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Kidney transplantation in rhesus monkeys. Matching for D/DR antigens, pretransplant blood transfusions, and immunological monitoring before transplantation.

The effect of matching for D/DR antigens and of three pretransplant blood transfusions on kidney allograft survival was investigated in unrelated rhesus monkeys treated with standard immunosuppression. A control group consisting of host-donor combinations mismatched for one or two DR antigens (mixed lymphocyte culture (MLC) positive) and not receiving transfusions showed a MST of 13 +/- 1.2 days with a range from 9 to 22 days. The administration of pretransplant blood transfusions led to a MST of 28 +/- 5.4 days with 5 of 12 animals showing survival times of more than 22 days (i.e., a bimodal distribution of survival times). Recipients matched with their donors for two DR antigens and given transfusions showed an even better MST of 39 +/- 4.0 days. Under these conditions, MLC-negative combinations fared slightly better than MLC-positive ones: only 1 of 10 animals showed a survival time of less than 22 days and kidney function in the first weeks after transplantation was significantly better. When mixed lymphocyte reactions (MLC reactivity) between host and donor before and after the transfusions were compared, it was possible to predict to some extent the eventual fate of an allograft: increased mixed lymphocyte reaction predicted relatively short survival times, decreased mixed lymphocyte reaction relatively long ones (P less than 0.01).

Animals↗

Immunological monitoring of melanoma patients on BCG immunotherapy. I. Enzyme-linked immunosorbent assay of human sera after BCG-treatment.

Purified lipopolysaccharide (LPS), isolated from BCG and purified protein derivative of tuberculin (PPD) were used as antigens in an enzyme-linked immunosorbent assay (ELISA) of sera from patients with malignant melanoma undergoing immunotherapy with BCG. It was found that LPS and ELISA are useful tools in the monitoring of humoral immune response against BCG.

Antibody Formation↗

[Immunological monitoring of brain tumors--prognosis and cellular immunity of patients with brain tumors].

The usefulness of in vivo skin tests for reaction to purified protein derivative (PPD) and phytohemagglutinin (PHA) for assessment of cell mediated immunity was investigated among 31 patients with brain tumors. These included 22 gliomas and 9 metastatic brain tumors. Each patient was administered intradermal injections of 0.05 micrograms PPD and 0.5 micrograms PHA, and erythema was observed in each case. A positive reaction (erythema diameter greater than 10 mm) to PPD was observed in 8 (74%) of 11 low grade gliomas, 3 (27%) of 11 malignant gliomas and 6 (67%) of 9 metastatic brain tumors. A positive reaction (erythema diameter greater than 25 mm) to PHA was observed in 8 (74%) of 11 low grade gliomas, 4 (36%) of 11 malignant gliomas, and 6 (67%) of 9 metastatic brain tumors. In repeated PHA skin reaction tests conducted at intervals of one month, the reaction of the patients depended on their clinical state. Thirteen of the patients died. The PHA skin reaction of 7 of the 13 patients who survived for more than 6 months was all negative 6 months prior to death, and continued and repeated reaction tests did not result in a positive finding except for one patient with malignant glioma. In 10 of the 13, the PHA skin reaction was negative one month prior to death, and the final test result was negative for 11 of the 13.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Immunological monitoring in lung cancer: use of the leukocyte migration inhibition assay.

The agarose microdroplet leukocyte migration inhibition assay has been applied to the management of patients with lung cancer. Sera of patients with various stages of the disease were assayed in the indirect LMI system for their influence on the LIF production of normal leukocytes. A probably cell-mediated immunity blocking activity could be detected both in the serum of patients with inoperable tumours and in that of operable patients before and two weeks after surgery. The activity, however, disappeared in two thirds of the cases in about 6 months after surgery. The immune competence of patients with inoperable tumours was investigated before and during combined chemotherapy. A positive correlation was established between the tuberculin skin reactions and the leukocyte migration inhibition obtained in the direct LMI assay against PPD, but only in the presence of autologous serum. Sera of patients were also tested for putative in vivo LIF activity by their effect on the migration of autologous leukocytes. A significant correlation between anergy to PHA, as evaluated by skin testing, and the migration inhibition caused by sera was found. When, however, sera from healthy persons and from patients with chronic bronchitis or lung cancer were compared for their effect on the migration of normal leukocytes, no difference could be detected among the three groups. Single doses of the drugs temporarily weakened the skin reactions to PHA and the migration inhibition to PPD in autologous serum, but activity was restored when the drug influence had ceased.

Binding, Competitive↗

The patient with multiple organ system failure: immunologic monitoring.

The patient with multiple organ system failure is commonly suffering from the systemic effects of postsurgical or post-traumatic sepsis. An understanding of the role of the systems that mediate infection and produce much of the clinical picture is an important base for management and for future research. The use of the term "immunity" in relation to this process refers to two general response systems, which differ in some important aspects. The so-called cellular immune system, which embodies specific and preprogrammed responses, centers on the various populations of lymphocytes. Although there is considerable knowledge about their functional biology, this is perhaps more relevant to the transplantation and cancer areas than it is to trauma and surgical infection. Conversely, there is less known about the mediator systems, which seem to be more closely involved in the patient with multiple organ system failure. The relatively nonspecific responses of the circulating fixed macrophages, particularly granulocytes and monocytes, together with complement and other opsonins, clearly need considerable further investigation to define their critical role. This review attempts to outline common knowledge about the response systems that mediate systemic and organ failure in sepsis, and it points out certain areas that seem to hold promise for advances in the management of such patients.

Antibody Formation↗

[Immunologic monitoring of HIV-positive patients. T-lymphocytes and their subpopulations in various clinical stages of HIV infection].

The authors evaluate T-lymphocytes and their sub-populations, the immunoregulating index and white cell haemogram in patients in different clinical stages of HIV infection. They discuss the importance of the investigated parameters, in particular the number of CD4+ T-lymphocytes in the peripheral blood stream as a laboratory criterium for the development of the disease. From the paper ensues that evaluation of the number of CD4+ T-lymphocytes in the peripheral blood stream can help to estimate the time of the primary infection and the selection of an optimal time for starting azidothymidine therapy, but alone it does not suffice for establishment of the prognosis of the development of the HIV infection.

Adolescent↗

The use of therapeutic drug monitoring to optimise immunosuppressive therapy.

Most experience of the therapeutic drug monitoring of immunosuppressive agents has been acquired in the field of solid organ transplantation; however, agents such as cyclosporin (cyclosporin A) are being increasingly utilised for the management of autoimmune diseases. Cyclosporin is the most widely studied immunosuppressant, but in spite of this many controversies still exist as to the optimum strategy for monitoring this drug. Owing to its widely variable pharmacokinetics and metabolism, and the absence of a simple method to measure therapeutic effectiveness, many factors should be considered. In most circumstances, measuring whole blood through concentrations of cyclosporin with a specific assay methodology is warranted. In addition, knowledge of other factors that may alter the pharmacokinetics (such as liver function, concomitant food or medications, gastrointestinal status, and time since transplantation) should be taken into account so that therapy can be appropriately adjusted. Other methods of monitoring have been investigated, such as AUC (area under the concentration-time curve) monitoring and immunological monitoring. However, further refinement of these techniques and greater experience with their efficacy must be accumulated before their role in the monitoring of cyclosporin can be defined. Tacrolimus, like cyclosporin, shares many of the difficulties in monitoring for efficacy and toxicity due largely to the variable pharmacokinetics; similarly to cyclosporin, whole blood through concentration monitoring should be utilised in combination with knowledge of the factors that may affect the pharmacokinetics. Muromonab CD3 (OKT3) is a monoclonal antibody used for the treatment and prophylaxis of acute allograft rejection. Several immunological monitoring techniques have been investigated for this agent. Monitoring CD3+ levels can assist clinicians in determining therapeutic efficacy, while measuring antimuromonab CD3 antibody titres can help determine if xenosensitisation has occurred, causing therapeutic ineffectiveness. The clinical monitoring of azathioprine, one of the first immunosuppressive agents used in transplantation, has historically been limited to monitoring complete blood counts for bone marrow suppression. However, newer techniques measuring intracellular DNA nucleotides appear to be promising. The new immunosuppressants on the horizon include mycophenolate mofetil and rapamycin. The clinical experience with therapeutic drug monitoring of these 2 compounds is scant in the literature; however, both agents have demonstrated efficacy in preventing or treating allograft rejection while maintaining a relatively well tolerated toxicity profile in recent clinical trials. Routine monitoring does not appear to be warranted for immunosuppressive therapy in autoimmune diseases.

Autoimmune Diseases↗

Laboratory indicators for monitoring HIV disease.

Immunological monitoring of disease progression following HIV infection and seroconversion illness, latency and AIDS, not only helps in the basic investigation of the natural history of the viral infection in man, but also can assist in prognosis and treatment of AIDS-defining illnesses. However, outside clinical trials, these tests should be selected and used in clinical practice only if they are validated as relevant and effective. The absolute CD4+ T-helper lymphocyte count, measured by flow cytometry, has emerged as the best available investigation, but needs care in sampling due to diurnal and circadian rhythms, effects of age, pregnancy, therapy, intercurrent infections and technique. Sampling should provide a baseline and trends-monthly intervals initially, then quarterly in uncomplicated cases. Thresholds may be given for counts (e.g. 200/microliter) below which prophylaxis against pneumocystis pneumonia should be administered, and repeating persistently low counts (e.g. below 50/microliter) is seldom helpful in practice. Serum levels of beta-2 microglobulin, neopterin and immunoglobulins rarely add information. Physicians and laboratories should have testing guidelines based on clinical audit of best practice, based in turn on scientific understanding of the immunological processes involved.

Acquired Immunodeficiency Syndrome↗

[Immunocorrectors in the complex treatment of postoperative suppurative-inflammatory complications in surgical patients and monitoring of immunological parameters].

The results of monitoring of immune parameters in different categories of surgical patients with postoperative purulent-inflammatory complications are described in the paper. The combined type of secondary immunodeficiency and degree second immunodeficiency according to A.M. Zemskov were detected in all patients. Immunocorrecting drugs, like polyoxidonium, imunofan and likopid, were added to the complex treatment of patients with the above complications. Their administration normalized the dynamic clinical course of the purulent-inflammatory processes and restored the immunological parameters.

Adjuvants, Immunologic↗

Interpreting cancer vaccine clinical trials.

A number of cancer vaccine strategies have entered initial Phase I clinical testing. In this review, Dr. Glenn Dranoff discusses the prospects that appropriate immunologic monitoring of patients in these trials can help delineate important differences among the various immunization strategies and prioritize the most promising approaches for further clinical development.

Antibodies, Neoplasm↗

Impaired anti-pneumococcal polysaccharide antibody production and invasive pneumococcal infection following heart transplantation.

An increased risk of invasive pneumococcal infection has been described among adult heart transplant (HT) recipients. Vaccination has been recommended before HT but the appropriate time for revaccination is not known. In a preliminary analysis of a prospective study involving a cohort of 32 HT recipients receiving daclizumab and triple immunosuppresion therapy, a progressive decline in pneumococcal polysaccharide antibody (anti-PPS) levels was observed during the first year after HT. One of the patients who was found to have a decrease in the levels of anti-PPS developed severe pneumococcal meningitis 20 months after HT. Before HT he had received non-conjugated 23-valent pneumococcal vaccine and showed a normal post-immunization anti-PPS production. The data suggest that long-term immunologic monitoring might be useful to recognize impairment of antibody responses under immunosuppressive therapy in HT.

Antibody Formation↗

Are surveillance endomyocardial biopsies necessary during OKT3 induction therapy?

BACKGROUND: To determine the utility of surveillance endomyocardial biopsies (EMBs) during a 14-day OKT3 induction course after cardiac transplantation, histologic results of the first two EMBs were retrospectively reviewed. METHODS: Seventy-three consecutive cardiac transplant recipients who received an OKT3-based quadruple sequential immunosuppressive protocol were analyzed. Patients were predominantly white (85%) and male (72%), with ischemic cardiomyopathy (54%) and a pretransplant panel-reactive antibody level of <10% (93%). RESULTS: The first EMB in 73 patients demonstrated no rejection in 70 patients (96%) and grade 1A rejection in 3 patients (4%). The second EMB showed no rejection in 64 patients (88%), grade 1A or 1B rejection in 8 patients (11%), and grade 3A rejection without hemodynamic compromise in only 1 patient (1%). Absolute CD3+ cells remained below 25 lymphocytes/mm3, and mean trough OKT3 serum levels exceeded 500 ng/ml throughout the 14 days of therapy, demonstrating the immunosuppressive efficacy of OKT3. Posttransplant echocardiograms showed normal left ventricular systolic function. CONCLUSIONS: Since 145 of 146 EMBs (99%) demonstrated no or minimal allograft rejection, a large cost savings could be realized if EMBs were performed only when clinically indicated during the 14-day OKT3 induction course in cardiac transplant recipients. Appropriate immunologic monitoring and echocardiographic testing may obviate the need for performing costly EMBs during OKT3 induction without an adverse clinical outcome.

Adolescent↗