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Results for “Monitoring, Immunologic”

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PubMed1989

[Use of antilymphocytic gamma globulin to monitor the course of viral hepatitis B].

The authors suggest a method for immunologic monitoring of the lymphocytic activity in viral hepatitis B (VHB) by the antilymphocytic gammaglobulin (ALG) capacity to inhibit rosette formation with sheep red blood cells. The findings evidence that sensitivity to ALG augments in the majority of VHB patients, this manifesting as an increased titre of this globulin inhibiting activity in the E-rosette formation test. A decreased sensitivity of the lymphocytes to the effects of specific antibodies points to activation of T lymphocytes and is regarded as an unfavourable prognostic sign.

Adult↗

PubMed2006

CD4(+) memory T cells with high CD26 surface expression are enriched for Th1 markers and correlate with clinical severity of multiple sclerosis.

An aberrant immune activation is believed to be important in the pathogenesis of multiple sclerosis (MS). Expression of CD4(+) T lymphocyte surface molecules indicative of immune activation and effector functions has been correlated with disease severity and activity. CD4(+) CD45R0(+) CD26(high) memory T lymphocytes contained the high levels of markers of Th1, activation, and effector functions and cell counts of this subset correlated with MS disease severity. This subset had lower expression of PD-1, CCR4, and L-selectin in MS than in controls. These changes were only partially normalised by treatment with interferon-beta. We point to this subset as a putative target for immunological monitoring of MS disease activity and of treatment efficacy.

Adult↗

PubMed1993

Clinical immunology and HIV infection.

Clinical immunologists play a major role in the multidisciplinary approach to the management of human immunodeficiency virus (HIV) infection and its complications in Australia, through involvement with the clinical and laboratory management of patients as well as with research on disease pathogenic mechanisms. Consequently, immunological monitoring of the pathogenic effects of chronic HIV infection is commonplace, allowing for studies on the clinical utility of immunological investigations as a means of monitoring the severity of HIV-induced immunopathology and immunodeficiency to be undertaken. Such studies have demonstrated the clinical utility of CD4+ T-cell assays, but studies on cutaneous delayed-type hypersensitivity have demonstrated that the cellular immunodeficiency induced by chronic HIV infection may be more complex than CD4+ T-cell depletion alone. In addition, the involvement of clinical immunologists has greatly facilitated studies on the pathogenic mechanisms underlying HIV-induced immunopathology. Such activities place Australia in a very advantageous position for future studies on the use of immune-based therapies for controlling the pathogenic effects of chronic HIV infection.

HIV Infections↗

PubMedDate not supplied

Prospects and limitations of systematic monitoring in patients with laryngeal cancer.

The authors report the first results concerning the systematic use of "immunological monitoring" in patients suffering from well-developed laryngeal cancer. The authors have also studied, in 50 cases in different stages of development, the activity of T-cells using the cutaneous tests (BCG, PPD, PHA and SK-SD), the E-rosette test and the PHA-induced lymphocytic blastization test (it is well known that the T-cells are responsible for a cytotoxic effect against neoplastic cells). The authors have also studied the activity of B-lymphocytes by means of the EA and EAC rosette test and of IgG, IgA, IgM and complement serum titles. They have observed a progressive depression of the T-cell activity after surgical intervention, whereas the B-cell activity in several cases tends to increase. The authors discuss these immunological results and the possibility that these findings may represent the basis for a complementary immunotherapy following the surgical treatment and/or radiotherapy or chemotherapy. Finally, the authors discuss the possibilities and the limitations of these immunological methods from the point of view of clinical application.

B-Lymphocytes↗

PubMed2006

Laboratory analysis of T-cell immunity.

Immune-based strategies for treating and preventing cancer are increasingly being tested and include cancer vaccination, adoptive T cell therapy, and cytokine therapy. An important component of testing and development of immune-based strategies is monitoring the immunologic response. The ability to monitor T cell immunity has been suboptimal. The measurement of tumor-specific immunity will aid in defining which strategies should be moved forward in clinical trials and which should be eliminated or evaluated further in the preclinical realm. Immunologic monitoring is necessary for determining if an approach has immunologic efficacy and ultimately whether immunologic responses correlate with a clinical response. This article discusses several important elements of measuring T cell immunity such as validation principles, laboratory issues, current approaches, and new paradigms and concepts for future testing. Informative immunologic monitoring of T cells will be one of the driving forces in advancing the field of tumor immunology.

CD4-Positive T-Lymphocytes↗

PubMed1981

Serial study of circulating immune complexes before and after renal transplantation.

To clarify the relationship of circulating immune complexes (CIC) to acute rejection or intercurrent infection, we studied the presence of CIC's by four methods in renal allograft recipients, by serial monitoring, before and after transplantation, of both CIC and donor-specific immunologic parameters. Three of the methods were dependent on the precipitation of CIC with low concentrations of polyethylene glycol (PEG). They were the radioisotopic conglutinin-binding assay, the Clq-binding assay, and the radial immunodiffusion (RID) of IgG and IgM in PEG precipitates. The fourth method was the Raji cell assay. These techniques were applied to sequentially collected serum samples from 26 patients, both before and up to 20 months after transplantation (mean followup, 7.2 months). CIC's were present in 14 out of 26 (54%) patients studied before transplantation. Glomerulonephritis was the primary renal disease in only half of these patients. Of this half, 12 (86%) were positive after transplantation, whereas only 2 of the 12 (17%) with no CIC before transplantation became positive subsequently. CIC's were demonstrable in 19 out of 28 patients (68%) during the posttransplant observation. In five instances (4 patients), they appeared only transiently (in 1 in association with rejection and in another 2 with intercurrent infection). In 14 patients, CIC's were detectable until the end of the observation period. In 23 rejection episodes in 16 renal allograft recipients, CIC's were present in association with 9 (39%) of these episodes, but the appearance or reappearance of CIC's coincided with rejection in only 5 of these episodes (or 22%). Thus, a cause-and-effect relationship is not established. In contrast, test for donor-specific immunologic monitoring, especially lymphocyte-mediated cytoxicity (LMC-D), became positive for 63% of the rejections and became negative when rejection activity subsided. CIC's were present at the time of only 4 of 15 infective episodes (27%). The fate of the allograft was no different in the CIC-positive group compared with those in whom they could not be detected. Among another 33 patients with long-surviving grafts (mean, 3.7 years) and studied for brief periods, CIC's were detected in 6 (18%). All 6 had excellent graft function though 1 had developed membranous glomerulonephritis.

Antigen-Antibody Complex↗

PubMed2003

[The role of immunopathological reactions in the development of eye diseases in persons infected by hepatitis B virus and the efficiency of immuno-correcting therapy].

The role of immunologic factors in the development of ophthalmic pathologies in persons infected by hepatitis B virus (HBV) affecting the liver or in asymptomatic virus carriers (a total of 285 persons, 328 eyes) was studied. The deficit of CD3 and CD4 cells, gammopathy, increased levels of circulating immune complexes and of TNF-alpha in the serum; the deficit of IgA and an enhanced secretion of IgG in the lachrymal fluid; as well as a weakened ability of the local and systematic production of IFN-alpha were typical for a majority of patients. The most profound changes were detected in cases of uveitis; apart from the above mentioned, an increase of the CD4/CD8 index as well as of organ-specific and inter-organ immunization was found. The cases of keratitis (92% of the stromal type) were distinguished through a hypersecretion of TNF-alpha both in the serum and in the lachrymal fluid. Complicated cataracts were observed mainly in convalescents or in asymptomatic virus carriers; immune disorders were less seldom encountered in this category, as compared to the cases of eye inflammations, and basically they were local. The obtained data were considered in treatment. Imunofan, when added to the traditional therapy (symptomatic and corticosteroid one), activated the local and systematic antiviral immunity, suppressed the production of pro-viral cytokines and reduced the autoimmune reactions. As a result of this, the treatment time, the frequency rate of relapses as well as the number of anti-inflammatory and postoperative (in cataracts) complications decreased. The study results are indicative of that the immunopathological reactions, which are typical of HBV patients, can be detected at the ocular level and they can provoke ophthalmic pathologies. The nature, severity and relation between the local and systematic immune disorders predetermine, to a considerable extent, the development of an eye disease and its severity. The treatment (and prophylaxis) of HBV-associated ophthalmic pathologies require an obligatory usage of immunity-correcting means and clinical-and-immunological monitoring.

Adjuvants, Immunologic↗

PubMed1990

Lymphokine release, suppressor cell generation, cell surface markers, and cytotoxic activity in cancer patients receiving natural interleukin-2.

We monitored patients treated for 5 days with continuous infusion of increasing doses (3 to 6 x 10(6) U/d) of natural interleukin-2 (IL-2). CD16+, CD25+, and CD56+ cells increased after treatment. Plasma tumor necrosis factor-alpha (TNF-alpha) levels, but not interferon-gamma (IFN-gamma) levels, increased during IL-2 treatment, but spontaneous and IL-2-stimulated TNF-alpha secretion in vitro remained abnormally low. However, mitogen-stimulated TNF-alpha release was normal. Mitogen-stimulated, but not IL-2-stimulated, IFN-gamma release was strongly depressed. Low spontaneous and IL-2-stimulated cytotoxicity on K562 or Daudi increased after treatment. Low suppressor cell generation also normalized after treatment. This appears to be the first reported study of immunologic monitoring of cancer patients treated with natural rather than recombinant IL-2.

Antigens, Differentiation↗

PubMed1993

Immunotherapy for respiratory allergic diseases: indications, efficacy and monitoring.

The author reports a detailed analysis of the indications for Specific Immuno-Therapy (SIT) in allergic rhinitis and asthma. After pointing out the requirements for a correct clinical trial, the efficacy of SIT towards various allergenic agents is examined (pollen, mites, cat and dog danders, moulds). Clinical monitoring--by means of clinical diaries, symptom score, drug consumption, skin tests, challenge tests--and immunological monitoring--by means of measuring of IgE and IgG serum antibodies, mediator and cytokine release, lymphocyte study, etc.--are then discussed. Immunological and clinical parameters to evaluate the efficacy of SIT are compared: clinical parameters being the most effective means of evaluation of clinical improvement.

Allergens↗

PubMed2000

Immunomodulatory therapies in sepsis.

Despite advances in critical care medicine, mortality from sepsis in ICU patients remains high. In response to several infectious and non-infectious stimuli, monocytes/ macrophages release a number of mediators, including cytokines, involved in the proinflammatory response that underlies sepsis. The excessive release of these mediators results in the development of whole body inflammation, and plays an important role in the pathogenesis of sepsis and septic shock. In addition, patients with sepsis also undergo an anti-inflammatory phase (the compensatory anti-inflammatory response syndrome) and at times, a mixed response with both pro-and anti-inflammatory components (the mixed antagonistic response syndrome). The initial systemic hyperinflammation is caused by production of inflammatory cytokines, especially tumour necrosis factor-a (TNF-alpha), and also interleukin-1 (IL-1), IL-6, and interferon gamma, which act synergistically with TNF-alpha in inducing shock in animal models. However, clinical trials aimed at downregulating these mediators using antibodies against endotoxin, TNF-alpha, antagonists of IL-1 or platelet activating factor have proved to be uniformly disappointing. Not only have these agents been found to have no effect, but they may also increase mortality. One of the reasons for such failure may be the lack of precise immunological monitoring during the course of sepsis. We have recently demonstrated that sepsis shows a biphasic immunological pattern during the initial and later phase: the early hyperinflammatory phase is counterbalanced by an anti-inflammatory response which may lead to a hypoinflammatory state. The latter is associated with immunodeficiency that is characterised by monocytic deactivation, so-called immunoparalysis. Interferon gamma-1 b has an immunoregulatory effect in patients with immunoparalysis during the compensatory anti-inflammatory response syndrome, not only restoring levels of HLA-DR expression but also reestablishing the ability of monocytes to secrete cytokines such as TNF-alpha. By monitoring immune status in septic patients, targeted intervention may lead to more success in immunomodulation of sepsis.

Animals↗

PubMed1985

[Intrafamilial renal transplantation in children after donor blood transfusions].

This article represents an update of our experience with deliberate donor specific blood transfusions (D.S.T.) prior to living-related renal transplantation in children. Eighteen recipients with a negative cross- match to donor T and B cells entered the D.S.T. protocol without regard to the results of the mixed lymphocyte cultures and third party transfusion. The D.S.T. procedure involves the administration of fresh packed cells on 2 or 3 separate occasions at 4 weeks intervals. The potential recipient's sensitization is closely monitored against donor's isolated T and B lymphocytes and against a random panel. This immunological monitoring is done 10 to 20 days after each D.S.T. and just prior to grafting. A negative T and B cross-match at 37 degrees C is a pre-requisite for transplantation. Sixteen patients have been transplanted. All kidneys are functioning with follow-ups ranging from 6 to 48 months; 10 patients have normal renal function, 2 of them experienced reversible acute rejection and 6 have chronic rejection. The benefits derived from pretransplant D.S.T. in parental renal transplantation appear to be substantial, although the nature of the various immunological mechanisms remains unclear.

Adolescent↗

PubMed1977

Lymphocyte monitoring as a predictor of renal allograft rejection.

The ability to predict acute renal allograft rejection episodes or infectious potentials by immunologic monitoring was studied in 15 renal transplant recipients. Specifically, total circulating erythrocyte- (E) and erythrocyte-antibody-complement (EAC) rosetting cells were serially studied for the first two months after transplantation and related to immunosuppressive therapy and rejection activity. Total circulating, E-rosetting cells (T cells) were noted to be significantly depressed if rabbit anti-human thymocyte globulin (RAHTG) was used in the immunosuppression protocol. The rate at which these T cells repopulated the circulation was measured by calculating their slope (delta total E-rosettes/delta time). Patients with acute rejection had an average slope of 3.2 +/- 0.68 compared to those without rejection, whose slope was 0.74 +/- 0.35 (p less than 0.01). The rapid repopulation of T cells occurred about 10 days before clinical parameters of rejection were evident. The incidence of infection was greater in those patients with total E-rosettes less than 200/mm3. Serial monitoring of total E-rosetting cells after transplantation provides a diagnostic tool for predicting ensuing rejections and can also be used to gain information concerning the susceptibility to infection.

Adolescent↗

PubMed1991

Sequential dacarbazine/cisplatin and interleukin-2 in metastatic melanoma: immunological effects of therapy.

Thirteen previously untreated patients with metastatic melanoma entered into a phase II chemo-immunotherapy trial were monitored immunologically during treatment. Treatment consisted of dacarbazine (DTIC) 750 mg/m2 and cisplatin 100 mg/m2 on day 1 followed by interleukin-2 (IL-2) 4 x 10(6) U/m2 by daily intravenous bolus on days 12-16 and 19-23. Cycles were repeated every 28 days. On days 1 (pretreatment), 12, 16, and 23 of each cycle, lymphokine-activated killer (LAK) cell and natural killer cell activity as well as total lymphocyte count and CD3, CD4, CD8, and CD56 lymphocyte subsets were analyzed. Despite pretreatment with full-dose cytotoxic chemotherapy, all patients were able to respond immunologically to IL-2. Spontaneous LAK cell activity was generated by the end of each course of IL-2 administration and persisted for at least 5 days thereafter. Lymphocytosis was maximum at 5 days after IL-2 administration and included increased numbers of all measured lymphocyte subsets. IL-2 administration caused a relative increase in CD56+ cells and a relative decrease in CD3+ cells. There was a direct correlation between the increase in LAK cell activity and the increase in CD56+ lymphocytes. Antitumor responses occurred in five patients but these responses did not correlate with any of the measured changes in LAK activity or lymphocyte subsets. DTIC and cisplatin administered in this schedule does not abrogate the immunological effects of IL-2.

Adolescent↗

PubMed1981

Immunological and pharmacological monitoring in the clinical use of cyclosporin A.

Immunological reactivity to donor antigens and serum concentrations of cyclosporin A were monitored in six patients after renal transplantation. At concentrations of 0.1--1.0 microgram/ml cyclosporin A prevented both donor-specific immune reactivity and clinical rejection during the early post-transplant course. Measurement of cyclosporin A levels and immunological indices allowed individual adjustment of the dosage so as to give excellent early graft function with few adverse effects.

Cyclosporins↗

PubMed2003

The Granzyme B ELISPOT assay: an alternative to the 51Cr-release assay for monitoring cell-mediated cytotoxicity.

BACKGROUND: The interferon-gamma (IFN-gamma) ELISPOT assay is one of the most useful techniques for immunological monitoring of cancer vaccine trials and has gained increased application as a measure of specific T cell activation. However, it does not assess cell-mediated cytotoxicity directly as IFN-gamma secretion is not limited to only cytolytic cells. Granzyme B (GrB) is a key mediator of target cell death via the granule-mediated pathway. Therefore, the release of GrB by cytolytic lymphocytes upon effector-target interaction may be a more specific indicator of CTL and NK cytotoxic ability than IFN-gamma secretion. METHODS: We assessed whether the GrB ELISPOT assay is a viable alternative to the 51Cr-release and IFN-gamma ELISPOT assays for measuring antigen-specific CTL cytotoxicity. Direct comparisons between the three assays were made using human CTL cell lines (alphaEN-EBV and alphaJY) and an in vitro stimulated anti-Flu matrix peptide (FMP)-specific CTL. RESULTS: When the GrB ELISPOT was directly compared to the IFN-gamma ELISPOT and 51Cr-release assays, excellent cross-correlation between all three assays was shown. However, measurable IFN-gamma secretion in the ELISPOT assay was observed only after 1 hour of incubation and cytotoxicity assessed via the 51Cr-release assay after 4 hours, whereas GrB secretion was detectable within 10 min of effector-target contact with significant secretion observed after 1 h. Titration studies demonstrated a strong correlation between the number of effector cells and GrB spots per well. Irrelevant targets or antigens did not induce significant GrB secretion. Additionally, GrB secretion was abrogated when CTL cultures were depleted of CD8+ cells. CONCLUSION: Our findings demonstrate that the GrB ELISPOT assay is a superior alternative to the 51Cr-release assay since it is significantly more sensitive and provides an estimation of cytotoxic effector cell frequency. Additionally, unlike the IFN-gamma ELISPOT assay, the GrB ELISPOT directly measures the release of a cytotolytic protein. Detection of low frequency tumor-specific CTL and their specific effector functions can provide valuable insight with regards to immunological responses.

Journal Article↗

PubMed1992

Use of monitored CD4 cell counts: predictions of the AIDS epidemic in Scotland: CD4 Collaborative Group.

OBJECTIVE: We describe the CD4 database of the Scottish Immunology Laboratories, and its uses and limitations for making short-term predictions of a CD4 cell count less than or equal to 200 x 10(6)/l (CD4(200)) and of adult AIDS cases in Scotland. DESIGN: The date of the earlier of two consecutive samples (typically 3 months apart) both with CD4 cell counts less than or equal to 200 x 10(6)/l was taken to define when a patient had passed the CD4(200) threshold (referred to as a CD4(200) case). The CD4 database comprises HIV-1-seropositive adults in the four main risk groups [homosexual/bisexual (1), injecting drug users (IDU; 2), heterosexual contact (3), and undetermined (9)] from Scotland's three principal areas of population (Lothian, Tayside and Strathclyde) who have had a CD4 cell count of less than or equal to 500 x 10(6)/l. SETTING: Three hospitals in Scotland, the Communicable Diseases (Scotland Unit) and the Medical Research Council Biostatistics Unit, Cambridge, UK. PATIENTS, PARTICIPANTS: The CD4 database at 31 December 1990 listed 813 patients (of whom 52% were IDU): 390 were CD4(200)/AIDS cases (of whom 44% were IDU) and 192 were AIDS cases (of whom 32% were IDU). RESULTS: Individuals in risk groups 1, 2 and 3 were nearly equally represented among newly diagnosed HIV-1 infections in 1990. However, among patients with moderate immunodeficiency, IDU accounted for 50% of the total number. Co-incidence of first CD4 cell count with CD4(200) diagnosis was recorded for only 28% of IDU, but in over 50% of cases for each of the other exposure groups (57%). There was a highly significant decrease of around 80 x 10(6)/l per calendar-year-of-referral in first CD4 cell counts for patients on the CD4 database; and decreases of around 40 x 10(6)/lper decade of age at referral. Since 1988, median time from CD4(200) to AIDS diagnosis in Scotland has been approximately 2 years. Back-projection was applied to annual CD4(200)/AIDS diagnoses before 31 December 1990 and to AIDS diagnoses. From AIDS diagnoses, the central epidemic scenario underestimated past HIV-1-antibody-positive reports (up to the end of 1985). More dramatic underestimation was occasioned by back-projection from CD4(200)/AIDS diagnoses [319 inferred HIV infections compared with 445 HIV-1-antibody-positive reports to Communicable Diseases (Scotland) Unit]. CONCLUSIONS: First CD4 cell counts should complement new HIV-1 diagnoses. Past referrals for immunological monitoring were not uniform between risk groups in Scotland. Underascertainment of CD4(200) cases is a problem when CD4(200) cases are used as a basis for back-projection. More information concerning the incubation distribution from HIV seroconversion to CD4(200) diagnosis is required. It is likely that there are twice as many CD4(200)/AIDS as there are diagnosed cases of AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1977

Monitoring and modulation of recipient immune responsiveness to prevent kidney graft rejection in the early post-transplant period.

In 41 consecutive living and cadaver donor renal transplant recipients, immunological monitoring was performed 2--3 times a week for the first two post-transplant months. Monitoring consisted of: 1) Circulating T and B cell levels (E-EAC Rosette assay) 2) T cell reactivity (PHA-Con A) 3) LMC and ADCC reactivity Rejection was diagnosed by standard techniques including radioisotope renal scans and biopsy in some cases. Immunosuppression consisted of prednisone, imuran, cyclophosphamide and horse ALG. In 32 rejection episodes in the first two months, 22 (68%) were associated with a rise in T cell levels. Rejection activity also correlated with an augmented PHA mitogenesis count of 20 +/- 5%. There was no positive correlation between Con A mitogenesis and rejection. There was also no correlation between rejection and circulating B cell levels. There was no significant correlation between a positive ADCC and graft rejection. Futhermore a positive ADCC in association with a negative LMC resulted in excellent long-term graft function. In conclusion, an excellent correlation of levels of circulating T cells and T cell reactivity with early in vivo rejection was shown.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1990

Treatment of metastatic melanoma with an autologous tumor-cell vaccine: clinical and immunologic results in 64 patients.

We treated 64 patients with metastatic melanoma using a melanoma vaccine preceded by low-dose cyclophosphamide (CY), and monitored immunologic effects and antitumor activity. On day 0, the patients were given CY 300 mg/m2 intravenously. Three days later, they were injected intradermally with vaccine consisting of 10 to 25 x 10(6) autologous, enzymatically dissociated, cryopreserved, irradiated (25 Gy) tumor cells mixed with bacillus Calmette-Guérin (BCG). This treatment sequence was repeated every 28 days. Of 40 assessable patients with measurable metastases, five had responses, four complete and one partial, with a median duration of 10 months (7 to 84+ months). In six additional patients, we observed an antitumor response that seems to be peculiar to this vaccine therapy: the regression of metastatic lesions that appeared after the immunotherapy was begun. Delayed-type hypersensitivity (DTH) to autologous, mechanically dissociated melanoma cells that had not been exposed to extraneous antigens, such as enzymes or fetal calf serum, increased significantly following immunotherapy (day 0 v day 49, P less than .001; day 0 v day 161, P less than .001; day 0 v day 217, P = .021). Antitumor responses to the vaccine were strongly associated with DTH, as indicated by three observations: (1) eight of 10 patients who exhibited tumor regression had positive DTH, (2) in postsurgical adjuvant patients, there was a highly significant linear relationship (P less than .001) between the intensity of DTH to autologous melanoma cells and the time to recurrence of tumor, and (3) nine patients who developed DTH to the autologous melanoma cells in their original vaccine developed new metastases that failed to elicit DTH or elicited a much smaller response. In three cases, we were able to excise regressing tumors for histologic examination; such tumors were characterized by an intense infiltration of lymphocytes. This demonstration that an immune response to melanoma-associated antigens can be elicited in cancer-bearing patients provides some basis for optimism about the prospects for developing active immunotherapy that has practical therapeutic value.

Adult↗