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At least 19 recordsLinked to original sources
PubMed1979

Immunological monitoring as a guide to the management of transplant recipients.

Immunological monitoring assays are of current value in the management of transplant recipients. These assays allow the pre-transplant quantitation of both donor-recipient histocompatibility and recipient "responder status." In addition, these assays allow the individualization of immunosuppression, permitting a more uniform and effective immunosuppression in the difficult early post-transplant period. Individualized modulation of recipient immune reactivity avoids the documented pitfalls of conventional stereotyped suppression and permits better abrogation of acute rejection responses and lesser rates of serious infections consequent to excessive immune suppression. Immunological monitoring of long-surviving recipients permits early detection of immune reactivity which often culminates in clinical chronic rejection, as well as permits the quantitation of immune facilitory mechanisms (reduced capability to generate anti-donor cytotoxic T cells and/or cellular suppressor mechanisms) that indicate an immune milieu conductive to long-term graft survival. The primary limitations to the more widespread use of immunological monitoring assays at present are the need for more consensual validations of the utility of these assays in different laboratories, more standardization and better controls of techniques, and improvement in the technology of the assays to permit rapid, reproducible, and accurate results with a lesser expenditure of laboratory time and money and greater economy in demands for recipient blood and donor tissue. Finally, immunological monitoring assays are notable for the great promise they offer in terms of immunobiological probes to dissect mechanisms of rejection, mechanisms of graft facilitation, mechanisms of action of immunosuppressive agents, and mechanisms by which empirical technology of recipient pre-treatment may condition the host to better acceptance of an incompatible graft.

Animals↗
PubMed2004

Immunologic monitoring of maintenance therapy for acute lymphoblastic leukaemia in children-preliminary report.

BACKGROUND: In the study we evaluated immune reconstitution during maintenance therapy for acute lymphoblastic leukaemia (ALL) in relation to different treatment protocols and response of the immune system to the accompanying infections. PROCEDURE: The study group consisted of 40 children. The BFM protocol'90 was used in the standard risk group, while the New York protocol-in the high risk group. Assessment of the immune system was based on the analysis of peripheral blood mono-nuclear cells by flow cytometry and concentrations of immunoglobulins: G, M, A and IgE. Each patient was examined at 1-3 months' intervals. RESULTS: Following cessation of intensive therapy, the successive months of maintenance treatment showed: (1) a considerable depletion of B lymphocytes, a durable decrease in IgM, IgA and gradually increasing IgG; (2) a correlation between the time passing from the cessation of intensive therapy and increased numbers and percentage of B cells, and the helper/suppressor cell ratio. In the group of children treated according to the high risk protocol, compared to the low-risk group patients, we found lower levels of the following parameters: IgG, % lymphocytes: B and T lymphocytes (including CD4/CD8 ratio and "naive"/"memory" ratio) and NK cells (% and count). During infection: (1) a significant increase was noted in the percentage of T cells with HLA co-expression and monocytes with ICAM-1 co-expression, (2) the percentage of CD3(+)CD45RO(+) "memory" T cells was found to increase. CONCLUSIONS: Our findings indicate quantitative and qualitative changes of the immunity in children with ALL during maintenance therapy.

Adolescent↗
PubMed2003

Immunologic monitoring in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is characterized by progressive defects in humoral- and cell-mediated immunity. These defects are manifested as a propensity to develop infections with encapsulated bacteria, and less frequently, with gram-negative enterics. In addition, reactivation of viruses such as herpesvirus is not uncommon. Treatment of the disease further exacerbates immunosuppression by depleting immune effectors and broadening the spectrum of potentially offending pathogens. Risk of infection can potentially be reduced by administration of intravenous immunoglobulin and use of prophylactic antibiotics for individuals who are at high risk. Current work focuses on development of cellular and cytokine therapy to facilitate immune reconstitution in patients with CLL, thereby reducing morbidity and mortality and potentially improving survival.

Anti-Bacterial Agents↗
PubMed1991

Immunological monitoring in cyclosporine-treated patients.

The immunosuppressive action of cyclosporine (CsA) in vivo is thought to primarily involve its inhibitory effect on lymphokine production by T lymphocytes. Most efforts to assess immunosuppression in CsA-treated patients have concentrated on measuring some aspect of activated T cell function. These have included monitoring of lymphocyte subsets and the appearance of activated T cell markers, assaying the production of lymphokines and the direct measurement of lymphokines in serum and urine, and most recently measurement of soluble interleukin-2 receptor (SIL2R). Using a new microparticle enzyme immunoassay (MEIA) in a preliminary study of 12 CsA-treated renal transplant recipients, we found significant increases in serum SIL2R levels in patients with rejection and we conclude that MEIA may have some use in the monitoring of CsA-treated patients.

Cyclosporins↗
PubMed2004

Immunological monitoring of posttransplant allograft sensitization following living related donor renal transplantation.

A better understanding of the immunobiological processes and predictors of graft rejection holds promise for development of new therapeutic strategies and also for individualization of immunosuppression. The objective of this study was to analyze the clinical relevance of immune parameters, such as recipient sensitization status, donor-specific antibodies, and anti-HLA antibodies, which are major predictors of graft outcome following renal transplantation. Sera from 264 renal recipients at different posttransplant period were included for detection of anti-donor antibodies (by flowcytometry); anti-HLA, antibody (by ELISA), and panel-reactive antibodies (PRA) by complement-dependent cytotoxicity (CDC) methods. Graft survival was analyzed in relation to posttransplant PRA at 2 years follow-up time: overall survival was significantly compromised in the highly sensitized group (group III) compared to the other two groups (overall chi2 = 24.20, P = 5.5 x 10(-06)). Flow cytometric cross-matches revealed the presence of anti-donor class I antibodies (T+) in 39 patients who had a poor graft survival of 51% compared with 85% survival in 225 antibody-negative patients. (chi2 = 22.260, P = 2.381 x 10(-.06)). Further analysis was performed based on the presence or absence of FCXM and ELISA-detected antibodies. Recipients belonging to group I (ELISA+/FCXM+) showed significantly lower graft survival (43%) compared with that observed in group II, which were essentially nonsensitized individuals (90%; P = 3.1 x 10(-08)). The graft survival in the ELISA-/FCXM+ group was 63%, which was significantly lower than that in group II (P = 5.14 x 10(-03)). Group IV (ELISA+/FCXM-) including 38 (14%) serum samples with nondonor but HLA-specific antibodies was associated with significantly poorer graft survival (63%) compared with group II (P = 6.6 x 10(-05)). Our data also show that while FCXM is the most sensitive test to detect donor-specific antibodies, the ELISA method offers the additional advantage of detecting anti-HLA class-I antibodies, which are detrimental for renal graft survival. Thus the use of multiple parameters to assess recipient immune profile can predict graft outcome more accurately thus helping the individualization and optimization of immunosuppression.

Follow-Up Studies↗
PubMed1994

Current status of immunological monitoring in the renal allograft recipient.

With the appropriate combined use of different immune monitoring techniques, it is possible to derive sensitive diagnostic parameters for the transplant surgeon. However, the core biopsy or cytological examination of the graft continues to represent the gold standard for evaluating the specificity and sensitivity of these methods. With the development of newer monoclonal antibodies and a better understanding of the impact of immune processes on the behavior of various activation linked, T cell associated surface antigens, one may be able to secure further valuable information, with enhanced diagnostic and prognostic accuracy.

ABO Blood-Group System↗
PubMed2002

Immunological monitoring during therapeutic vaccination as a prerequisite for the design of new effective therapies: induction of a vaccine-specific CD4+ T-cell proliferative response in chronic hepatitis B carriers.

We characterized the anti-viral T-cell response in 22 chronically infected patients, who participated in a European multi-center randomized placebo-controlled, double-blind study therapeutic vaccination trial with pre-S1, pre-S2 and S antigenic components of the hepatitis B virus (HBV). It induced a significant HBsAg-specific T-cell proliferation and the production of Th2-cytokines (i.e. IL-5). A specific induction of Th1-lymphokines was not detectable although this has been demonstrated in this study in response to the nucleocapsid protein (HBcAg). Further analysis indicated that this approach does not activate HBV-specific CD8+ T-lymphocytes as detected by ELISPOT-assay. Our results might explain why a specific therapeutic vaccine, although safe and well-tolerated is not always able to break tolerance leading to the clearance of the hepatitis B virus.

Adult↗
PubMedDate not supplied

Comparative evaluation of 'TaqMan' RT-PCR and RT-PCR ELISA for immunological monitoring of renal transplant recipients.

By sequentially monitoring cytokine gene expression (using RT-PCR ELISA technology) in peripheral blood cells of renal transplant recipients in the early post-operatively period we have shown that expression patterns correlate with clinical events, namely acute allograft rejection. This strategy may have the potential of predicting acute rejection prior to clinical detection. Unfortunately, the technique used was time consuming and only semi-quantitative and, therefore, not suitable for clinical application. In this study, we have sought to confirm the results of the early work using a real time quantitative RT-PCR technique ('TaqMan'), which may be applicable in the clinical laboratory. 'TaqMan' primers and probes were designed for Interleukin (IL)-4 and IL-10 using Primer Express software. Cytokine gene expression for both cytokines was re-measured in stored cDNA samples from 27 non-rejectors and 14 patients experiencing an episode of biopsy proven acute rejection. Compared to pre-transplant levels, IL-4 gene expression fell significantly on post-operative days 2 and 7 before returning to baseline values by day 14 in the non-rejectors. In the rejectors, the initial significant fall was again seen, but with an earlier return to pre-transplant levels at the time of rejection diagnosis. This was followed by a further significant fall in levels 48 h after the initiation of anti-rejection therapy. These different patterns for rejectors and non-rejectors were seen using both techniques. For IL-10, gene expression increased significantly following transplantation throughout the study period when compared to baseline values. This pattern was seen using both techniques. In the rejectors, there were different patterns seen depending on the technique used. When using RT-PCR ELISA, the initial rise was again seen followed by a return to baseline values at the time of rejection diagnosis followed by a further significant rise in gene expression after the start of anti-rejection treatment. The pattern resembled those of the non-rejectors when expression was measured using 'TaqMan'. This study has confirmed that sequential monitoring of cytokine gene expression, measured in peripheral blood mononuclear cells, detects significant changes that correlate with clinical events in renal transplant recipients, including acute rejection, although not all changes detected with RT-PCR ELISA were confirmed. Therefore, real time quantitative RT-PCR technology may be useful in monitoring the immunological status of these patients in the early post-operative period.

Enzyme-Linked Immunosorbent Assay↗
PubMedDate not supplied

Immunologic monitoring of cancer vaccine therapy: results of a workshop sponsored by the Society for Biological Therapy.

The Society for Biological Therapy held a Workshop last fall devoted to immune monitoring for cancer immunotherapy trials. Participants included members of the academic and pharmaceutical communities as well as the National Cancer Institute and the Food and Drug Administration. Discussion focused on the relative merits and appropriate use of various immune monitoring tools. Six breakout groups dealt with assays of T-cell function, serologic and proliferation assays to assess B cell and T helper cell activity, and enzyme-linked immunospot assay, tetramer, cytokine flow cytometry, and reverse transcription polymerase chain reaction assays of T-cell immunity. General conclusions included: (1) future vaccine studies should be designed to determine whether T-cell dysfunction (tumor-specific and nonspecific) correlated with clinical outcome; (2) tetramer-based assays yield quantitative but not functional data (3) enzyme-linked immunospot assays have the lowest limit of detection (4) cytokine flow cytometry have a higher limit of detection than enzyme-linked immunospot assay, but offer the advantages of speed and the ability to identify subsets of reactive cells; (5) antibody tests are simple and accurate and should be incorporated to a greater extent in monitoring plans; (6) proliferation assays are imprecise and should not be emphasized in future studies; (7) the reverse transcription polymerase chain reaction assay is a promising research approach that is not ready for widespread application; and (8)there is a critical need to validate these assays as surrogates for vaccine potency and clinical effect. Current data and opinion support the use of a functional assay like the enzyme-linked immunospot assay or cytokine flow cytometry in combination with a quantitative assay like tetramers for immune monitoring. At present, assays appear to be most useful as measures of vaccine potency. Careful immune monitoring in association with larger scale clinical trials ultimately may enable the correlation of monitoring results with clinical benefit.

Animals↗
PubMed1978

Immunologic monitoring of transplant rejection: correlation of in vitro assays with morphologic changes on transplant biopsy.

The assays of lymphocyte-mediated cytotoxicity (LMC), antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) were correlated with histopathologic criteria of refection in 35 transplant biopsies. A positive LMC was seen with 6/8 biopsies showing moderate to severe cellular rejection and in 8/17 with mild cellular rejection. Positive ADCC and/or CDC assays were associated with 14/14 biopsies containing rejection vasculitis. These results suggest that selected in vitro assays may be useful in monitoring the immunologic events occurring in the rejecting allograft.

Antibody-Dependent Cell Cytotoxicity↗
PubMed2004

[Immunologic monitoring in children with acute lymphoblastic leukemia during maintenance treatment with regard to co-existing infections].

UNLABELLED: We analyzed the dynamics of changes in the immune system during maintenance treatment of acute lymphoblastic leukemia (ALL). The study was carried out on the group of 40 children aged 2-15 years (mean +/- 3.46), including 31 lower risk patients (Berlin-Frankfurt-Munich protocol--BFM) and 9 high risk patients (New York protocol--NY). Levels of IgA, IgG, IgM and IgE, and subsets of mononuclear cells using flow cytometry were evaluated in the study group every 1-3 months. During maintenance therapy we found markedly reduced leukocytosis, lymphocytosis, and mean values of IgA, IgM and IgG in comparison to healthy children. A gradual increase was observed in the level of IgG, in the percentage and absolute number of B lymphocytes (CD19+) and in helper/suppressor T-cell ratios. In the group of patients treated according to the NY protocol, a decrease was noted in: lymphocytosis, in the percentage of lymphocytes B, in the levels of IgG and IgM, in the percentage and absolute numbers of T lymphocytes, T-helper cells and CD4/CD8 and CD3 RA/RO ratios, compared to standard risk patients. In the course of infection, a transitory increase was observed in activated T-cells, and a rise was found in the number of T-memory cells and monocytes showing the expression of adhesive molecules. CONCLUSIONS: In the course of maintenance treatment in children with ALL, constant suppression of the immune system, of both humoral and cellular responses, can be observed especially in the group of children treated according to the NY protocol; activation of T lymphocytes and monocytes takes place in the course of infection. Lack of this activation may be a marker of poor prognosis during the infection.

Adolescent↗