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PubMed1984

[Importance and limitations of the immunological monitoring of patients with malignant tumors].

The authors, after considering the incidence of neoplastic diseases is particularly high in subjects suffering from congenital or acquired immunologic lacks, assert the importance to perform an immunologic monitoring in the patients bearing malignant neoplasms, with the purpose to identify and calculate the direrent deficits of the sheltering organism. Then, they state the method adopted for the study of the cellulo-mediate immunity (in vivo and in vitro) and the humoral one. At last, on the basis of the results they obtained, the Authors, as a conclusion, affirm there is always in neoplastic patients a certain degree of depression of tumour immunity (especially if cellulo-mediate), and it can be put in relation to the evolutive stage of neoplasm.

Adult↗
PubMed1979

[Immunological monitoring of patients with carcinoma of the lung. Study method and preliminary research].

It is by now an established fact that the status of the immune system stands in some relationship with the onset and evolution of malignancy. To clarify this relationship the authors investigated the immune system of patients with pulmonary carcinoma, with special regard to the functions of the T and B lymphocyte lines. After suitable explanation of their experimental protocol, which involved immunological monitoring and the study of relationships between immunological changes and the extent and histological type of malignancy, and also the effects of any treatments being administered, the authors describe the results obtained in 18 preoperative patients. The study revealed an overall diminution of cell-mediated immune activity: less strongly positive DNCB skin tests, reduced capacity for making E rosettes, reduced blast transformation with PHA. With B lymphocytes the EA rosette test was often depressed, whereas antibody titers were normal or even above normal, and the pokeweed blast test was invariable above normal values. These preliminary results show that at the time of diagnosing malignancy, the greater aggressiveness characteristic of the less differentiated cellular types, or of stages of diffuse malignancy, is associated with overpowering of cell defenses and (within certain limits) enhancement of the humoral response.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2004

Immunological monitoring of cancer vaccine therapy.

Immunological treatment of malignant diseases in humans aiming at the induction and proliferation of antigen-specific T cells has made rapid progress in recent years. A growing number of tumour-associated antigens, potentially synergistic combinations with adjuvants, and various routes of application provide new opportunities for cancer vaccination. Therefore, a highly accurate assessment of vaccine-induced T cell responses is required. Three T cell assays (tetramers, intracellular cytokine flow cytometry and ELISPOT assay) have emerged as first-line methods for monitoring T cell induction during vaccination. These assays are relatively easy to perform, reliable, sensitive and allow an ex vivo T cell analysis at the single cell level. Although at this stage assays are not a defined surrogate marker for clinical efficacy, they already provide information concerning the immunological potency of a given vaccine. In particular, comparing immune responses under various treatment conditions will help to develop more clinically efficient tumour vaccination. Novel assays, such as CD107 staining, human leukocyte antigen/green fluorescent protein-antigen-presenting cells or microarrays, and assays determining functions, such as proliferation assays, are beginning to complement first-line monitoring assays.

Antigen-Antibody Reactions↗
PubMed1985

Immunological monitoring of plasma exchange in primary IgA nephropathy.

Plasma exchange (PE) has recently been proposed for primary immunoglobulin (Ig)-A nephropathy (PIgAGN) with progressive course. To develop suitable guidelines for PE in these cases, the authors evaluated the clinical usefulness of some immunological parameters in five patients with PIgAGN treated with PE combined with immunosuppressive drugs and small doses of corticosteroids. These parameters included the levels of IgA-containing immune complexes (IgAIC) by a specific conglutinin assay, the function of the mononuclear phagocyte system (MPS) by the in vivo clearance of IgG-sensitized erythrocytes, and complement activation as determined by C3d measurement. HLA types were also determined. Three patients had an acute nephritic syndrome with a rapidly progressive course, one of them showing sclerotic histologic changes. The two other cases had a relentless progression toward renal failure. In the patient with sclerotic PIgAGN, the MPS function was normal and the IgAIC and C3d levels were low throughout the treatment. In the other four cases, the high IgAIC and C3d levels and the MPS dysfunction found before treatment markedly improved after several PEs. The immunological parameters remained normal during the post-PE follow-up in two cases with acute nephritic syndrome and rapidly progressive course, but worsened again in two cases with a relentless course, particularly in one who possessed the B8/DR3 HLA type. Immunological monitoring including IgAIC, C3d, and MPS function is proposed, in addition to histological and clinical evaluation, as a guideline for PE in PIgAGN with evolving course.

Adolescent↗
PubMed1986

Infusion of autologous alloactivated lymphocytes in melanoma patients: toxicity and immunologic monitoring.

Previous work has shown that infusion of autologous helper-enriched, alloactivated lymphocytes in melanoma patients may induce, in addition to other mild signs of toxicity, a transient but sharp elevation of blood pressure. To avoid such a disturbing symptom, the in vitro protocol of peripheral blood lymphocyte activation has been modified. In the present study we show that such a modification has led to a lower toxicity of autologous lymphocyte infusion in 4 melanoma patients; in particular, hypertension was no longer observed. In addition, an immunologic monitoring was carried out in these patients. In 1 of 4 patients the treatment enhanced the in vitro cytotoxic activity of peripheral blood lymphocytes against autologous tumor cells. Other parameters such as NK activity and T4/T8 ratio did not show significant trends. The possible implications of these findings for clinical trials of adoptive immunotherapy with lymphocytes are discussed.

Adolescent↗
PubMed1983

Immunological monitoring of diabetic and nondiabetic recipients of renal allografts.

Peripheral blood T-lymphocyte populations were monitored sequentially in diabetic recipients of renal allografts. Unfractionated buffy coat preparations were reacted with the murine monoclonal antibodies, OKT3 (all circulating T-cells), OKT4 (helper/inducer/regulatory T-cells), and OKT8 (cytotoxic/suppressor cells). Levels of peripheral blood lymphocyte subpopulations of diabetic patients monitored prior to transplantation revealed no significant abnormalities. Following transplantation, but prior to any therapy for acute rejection, the mean percentage of OKT3, 4, and 8 reactive cells in diabetic recipients closely resembled those observed in nondiabetic recipients. After treatment for acute rejection, a marked decrease in the mean OKT4/OKT8 ratio from normal (1.90 +/- 0.7) was observed in both diabetic (1.04 +/- 0.5), and nondiabetic (1.35 +/- 0.5) allograft recipients. Eleven of thirteen diabetic recipients with long-term functioning allografts were found to have a depressed OKT4/OKT8 ratio (mean 1.03 +/- 0.6). T-cell subset monitoring of diabetics with end-stage renal failure failed to reveal any significant differences from nondiabetic, uremic patients. The high incidence (75%) of allograft rejection noted in these diabetic allograft recipients similarly suggests normal immunocompetence. Following successful completion of rejection therapy, however, reduction in the ratio of OKT4 to OKT8 reactive cells suggests that an alteration in immune responsiveness has occurred. Immunological monitoring of these long-term diabetic recipients with functioning allografts suggests that the observation of a consistently depressed OKT4/OKT8 ratio may (1) be useful in predicting continued allograft function and (2) prompt the more rapid reduction of steroid medication to maintenance dosage since this pattern may be indicative of subclinical viral infection.

Adult↗
PubMed1977

Immunological monitoring of long-surviving renal transplant recipients.

In this study a variety of cell-mediated immunity responses were performed in long-term (2 to 12 year) human leukocyte antigen-A (HLA) nonidentical renal transplant patients. All patients showed mixed lymphocyte culture (MLC) stimulation against donor, indicating a lack of tolerance. Of successful long-term transplant patients, 73 percent showed high serum levels of MLC-blocking activity. A consistent association of successful long-term transplantation and a specific defect in recipient ability to generate cytotoxic cells against donor was seen at the 8 to 12 year level. A close association of lymphocyte-dependent activity (LDA) and clinical chronic rejection was found, and LDA could be identified prior to the onset of clinical chronic rejection in most cases. Four patients had a positive LDA assay prior to transplant and all four went on to develop chronic rejection. Recipients taking immunosuppressive drugs within 24 hours of testing had a deficient capability to generate cytotoxic effector cells against indifferent individuals. These findings demonstrate a consistent association of in vitro cell-mediated immunity parameters and in vivo transplant function and may represent a valuable immunological monitoring system for long-term recipient follow-up.

Antibodies↗
PubMedDate not supplied

Immunologic monitoring with Orthoclone OKT3 therapy.

Muromonab-CD3 monoclonal antibody (Orthoclone OKT3) was used 146 times in 123 transplant recipients to treat or prevent rejection. Reversal and prevention of rejection were evaluated 1 week and 1 year after OKT3 therapy. Eighty-one percent (73 of 90) of the rejection episodes in kidney transplant patients were reversed with 67% of these grafts functioning at 1 year. Eighteen of 20 (90%) rejection episodes in liver transplant recipients were reversed, as were 11 of 13 (85%) heart transplant rejection episodes. Only one of five pancreas transplant episodes were reversed. OKT3 was used prophylactically in 18 transplant recipients (13 kidney, four heart, one liver). Immunologic monitoring (lymphocyte subsets, serum OKT3 levels, and antimurine antibodies) was performed during and after OKT3 therapy. Antimurine antibody formation rate was 28% (26 of 94 patients monitored). OKT3 therapy resulted in a rapid depletion of CD3+ cells from the peripheral circulation (less than 20/mm3) and trough serum OKT3 levels of greater than 800 ng/ml by the third day of therapy in all transplant types. Twenty-three patients (14 kidney, five liver, three heart, and one pancreas) were retreated with OKT3; reversal of rejection occurred in 87% of patients (13 of 15) with no antimurine antibodies and in 83% of patients (five of six) with a low antibody titer but did not occur in the two patients with a high antibody titer. Retreatment of patients with no anti-OKT3 antibody resulted in a depletion of CD3+ cells from the peripheral blood, but it took longer than in patients treated with OKT3 for the first time. Similarly, serum OKT3 levels increased slower in retreated patients compared with first treatment. In retreatment patients with a low titer antimurine antibody, often it was necessary to increase the dose of OKT3 to achieve adequate serum OKT3 levels and to deplete CD3+ cells. Antimurine antibody developed de novo in four of the 15 antibody negative patients (27%) who were retreated. Overall, OKT3 was an effective agent in reversing and preventing rejection in solid organ transplantation with few severe side effects and a low mortality. Retreatment with OKT3 should not be considered unless the antibody status of the patient is known. Development of low titer antibodies does not preclude successful retreatment with OKT3. Alternate antirejection therapy, however, should be used in patients with high titer antimurine responses.

Antibodies, Anti-Idiotypic↗
PubMed1996

[An attempt of immunological monitoring of patients with laryngeal carcinoma by flow cytometry].

In a group of 60 patients with surgically treated laryngeal carcinoma blood lymphocyte subsets were assessed on the day of surgery (day 0) and six weeks thereafter by means of flow cytometry. Blood cells at day 0 were also compared to tumor infiltrating lymphocytes (TIL) isolated from surgical specimens. Significant alterations were found in postoperative period as compared to day 0 manifested by the fall of B cells, increase of activated T lymphocytes and NK cells. There were also marked changes between blood cells at day 0 and TIL, evidence in rise of B cells, of activated T lymphocytes and decline of NK cells within the latter. These data suggest that the assessment of lymphocyte subsets may be of value in immunological monitoring of laryngeal carcinoma patients.

B-Lymphocytes↗
PubMed1997

Cultures of aspiration biopsy specimens in the immunological monitoring of renal transplants.

OBJECTIVE: Graft-infiltrating cells (GIC) have been studied in heart, lung, and liver transplants and have been shown to have greater proliferative ability when taken from rejecting allografts. Our aim was to study GIC harvested by fine-needle aspiration biopsy (FNAB) in renal transplant recipients. PATIENTS AND METHODS: 93 adult patients entered the study. The FNABs were done on the 7th, 14th, and 30th day after transplantation in stable cases and whenever a rejection crisis supervened. RESULTS: The proliferation responses of GIC were significantly higher in rejection than in stable cases during the 1st month after transplantation. The sensitivity for rejection was 96.4%, the specificity 91.3%, the negative predictive value 98.7%, and the positive predictive value was 93.3% among dysfunctioning grafts. CONCLUSIONS: The study of the proliferative capacity of graft-infiltrating cells in renal transplants is a safe and very useful immunologic monitoring tool, and it could improve the FNAB diagnostic accuracy.

Adolescent↗
PubMed2000

American Association for Cancer Research: Clinical trials of immunotherapeutics and immunologic monitoring. April 1-5, 2000, San Francisco, CA, USA.

A major session at this annual gathering of the cancer researchers from around the globe dealt with the current state of immunotherapy for cancer. Immunotherapy is a form of cancer treatment that enhances its scientific promise and legitimacy with each passing year. As a result, this topic has become one of the most highly attended and anticipated of all the sessions during the AACR. This year's session included further progress from the laboratory to the clinic involving an ever-increasing number of cancers. For example, brain, lung and prostate cancer are now as well-represented as melanoma and lymphoma at such forums. This year's session continued the trend of impressive biosafety of both cell- and antibody-based vaccines. Therefore, these cancer vaccines offer optimism in treatment benefit as well as a minimal impact on quality of life. Lastly, the increasing number of clinical responses allows for true immunological monitoring, as scientists strive to unlock the mysteries behind what makes one patient respond to treatment and another progress. Several groups discussed in vitro immune parameters that were studied in concert with their clinical trials. Others discussed ways in which those in the immunotherapy community can work towards more reliable immune monitoring and ultimately a surrogate marker for response.

Immunotherapy↗
PubMed1997

[Immunological monitoring of patients with disseminated colorectal cancer under thermochemotherapy].

The basic immunological indexes were investigated in patients with disseminated colorectal cancer after conduction of magnetothermia and chemotherapy using fluorouracil. Control group consisted of 11 patients, to whom monotherapy with fluorouracil was prescribed. The modifying action of magnetothermia alleviates significantly the immunodepressive effect of cytostatic drugs.

Antimetabolites, Antineoplastic↗
PubMed1995

Immunologic monitoring of OKT3 induction therapy in cardiac allograft recipients.

OKT3 induction therapy was monitored in 31 cardiac allograft recipients during the 1st year posttransplant. Serum level of OKT3, anti-OKT3 antibodies, and interleukin-2 (IL-2) were monitored during the first 2 months posttransplant. These values were retrospectively correlated with allograft rejection episodes which occurred during the 1st year posttransplant and allograft survival rates over a 3-year observation period. We found that OKT3 induction therapy (10-14 days) was not associated with the development of anti-OKT3 antibodies manifest by dropping OKT3 levels during OKT3 therapy, and is not associated with the development of vascular rejection in our patient population. Patients with high titer ant-OKT3 antibodies, erratic serum OKT3 levels, and/or high serum IL-2 levels (> or = 5 ng/ml) during the first 2 months posttransplant showed a higher incidence of allograft rejection (predominantly cellular rejection) during the 1st year posttransplant and showed lower allograft survival rates. We also showed that a concomitant elevation of serum IL-2 levels was found in patients who developed anti-OKT3 antibodies. CD3+ T-cell levels were not predictive of inefficacy of OKT3 therapy. We conclude that immunologic monitoring of serum OKT3, anti-OKT3 antibody, and possibly serum IL-2 levels is critical for identification of patients who develop early, OKT3-resistant rejection episodes and for the identification of patients who may be more susceptible to allograft rejection and decreased allograft survival long after completion of OKT3 therapy.

Antibodies, Anti-Idiotypic↗
PubMed2000

The use and misuse of immunologic monitoring after transplantation: approaches that have proved useful.

Current practice in the monitoring of cardiac transplants revolves around the use of the endomyocardial biopsy. While this is effective for the identification of an ongoing immune response in the graft, for years investigators have explored less invasive approaches in the hope of achieving the same goal by examining the patient's immune response. For a number of years, lymphocytes, their subsets, and their level of activation in the periphery were investigated. To a large degree, it was a lack of specificity in these approaches that led to their falling out of favor. Examination of donor-specific reactivity by means of lymphocyte proliferation assays has also been used; however, these approaches have been impeded by the time and effort required to accomplish them. During the last few years, flow cytometric cross-matching during the posttransplant period has been used at our institution. While this cross-matching focuses on the humoral immune responses, we have found it to be of value in identifying patients at risk of rejection and in allowing the assessment of treatment modalities used to treat ongoing rejection. While the perfect approach remains to be found, the potential advantages of immunologic monitoring would seem to justify continued study.

Antibody Formation↗
PubMed2001

[Technological advances in immuno-oncology: from fundamental concepts to patient immunological monitoring].

Over the past decade, cancer immunology has known several advances due to both basic research and new technologies recently developed in this field. This review will illustrate the impact of some new immunological technologies and how the latter resulted in the exploration of new territories in cancer immunology and the emergence of new concepts that allowed to revisit the immunosurveillance concept and permitted to improve the patient monitoring.

Antigens, Neoplasm↗
PubMed1997

Immunological monitoring of dry-cleaning shop workers--exposure to tetrachloroethylene.

A panel of immunological parameters has been examined in a group of dry-cleaning workers (n = 21) and in a control group of administrators (n = 16) from the same plant. The results were also compared to long-term laboratory reference values (LRV) (n = 14-311). External exposure to tetrachloroethylene (PER) was represented by TWA (8 h) values in the range 11-752 mg PER/m3. Biological monitoring showed an amount from 9 to 344 mg PER/m3 in exhaled air by the end of workshift. 1. The exposed dry-cleaning workers compared to the controls from the plant had statistically significant changes in metabolic activity of phagocytes, alpha 2-macroglobulin, C3 and C4 complement component, salivary secretory IgA, and blastic transformation test. Most of the values were within the range of normal values. 2. The exposed dry-cleaning workers had several abnormal immune parameters compared to the long-term laboratory values (LRV) especially in the alpha 2-macroglobulin, C3 and percentage of T-lymphocytes. Most of the changes, even those that were statistically significant, were still within the range of normal values, but they might be classified as trends or shifts away from normal (spontaneous blastic transformation, absolute number of phagocyting cells, coeruloplasmin, circulating immunocomplexes, serum lysozyme). 3. The non-exposed controls from the same plant showed both quantitative and qualitative differences when compared to the LRV. Changes were seen in IgG, C4, CSI and in increased spontaneous metabolic activity of leucocytes, total leucocyte count, absolute number of phagocyting cells, alpha 2-macroglobulin, prealbumin, C4, circulating immunocomplexes and serum lysozyme. 4. The distribution analysis of all results detected a large number of abnormal values in both groups, more in the at-risk group. 5. As inhalation was the main route of PER exposure it was concluded that the changes might represent aspects of the response of the respiratory immune system, mainly of the alveolar macrophages. Additional postinfection effects could not be excluded in both studied groups. Individual differences in immune reactivity as well as individual range of exposure should be taken into consideration.

Adult↗
PubMed1993

[Immunologic monitoring after severe trauma].

Trauma, burn injury, and major surgery lead to severe suppression of the immune system with an increased susceptibility to septic complications. Therefore, the monitoring of essential immune functions in the early and late post-traumatic course may permit trauma patients with an increased risk for infectious complications to be identified. Most functions of the specific and non-specific immune system can be determined with ELISA, RIA, or other immunological techniques. However, only a small number of these techniques demonstrate an acceptable sensitivity and specificity for infectious complications. Moreover, the techniques used in daily monitoring should be simple, reproducible and not expensive with regard to materials. For immunological monitoring we suggest two scoring systems (ISS; APACHE II), biochemical parameters (elastase, neopterin, CRP, lactate), and interleukin-6 plasma levels. The clinical relevance of this monitoring must be proven in clinical studies.

Burns↗