes after HD. The Metabolic Clearance Rate (MCR), blood production rate and the mutual interconversion of both steroids were determined together with the plasma sex hormone binding globulin capacity. In all groups of patients, plasma levels of Te were low and stimulation with HCG resulted in an insufficient increase in plasma Te levels, indicating Leydig cell deficiency in chronic uraemic males. In addition, a tendency to increased metabolic breakdown of Te was observed, most probably caused by a deficient synthesis of the sex hormone binding globulin. In patients with high peripheral degradation of Te, the testicles were able to produce about normal amounts of Te. In the non-HD patients an increase in the MCR and blood production rate of A was found. This may be due to an alteration in the testicular steroid secretion. The other groups of patients did not show differences in the production of A when compared with normal males. No significant changes in plasma levels of Te and A were observed during HD treatment. The picture emerging from our data is similar to the one observed in population groups with severe protein malnutrition.     

Induction of an inhibitor antibody to factor XI in a patient with severe inherited factor XI deficiency by Rh immune globulin

In this paper, we report an inhibitor antibody to factor XI (FXI) in a woman with severe inherited FXI deficiency, induced by FXI present in an Rh immune globulin preparation. The patient is homozygous for the Glu117Stop mutation, associated with a FXI level of less than 1 U/dL. Unlike all previously described patients with severe FXI deficiency and an inhibitor, the patient had never been exposed to blood products. Following 3 injections of Rh immune globulin during pregnancy, she developed an inhibitor to FXI (8 Bethesda units) that was shown to bind specifically to FXI and inhibit factor IX cleavage by purified FXIa. The administered Rh immune globulin and 2 other similar products were shown to contain FXI. Clinicians should be aware of the potential for immunization of severely FXI-deficient patients by FXI present in Rh immune globulin preparations.     

AN IMPROVED METHOD FOR THE ESTIMATION OF RELATIVE BINDING CONSTANTS OF T4 AND ITS ANALOGUES WITH SERUM PROTEINS

A new method is reported for the determination of the binding constants of homologous ligands relative to that of the parent ligand. The technique minimizes the effects of random and bias errors inherent in absolute methods and obviates the need to quantitate the radiolabelled tracer concentration. In addition, it is likely to be of general applicability for monovalent proteins. The method has been applied in the determination of the binding constant (relative to that of T4) of the T4-analogue tracer used in the Amerlex free T4 radioimmunoassay, in respect of its binding to both T4 binding globulin and prealbumin. The binding constants of the analogue (relative to T4) were approximately 3% for both proteins. These levels were judged unlikely to interfere significantly with the measurement of free T4 in serum samples from patients with very wide variations in concentration of either T4 binding globulin or prealbumin.     

Prevention of cytomegalovirus infection by cytomegalovirus immune globulin after marrow transplantation

In an effort to prevent cytomegalovirus infection among seronegative patients having marrow transplants, a globulin with high antibody levels against cytomegalovirus was given before and for 11 weeks after transplantation in a randomized trial. Among 36 patients who received no prophylactic granulocyte transfusions, globulin recipients had significantly fewer infections than controls (2 of 17 versus 8 of 19, p = 0.05 by Fisher's exact test and p = 0.03 by Mantel-Cox test). Conversely, infection rates were high and unchanged by globulin use among patients who received granulocytes from seropositive donors (7 of 8 recipients versus 6 of 7 controls). The lack of effect of the globulin among patients receiving transfusions of granulocytes from seropositive donors may suggest that the dose of antibody was insufficient or that antibody is ineffective against virus transmitted in granulocytes. We conclude that cytomegalovirus infection can be prevented by immunoprophylaxis in seronegative patients having marrow transplants who are not given granulocyte transfusions.     

The role of antilymphocyte globulin in the treatment of chronic acquired bone marrow failure

Antilymphocyte globulin is an immunoglobulin preparation prepared from heterologous serum after the animal (horse or rabbit) has been immunised with human lymphocytes, obtained from the thymus (antithymocyte globulin, ATG) or thoracic duct (antilymphocyte globulin, ALG). The rationale for the use of ALG in the treatment of chronic acquired marrow failure is based on its immunosuppressive activity and the fact that a proportion of cases of bone marrow failure, whether affecting single or multiple haemopoietic cell lines are due to immune-mediated suppression of haemopoiesis. In addition, in vitro studies have shown that ALG also has an immunostimulatory effect on lymphokine and haemopoietic growth factor production, and may therefore directly stimulate haemopoietic progenitor cells. ALG has been used for the treatment of aplastic anaemia and acquired chronic marrow failure affecting single cell lines namely pure red cell aplasia (PRCA), amegakaryocytic thrombocytopenia and chronic neutropenia due to immune inhibition of granulopoiesis ('acquired white cell aplasia'). ALG is used for treatment of non-severe aplastic anaemia (NSAA) and in those cases of severe aplastic anaemia (SAA) where allogeneic transplantation is not possible or is not indicated. Treatment with ALG results in 75% long term survival for NSAA and 40-50% for SAA although there is a very severe subgroup of SAA defined by peripheral blood neutrophils of less than 0.2 x 10(9)/l who rarely benefit from ALG therapy. For those patients who do not respond a second course of ALG can be given later using ALG from a different animal source.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison between horse and rabbit antithymocyte globulin as first-line treatment for patients with severe aplastic anemia: a single-center retrospective study

The best antithymocyte globulin preparation for first-line immune suppression in patients with severe aplastic anemia is still not clear. The aim of this study was to compare hematological response and overall survival in patients submitted to horse or rabbit antithymocyte globulin as first-line treatment for severe aplastic anemia. We retrospectively compared 71 consecutive patients with severe aplastic anemia, classified according to the antithymocyte globulin preparation. Analyses included variables related to patients and to immune suppression. Forty two patients (59.1%) received horse and 29 (40.9%) rabbit antithymocyte globulin. Response rates were higher at 6 months in patients submitted to horse in comparison to rabbit antithymocyte globulin (59.5% versus 34.5% respectively, p = 0.05). Median time to response was similar between the two groups (99 versus 88.5 days, respectively, for horse and rabbit antithymocyte globulin; p = 0.98). Overall survival at 2 years was significantly higher in patients submitted to horse in comparison to rabbit antithymocyte globulin (78.4% versus 55.4%, p = 0.03). Post-treatment response was strongly associated with survival at 2 years (97% in responders versus 41.2% in non-responders, p < 0.001). Use of rabbit antithymocyte globulin was an independent predictor of death (odds ratio 2.5; 95% confidence interval 1.03–6.04; p = 0.04). Rabbit antithymocyte globulin was associated with a significant and prolonged lymphopenia in comparison with horse antithymocyte globulin. Our data suggest the superiority of horse over rabbit antithymocyte globulin as first-line treatment for severe aplastic anemia, both regarding hematological response and survival.     

Predictive value of serum globulin levels for the extent of hepatic fibrosis in patients with chronic hepatitis B infection

The mechanism underlying disease progression in hepatitis B virus (HBV) infection is unknown. Immunoglobulins stimulate the proliferative activity of rat hepatic stellate cells in vitro. A strong association was found between serum immunoglobulin levels and hepatic fibrosis in patients with hepatitis C virus infection. Our objective was to determine if the same index could also be used in patients with chronic HBV infection. The records of 100 patients with biochemical, serological, virological and histological evidence of chronic HBV infection were reviewed for background factors and serum globulin and immunoglobulin levels. Mean (+/-SD) patient age was 44.0 +/- 14.7 years; 80 (80%) were male. Of the factors found to be significant on univariate analysis, the only significant predictors of severe hepatic fibrosis (stage > or = 2) on multivariate analysis were serum globulin level [odds ratio (OR) 5.97, 95% confidence intervals (CI) 1.82-19.53, P = 0.0004], platelet count (OR 0.98, CI 0.97-0.99, P = 0.001), and immunoglobulin G (IgG) level (OR 1.003, CI 1.000-1.007, P < 0.042) but not IgA, alkaline phosphatase, albumin or international normalized ratio. For each increase of 0.33 mg/dL in serum globulin, there was a 0.5 point increase in the stage of hepatic fibrosis. There appears to be a strong association between levels of serum globulin and IgG and extent of hepatic fibrosis in patients with chronic HBV infection. They can serve as noninvasive markers of hepatic fibrosis and, if confirmed, have important implications for the management of patients with chronic HBV infection.     

Mechanism of the Albumin Agglutination Phenomenon

Summary. The albumin agglutination phenomenon is due to antibodies which cause agglutination of all human red cells when these cells are suspended in an albumin medium. Two sera with this property were studied. We suggest that the reaction is due to non-specific adsorption of antigen-antibody complex onto red cells. The antibody is a gamma globulin directed at albumin which has been altered by the addition of acetyl tryptophanate or caprylate. These chemicals are added as stabilizers in the manufacture of albumin to prevent denaturation when the albumin is heated.
Since unaltered (native) albumin does not react with these antibodies, blood or plasma transfusion to patients with this serologic abnormality should present no unusual hazard. A non-reactive albumin should be used in crossmatching blood for such patients. Therapeutic human serum albumin and plasma products containing stabilized albumin are probably contraindicated in these patients.     

人工肝支持系统对肝移植围手术期肝衰竭患者Gc球蛋白的影响

目的 研究人工肝支持系统(血浆置换联合连续性静脉-静脉血液透析滤过)对肝衰竭患者血清Gc球蛋白的影响,探讨血清Gc球蛋白在肝衰竭患者病情预后评估中的意义.方法 将81例肝衰竭患者按治疗方案不同分为人工肝治疗组(43例),常规治疗组(38例);然后再分为人工肝治疗有效组(A组)、人工肝治疗无效组(B组)、常规治疗有效组(C组)和常规治疗无效组(D组),比较各组间治疗前后及治疗过程中Gc球蛋白的变化,分析Gc球蛋白分别和白细胞介素(IL)-18、IL-10、IL-4、肿瘤坏死因子α、内毒素、一氧化氮合酶、可溶性血管细胞黏附分子1、可溶性细胞间黏附分子1之间的关系.根据资料不同分别采用t检验、单因素方差分析(one-way ANOVA)、Pearson相关分析或x2检验.结果 (1)人工肝治疗组好转率为67.44%(29/43),常规治疗组治疗好转率为34.21%(13/38,P＜0.01).(2)人工肝治疗组治疗后Gc球蛋白显著升高,治疗前后比较,差异有统计学意义(P＜0.01);治疗后与常规治疗组治疗后比较,差异有统计学意义(P＜0.01),其中A组和C组治疗后明显升高,但A组治疗后较C组治疗后升高明显,两组间差异有统计学意义(P＜0.01);与B组和D组治疗后比较,差异有统计学意义(P＜0.01);各组肝衰竭患者血清Gc球蛋白水平的动态观察结果显示:A组和C组患者血清Gc球蛋白水平呈现由低到高的变化趋势;B组和D组患者的血清GC球蛋白水平波动,但无显著升高(P＞0.05).(3)Gc球蛋白和IL-4、IL-18和肿瘤坏死因子α、一氧化氮合酶、可溶性血管细胞黏附分子1、可溶性细胞间黏附分子1成负相关关系,而与IL-10之间无相关性.结论 人工肝支持系统能提高肝衰竭患者血清Gc球蛋白的水平,并最终可提高肝衰竭抢救成功率,改善预后.Gc球蛋白水平可作为临床转归的预测指标.

Abstract：

Objective To investigate the effects of artificial liver support system(plasma exchange combined with continuous veno - venous hemodiafiltration, PE + CVVHDF) on Gc globulin in patients with liver failure. Methods 81 patients with liver failure were divided into 4 groups according to the treatment protocols and indicators such as liver function and clinical symptoms. Totally 29 effective cases and 14 ineffective cases in the ALSS group versus 15 effective cases and 23 ineffective cases in the medical group were included. Finally the changes of Gc globulin were observed in four subgroups before and after treatment.The correlation between Gc globulin and IL-10, IL-4, IL-18, TNF c, endotoxin, NO, sVCAM-land sICAM-1 were analyzed by Pearson correlation analysis. Results The effectiveness rate was 67.44% in ALSS group and 34.21% in the medical treatment (P ＜ 0.01). Gc globulin, one of liver cell protection proteins was notably increased following the artificial liver treatment as compared with the increase in the medical treatment (P ＜0.01). The time-response curve of Gc globulin level had a significant upward trend in the effective group as compared to no significant rise in the ineffective group. Moreover, the Gc globulin was negatively correlated with IL-4, IL-18, TNFα, SVCAM-1, SICAM-1 and NO. In contrat, no correlation existed between Gc globulin and IL-10. Conclusion The treatment with artificial liver can improve the outcome of the patients with liver failure. The level of Gc globulin was correlated with the curative effect and thus may be used as a potential indicator for curative effect forcast in the patients with liver failure.     

Impaired binding properties of thyroxine-binding globulin in hepatocellular carcinoma and chronic liver disease.

To determine the factors underlying the apparent reduction in binding ability of thyroxine-binding globulin in hepatocellular carcinoma, hormone-binding characteristics were further examined in patients with this disease and in control subjects. No differences in affinity constants with respect to triodothyronine or serum thyroxine-binding globulin from hepatocellular carcinoma, cirrhotic and normal subjects were found. The affinity for thyroxine was significantly reduced in hepatocellular carcinoma (0.41 +/- 0.13 x 10(10) mol-1) and cirrhotic (0.65 +/- 0.1 x 10(10) mol-1) patients compared with normal subjects (0.94 +/- 0.7 x 10(10) mol-1). Investigations carried out on liver tissue obtained from patients with hepatocellular carcinoma and chronic liver disease showed that thyroxine-binding globulin within tumor tissue was elevated and bound less exogenous tracer hormone compared with that obtained from nontumor tissue. Tumor-derived thyroxine-binding globulin with altered binding properties is, at least partly, responsible for the abnormal behavior of the serum protein in patients with hepatocellular carcinoma.     

Aplastic anaemia: pathogenetic mechanisms and treatment with special reference to immunomodulation.

Aplastic anaemia (AA) has been defined as a syndrome in which the presence of pancytopenia is accompanied by marrow hypocellularity. Ample laboratory data and clinical observations continue to make immune mediation of bone-marrow failure an attractive hypothesis. Recent progress in the practice of bone-marrow transplantation has led to a survival rate of approximately 80% in the best cases, but such a treatment is only amenable in young patients (less than 45-50 years) with HLA-identical bone-marrow donors. Anti-lymphocyte and thymocyte globulin treatment has been surprisingly effective for AA, resulting in transfusion independence in 40-80% of patients. The mechanism of action is unknown, although effects on immunosuppression appear to be the most likely candidates. Long-term results for patients receiving cyclosporin A treatment will soon be available, and preliminary data show an effect similar to that of antithymocyte globulin. In contrast to successful bone-marrow transplantation, improvement following immunomodulation leaves quantitative abnormalities in all haematopoietic cell lines, and patients are prone to develop clonal (malignant) disease.     

Management of hepatitis B in liver transplant patients

Recent therapeutic advances have allowed for routine transplantation of patients with hepatitis B. The first major breakthrough was the use of hepatitis B immune globulin, which reduced posttransplantation hepatitis B recurrence rates to approximately 20%. More recently, the nucleoside analogues lamivudine and adefovir have shown efficacy in the treatment of hepatitis B both before and after liver transplantation. Management strategies are evolving that include initiation of a nucleoside analogue pretransplantation in patients with active viral replication. Combination therapy with hepatitis B immune globulin and a nucleoside analogue is being used posttransplantation. In addition, there is interest in the use of therapeutic vaccination posttransplantation. In this report, we review strategies for managing HBV in the setting of liver transplantation and detail data regarding patient outcomes.     

Epstein-Barr virus infection in renal transplant recipients. Effects of antithymocyte globulin and interferon

We studied Epstein-Barr (EB) virus excretion and antibody in 41 renal transplant recipients enrolled in a placebo-controlled trial of human leukocyte interferon. Half the patients were also treated with antithymocyte globulin. Epstein-Barr virus excretion occurred more often in recipients of cadaver kidneys (P = 0.03) and those receiving antithymocyte globulin (P = 0.04) and less often in patients given interferon (P = 0.08). Antibody to viral capsid antigen increased fourfold or more in 12 of 22 patients treated with antithymocyte globulin and in none of the non-antithymocyte globulin-treated group (P = 0.0002). Antibody to the restricted component of early antigen rose fourfold or more in eight patients and appeared related to the occurrence of syndromes similar to those attributed to cytomegalovirus in transplant recipients. We conclude that increasing immunosuppression augments the rate of EB virus reactivation and that EB virus may be an important pathogen in heretofore ill-defined syndromes.