Immunologic monitoring of the renal transplant recipient.
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The aim was to study the value of the CAP system (Pharmacia) in comparison with the FAST method (Bio Whittaker) in determination of total IgE, specific IgE and IgG4 during specific immunotherapy (sIT). The studies were carried out on a group of 67 patients with pollinosis treated with various pollen allergen extracts. The immunological studies were performed before and after several courses of sIT. A higher reproducibility and sensitivity of the CAP System was shown. The values of specific IgE were somewhat higher on using the CAP system than using the FAST method. The CAP system seems to be of great value in diagnostics and monitoring sIT, especially in birch pollen allergy.
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We have already reported on the usefulness of the phytohemagglutinin (PHA) skin test and the purified protein derivative (PPD) skin test in predicting the prognosis of brain tumor patients. This paper outlines our investigation of T-lymphocyte subpopulations and analysis of their utilization. The cellular immunological states of brain tumor patients were examined by means of PHA and PPD skin tests, the blastogenic response of T-lymphocytes to PHA and the T-lymphocyte subpopulations. Our subjects consisted of 10 cases of glioma (8 astrocytoma, 2 ependymoma), 2 cases of meningioma, one of teratoma, one of hemangioblastoma and 4 of metastatic brain tumor. These were divided into 2 groups: the benign group, which included low grade astrocytoma, meningioma, teratoma and hamangioblstoma, and the malignant group which included malignant glioma and metastatic brain tumor. The T-lymphocytes were counted by monoclonal antibody assay using Ortho-mune T-lymphocyte monoclonal antibody (OK series). We then counted an analysis to determine metastatic brain tumor. The T-lymphocytes were counted by monoclonal antibody assay using Ortho-mune T-lymphocyte monoclonal antibody (OK series). We then conducted an analysis to determine whether or not the T-lymphocyte subpopulations could be of value in the prediction of the possible prognosis of patients. The results were as described below. Ratio of helper/inducer T-lymphocytes (OKT 4 positive cells: Th) to suppressor/cytotoxic T-lymphocytes (OKT 8 positive cells: Ts) were 1.78 +/- 0.18 in the benign group and 1.00 +/- 0.49 in the malignant group.(ABSTRACT TRUNCATED AT 250 WORDS)
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Despite the longstanding clinical use of azathioprine as an immunosuppressive agent in multiple sclerosis, little is known about the action of this drug on a number of parameters of putative pathogenic relevance in the disease. Eleven patients with multiple sclerosis, treated with azathioprine 2.5-3 mg/kg per day, and six untreated patients were studied with serial blood sampling for 1 year. The following immunological parameters were investigated: peripheral blood lymphocyte subsets, natural killer activity, serum IgG, IgM, ICAM-1 and tumour necrosis factor alpha (TNF-alpha). The most relevant changes included a decrease in CD3- CD56+ cells, an increase in CD4+ CD45RA+ cells and a decrease in TNF-alpha levels only in treated patients, while no changes occurred in untreated patients over a 1-year period. The decrease in TNF-alpha levels and the increase in "suppressor-inducer" lymphocytes could reduce chronic inflammation in multiple sclerosis, and paralleled an overall favourable clinical response to azathioprine treatment in our patients.
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Two-color flow cytometry was used to measure lymphocyte activation antigens, IL-2 receptor (IL-2R), and HLA-DR, on T helper/inducer and cytotoxic/suppressor subsets in the peripheral blood of cardiac transplant patients. Data including 213 cardiac biopsies to determine rejection were obtained on 24 consecutive recipients receiving cyclosporine and prednisone, who survived greater than 5 weeks. The results showed a correlation between the presence of CD4(T4)-IL-2R and rejections or infection occurring within the first 5 weeks posttransplantation. Sensitivity was 79% (73% for rejection only) specificity 97%, P less than .001 by Fisher's exact test. The number of T4-IL-2R cells peaked at 213 cells/microliter with a mean lead time of approximately 3 days prior to positive biopsy (n = 8). After 5 weeks posttransplantation, the sensitivity decreased to 35% (25% rejection only). This decrease may be due to the lack of samples immediately prior to biopsy in patients after 5 weeks posttransplantation. CD8(T8)-IL-2R, T8-DR, T4-DR levels did not correlate with rejections. The results suggest that T4-IL-2R cells that escape cyclosporine inhibition are highly correlated with rejection and enumeration may contribute to increased utility of immune monitoring in these patients.
Sequential monitoring of non specific immunity has been carried out in 16 patients with squamous cell bronchogenic carcinoma undergoing radical surgery. At the time of diagnosis total lymphocyte counts, T-lymphocyte counts and the blastogenic response of lymphocytes to PHA were only slightly depressed; on the contrary C3c and C4 serum levels were significantly increased (P less than 0.01). Sequential determinations of the immunologic profile at monthly intervals up to the 12th postoperative month showed a transient increase of total lymphocyte and T-lymphocyte levels; the lymphocyte blastogenic response to PHA and also C3c and C4 serum levels progressively decreased. Delayed hypersensitivity response to cutaneous antigens, neutrophil chemotaxis, serum levels of IgG, IgA, IgM and B-lymphocyte counts were constantly found within normal range.
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BACKGROUND: Additive antitumor effects could be achieved by combination of immunotherapy and cytotoxic agents with no or minimum suppression. METHODS: Thirteen patients positive for human leukocyte antigen (HLA)-A24 or -A2 with metastatic hormone refractory prostate cancer (HRPC) who had failed to respond to the prior-peptide vaccination were entered in the combined peptide vaccination and estramustine phosphate. Conducted immune monitoring on those 13 patients were mainly peptide-specific cytotoxic T lymphocyte (CTL) precursor analysis by IFN-gamma productions and peptide-reactive IgG by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Grade 3 arrhythmia or cerebral infarction was observed in two cases, and Grade 1 or 2 dermatologic reaction at the vaccination sites was observed in all 13 cases. Eleven patients who received more than one cycle of treatment were eligible for immunological and clinical evaluation. There was no significant immunosuppression in most cases when the peptide and a half dose (280 mg/day) of estramustine were administrated, whereas severe immunosuppression was observed in the first two patients who received both the peptide and a full dose (560 mg/day) estramustine. Augmentation of peptide-specific CTL precursors or peptide-specific IgG was observed in 6 of 11 or 10 of 11 cases, respectively. Ten of 11 patients showed serum prostate-specific antigen (PSA) level decrease from the baseline including 8 patients with a serum PSA level decrease of > or =50%. CONCLUSIONS: These results encouraged the further evaluation of the combination of peptide vaccination and low-dose estramustine phosphate for metastatic HRPC patients.
15 patients with progressive Multiple Sclerosis (MS) were treated by an induction Cyclophosphamide (CFX) schedule followed by bimonthly boosters over one year. Of the 14 patients who completed the trial, only two displayed worsening of neurological status. Cerebrospinal fluid (CSF) total protein, IgG/Alb ratio and IgG index decreased at 6 months and were still low at the end of the treatment. Pretreatment percentages of PB CD8+ and CD4+CD45RA+ lymphocytes were lower in MS patients in comparison with healthy controls. However, no significant shifts occurred in percentage of PB CD4+, CD4+CD45RA+, CD4+CD45RA-, CD8+ lymphocytes of MS patients during immunosuppressive treatment. The lack of changes in the investigated immunological parameters contrasts with the good clinical response and the low rate of serious side effects during this treatment schedule.