SEARCH · PubMed Health

Results for “Monitoring, Immunologic”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources

PubMed1989

Sequential determinations of urinary cytology and plasma and urinary lymphokines in the management of renal allograft recipients.

Urine cytology, plasma (P), and urinary (U) interleukin-2 (IL-2)* and IL-2 receptor (IL-2R) levels were evaluated as immunological monitoring techniques in 65 renal allograft recipients. Normal individuals showed normal urine cytology, IL-2(U) = 0, IL-2(P) = 0.4 +/- 0.1 ng/ml (mean +/- SEM) and IL-2R(P) = 318 +/- 26 U/ml. Stable transplants also showed normal urine cytology, no IL-2(U), IL-2(P) = 0.8 +/- 0.2 ng/ml, and IL-2R(P) = 326 +/- 29 U/ml. Rejection episodes (n = 21) were accompanied by cytologic changes, including lymphocyturia, exfoliation of immature tubular cells, platelet aggregates, and fibrin deposits. The corresponding lymphokine changes were IL-2(U) = 39.6 +/- 1.4 ng/ml, IL-2(P) = 79 +/- 21 ng/ml, and IL-2R = 1884 +/- 202 U/ml, all markedly increased. Successful treatment was associated with return of all parameters to normal; treatment failure was associated with continued abnormalities. Fourteen rejections unresponsive to Solumedrol (500 mg x 5 days) required OKT3 rescue (5 mg x 14 days). In the 11 that were reversed, onset of OKT3 therapy was characterized by markedly increased exfoliation of necrotic cellular debris, lymphocytes, and collecting duct cells. Interestingly, serum creatinine increases of 57.2 +/- 18.9% (range 25-90%) over pre-OKT3 levels were noted. Maximal changes occurred 48-72 hr after the first dose, followed by gradual return to normal. Rejections unresponsive to OKT3 (n = 3) showed no cytologic changes from the pretreatment mean creatinine increase of 13.2 +/- 2.7% (range 9-15%), and maximum change occurred 24 hr after the first dose. Rejections responsive to Solumedrol only (n = 4) showed gradual improvement of all parameters. Rejections treated with Solumedrol following failed OKT3 prophylaxis (n = 3) did not reverse and continued to show rejection associated cytologic changes and abnormal creatinines. Patients experiencing CsA toxicity (n = 12) showed mild creatinine elevations, normal or negative IL-2(P) and IL-2R(P) levels, and no IL-2(U). They showed distinctive cytologic changes consisting of swollen convoluted tubular cells with nuclear pyknosis and cytoplasmic vacuoles. Pretransplant IL-2(P) levels of patients who subsequently rejected were elevated, with 19/21 patients with preoperative IL-2 levels greater than 15 ng/ml having subsequent rejections. In contrast, pretransplant creatinine, urine cytology, and IL-2(U) levels showed no correlation to subsequent clinical course.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗

PubMed1989

Eosinophil granule major basic protein in acute renal allograft rejection.

Conventional staining techniques to determine the presence of tissue eosinophils underestimate their number and do not usually detect eosinophil degranulation. We have studied the involvement of eosinophils in acute renal allograft rejection by immunofluorescence localization of eosinophil granule major basic protein (MBP) in the kidney and by measurement of MBP in the plasma and urine by radioimmunoassay. Tissue eosinophilia and extracellular deposition of MBP indicative of eosinophil degranulation were observed in 94% and 87%, respectively, of patients with acute rejection as compared with 17% and 17%, respectively, of patients with cyclosporine nephrotoxicity. The urine levels of MBP were significantly elevated in acute rejection but not in cyclosporine nephrotoxicity. Plasma MBP concentrations were within the normal range in both acute rejection and cyclosporine nephrotoxicity. The presence of marked tissue eosinophilia and eosinophil degranulation did not always indicate irreversible rejection. Interleukin-2 and IL-2 receptors were also elevated in the urine during acute rejection. These results support a role for the eosinophil as an effector of tissue damage during rejection and suggest the potential usefulness of urine MBP determinations for the immunologic monitoring of transplanted patients.

Acute Disease↗

PubMed1990

Proliferative responses of bronchoalveolar lavage lymphocytes from heart-lung transplant patients.

Donor-specific alloreactivity of bronchoalveolar lavage (BAL) lymphocytes was evaluated in the immunologic monitoring of lung transplant patients. The study dealt with 161 BAL performed on 28 transplant recipients. Unseparated BAL cells, separated BAL lymphocytes, and PBL were tested for donor-specific proliferative responses in 3-day primed lymphocyte testing (PLT), and for nonspecific proliferative responsiveness to exogenous IL-2. The proliferation data were analyzed for correlation with the status of the lung allograft assessed clinically, histologically, and by pulmonary function testing. Positive PLT responses of BAL lymphocytes were observed in 20 of 22 acute rejection episodes (91%) and in 24 of 35 cases (69%) when chronic rejection was diagnosed. During clinical quiescence donor-specific proliferative activity was demonstrated in only 4 of 35 cases (11%). Thus, acute rejection and chronic rejection correlated significantly (P less than 0.001) with donor-specific PLT reactivity of BAL lymphocytes. Though significant association with rejection was observed for the alloreactivity of unseparated BAL cells and PBL, the sensitivity of the PLT test with these cells was significantly lower than that with BAL lymphocytes. Similarly, the IL-2 proliferative activity of BAL lymphocytes was significantly increased during acute and chronic rejection. However, this test had lower sensitivity and specificity than did the donor-specific PLT. These findings suggest the usefulness of the donor-specific PLT of BAL lymphocytes as a reliable method for monitoring pulmonary rejection.

Adolescent↗

PubMed1991

OKT3 therapy for hepatic allograft rejection. Differential response in adults and children.

The clinical courses following OKT3 therapy for hepatic allograft rejection (HAR) in adults and children have not been individually defined. We have reviewed our experience with OKT3 therapy for HAR in adults and children to compare: (1) the initial response to OKT3 therapy, (2) the clinical course following OKT3 therapy, and (3) the antimurine antibody response and immunologic monitoring results. Children required OKT3 therapy more frequently than adults: fourteen courses of OKT3 therapy were required in 130 orthotopic liver transplants (OLT) in 108 adult patients, whereas nineteen courses of OKT3 therapy were required in 94 OLT in 78 children (P less than 0.02). Repeat OKT3 therapy was not required in adults--however, four of nineteen courses of OKT3 therapy in children were repeat OKT3 therapy for rejection. No differences existed between adult and pediatric treatment groups with respect to number of prior OLT procedures, previous graft loss to rejection, percentage of ABO-incompatible grafts, frequency of positive donor-recipient lymphocyte crossmatches, or time to first rejection. The initial response to OKT3 therapy (rapid reversal, delayed reversal, and failure) was remarkably similar in adults and children. However, nine of 13 (70%) children with clear evidence of response to OKT3 treatment experienced breakthrough rejection or early recurrent rejection, whereas none of 12 adults suffered breakthrough rejection or early recurrent rejection (P less than 0.01). Early recurrent rejection did not correlate with delayed reversal of rejection, early return of CD3+ cells by peripheral blood monitoring, or development of anti-OKT3 antibodies. All 4 courses of OKT3 retreatment in children were successful in reversing rejection, and breakthrough rejection and early recurrent rejection did not occur. Overall graft and patient survival in pediatric patients requiring OKT3 therapy (67% and 73%) was not different from that in adults (71% and 79%). Results obtained in one patient provide the first evidence that successful OKT3 retreatment of HAR can be achieved in the presence of preexisting idiotypic anti-OKT3 antibody. In conclusion, OKT3 therapy for HAR was required more frequently in children than in adults. The clinical outcome following OKT3 therapy for HAR also differs markedly, with early recurrent rejection and breakthrough rejection occurring more frequently in children.

Adult↗

PubMed1996

Systemic administration of cellular interleukin-10 can exacerbate cardiac allograft rejection in mice.

Cellular interleukin-10 (cIL-10) has been shown to inhibit cytokine production by T helper type 1 (Th1) cells by blocking antigen presenting cell function. This activity has suggested that IL-10 might be useful in the treatment of transplant rejection. Stimulatory effects of IL-10 however, have also been observed both on T and B cell differentiation. In this study, we examined the influence of recombinant (r) mouse (m) IL-10 on heterotopic vascularized heart allograft survival in the B10(H2b)-->C3H(H2k) strain combination that crosses both major histocompatibility complex (MHC) and non-MHC-histocompatibility antigen (non-MHC-HA) barriers. The influence of IL-10 was also examined in the B10.BR (H2k)--> C3H combination with disparity at only non-MHC-HA loci. Postoperative intraperitoneal administration of IL-10 (100 microg/d, days 0-6) significantly accelerated heart graft rejection both in the B10-->C3H (mean survival time [MST] 7.8+/-0.2 days; control MST 10.6+/-0.6 days; P<0.05) and the B10.BR-->C3H combination (MST 14.3+/-0.5 days; control MST 77.7+/-14.4 days). Ex vivo IL-10 perfusion of donor hearts for either 15 min or 2 hr did not affect subsequent graft survival. Immunologic monitoring of transplanted mice revealed that IL-10 treatment (100 microg/d, i.p., days 0-6) increased both the circulating complement-dependent cytotoxic (CDC) antibody titer and splenic anti-donor cytotoxic T lymphocyte (CTL) activity measured up to 3 weeks posttransplant. These findings indicate that post transplant systemic administration of cIL-10 can promote vascularized allograft rejection, and that this may reflect stimulation both of B and T cell alloimmune responses.

Animals↗

PubMed1997

Urine flow cytometry as a tool to differentiate acute allograft rejection from other causes of acute renal graft dysfunction.

BACKGROUND: Recently, urine flow cytometry (UFC) was introduced as a useful noninvasive tool for the immunological monitoring of renal allograft recipients. The presence of an active urine sediment as determined by UFC was found to be associated with acute rejection (AR) episodes. METHODS: In the present study we assess the value of UFC in the setting of acute graft dysfunction. UFC was performed in 30 patients (32 events) at the time of admission to the hospital for the evaluation of rising creatinine (serum creatinine increment > or =0.6 mg/dl above baseline). UFC analysis was done blinded to the clinical diagnosis, and results were compared with the discharge diagnosis: AR, n=15; chronic rejection (CR), n=8; drug toxicity, n=4; urinary leak, n=2; recurrence of primary disease, n=1; lymphocele, n=1; and unknown, n=1. RESULTS: The presence of at least 5% of HLA-DR-positive cells and intercellular adhesion molecule-1-positive cells was detected in 100% and 53%, respectively, of the samples associated with AR (P<0.01 vs. others). The specificity value for the diagnosis of AR was: 100% for the presence of intercellular adhesion molecule-1 or CD3-positive cells and 88% for the presence of interleukin-2 receptor-positive or HLA-DR-positive cells. Half of the samples associated with CR had CD14-positive cells (P=0.03 vs. others) with a specificity value of 87.3%. The samples associated with drug toxicity, urological problems, or recurrence of primary disease were remarkable for the lack of expression of the antigens studied. CONCLUSION: UFC can clearly differentiate AR from other causes of acute renal allograft dysfunction. HLA-DR is revealed to be the most sensitive and intercellular adhesion molecule-1 the most specific marker for AR. The presence of CD14-positive cells was highly suggestive of CR. Due to its objective nature, UFC should be considered in the evaluation of graft dysfunction.

Acute Disease↗

PubMed1998

Life-supporting pig-to-primate renal xenotransplantation using genetically modified donors.

BACKGROUND: In order to circumvent the complement-mediated hyperacute rejection of discordant xenografts, a colony of pigs transgenic for the human regulator of complement activity, human decay-accelerating factor (hDAF), has been produced. METHODS: Seven kidneys from hDAF transgenic pigs and six kidneys from nontransgenic control pigs were transplanted into cynomolgus monkeys; both native kidneys were removed during the same operation. The recipient animals were immunosuppressed with cyclosporine, steroids, and cyclophosphamide. RESULTS: In the transgenic group, the median survival time was 13 days (range, 6-35 days); the median survival time in the control group was 6.5 days (range, 0.3-30 days). There were no cases of hyperacute rejection in the transgenic group, and the two longest-surviving kidneys in this group showed no evidence of rejection on histological examination. In contrast, all control kidneys underwent antibody-mediated rejection, one demonstrating hyperacute rejection and the others acute vascular rejection. CONCLUSION: This study demonstrates that (i) a kidney from an hDAF transgenic pig can support the life of a primate for up to 35 days (and also shows the basic physiological compatibility between the pig and nonhuman primate); (ii) nontransgenic kidneys are not routinely hyperacutely rejected; and (iii) the presence of hDAF on the kidney confers some protection against acute vascular rejection. Improved immunosuppression and immunological monitoring may enable extended survival.

Animals↗

PubMed1998

Complete withdrawal of immunosuppression in kidney allograft recipients: a prospective study in rhesus monkeys.

BACKGROUND: We previously reported the successful withdrawal of immunosuppression in kidney-allografted rhesus monkeys. Recipients had received pretransplant blood transfusions and cyclosporine (CsA) immunosuppression for 6 to 12 months. One animal is still alive at more than 15 years after transplantation. Our hypothesis was that the sharing of a single DR antigen between blood donor and recipient, and the sharing of the same DR antigen with the kidney donor, may be beneficial to allograft survival. We now report on the results from a prospective study. METHODS: The animals received three pretransplant blood transfusions from a single donor sharing one DR antigen with the recipient. Subsequently, a life-supporting kidney from a donor sharing the same DR antigen was transplanted. CsA was given for at least 6 months after transplantation. RESULTS: Two animals rejected their graft at 5-8 weeks after cessation of CsA treatment. One animal is still alive at 700 days after transplantation. This animal showed MLR nonreactivity to its kidney donor, similar to the animal at more than 15 years after transplantation. CONCLUSION: These results demonstrate that withdrawal of immunosuppression may be a realistic option in kidney graft patients under careful immunological monitoring of donor-specific immunity.

Animals↗

PubMed2001

Alterations of cell-mediated immunity following cardiac operations: clinical implications and open questions.

Cardiac surgery with cardiopulmonary bypass (CPB) is known to induce an immune response whose nature has been increasingly elucidated during the recent decade. Clinically, patients usually show two to three of the four symptoms, which define the so-called systemic inflammatory response syndrome (SIRS). In addition, all parameters of the innate, nonspecific immune system, e.g., polymorphonuclear cells, elastase, and complement, are activated. This also applies to the proinflammatory mediators interleukin (IL)-1beta, -6, and -8, and tumor necrosis factor (TNF)-alpha. Within the adaptive, specific immune system, a decrease of T lymphocytes and T helper (TH) cells is observed, whereas suppressor/ cytotoxic T cells and B cells appear to be nearly unaffected. Cytokine measurements provide more detailed information: IL-2 and IL-12, which are important for the activation of the type-1 TH-cell (TH1)-mediated immune response, are depressed following cardiac operation. In contrast, IL-10 and transforming growth factor-beta essential to TH2-mediated humoral or anti-inflammatory immune response, are upregulated. In vivo tests, e.g., delayed type hypersensitivity skin reaction and tetanus antibody production, confirm the polarization of the adaptive immune response towards the TH2 pathway. However, all these alterations usually do not result in clinical adverse events. Therefore, more information is needed about the immune response of patients at high preoperative risk or with serious perioperative complications to find out whether clinically relevant events are correlated to alterations of immune response. For this purpose, more readily available, standardized methods for immunologic monitoring appear highly desirable.

Cardiac Surgical Procedures↗

PubMed1995

Combined kidney and pancreas transplantation.

Diabetes is the leading cause of end-stage renal disease in the United States. Combined kidney and pancreas transplantation is a safe and effective treatment option for diabetic nephropathy. During the past decade, pancreas transplants had improved outcomes as a result of improvements in pancreas recovery and preservation, the surgical procedure, immunosuppressive regimens, and immunologic monitoring. Current 1-year patient and graft survival rates are 90% and 80%, respectively, and evidence is accumulating that improvements occur in microvascular and neuropathic complications as well. Successful outcomes of kidney and pancreas transplantation are due in large part to careful nursing assessment, diagnosis, intervention, teaching, and discharge planning.

Humans↗

PubMed2002

Hematopoietic growth factors, dendritic cell biology, and vaccine therapy of cancer.

Hematopoietic growth factors have made it possible to collect, manufacture, and engineer dendritic cells ex vivo for clinical use and expand dendritic cell subsets in vivo when administered to patients. Dendritic cells are important vectors in the induction of an effective immune response against infection and neoplastic disease. Antigens alone, even those preprocessed to bind to antigen-presenting major histocompatibility complex class I and II molecules, are insufficient to regulate effective T-cell-mediated immunity. Activated dendritic cells are essential to this task. Studies of dendritic cell biology in the laboratory and preclinical studies have facilitated the implementation of clinical trials using dendritic cells in the treatment of melanoma and other cancers. Dendritic cell subset functional differences, effective tumor target antigen loading of dendritic cells for presentation to immune effector cells, dendritic cell maturation, the route of dendritic cell administration to humans, and immunologic monitoring are parameters that require vigorous study in the context of dendritic cell immunotherapy of cancer.

Animals↗

PubMed2004

Metastable tolerance in nonhuman primates and humans.

It is clear that both humans and nonhuman primates can do without immunosuppression for long periods of time before rejecting their allogeneic organ transplants. Immune cell depletion, particularly lymphocyte depletion, is an effective clinical strategy for achieving a tolerant state. Based on nonhuman primate and human studies, evidence suggests that metastable tolerance develops over time in a donor-specific manner and is mediated at least in part by donor antigen-specific regulatory T cells. Suppression of effector T cells by CD8+ and CD4+ T-regulatory cells is mediated by transforming growth factor (TGF)-beta or interleukin 10, and the presence of CD4+ TGF beta(latent) T-cell infiltrates may be a useful diagnostic marker for metastable tolerance. Loss of these cells has been shown to correlate with loss of tolerance. Future efforts to withdraw immunosuppressive drugs and establish a tolerant state will depend importantly on development of such diagnostic immunologic monitoring tools. Some of the reasons that tolerance remains such a challenging goal in clinical transplantation are discussed herein.

Animals↗

PubMed2005

Development of tolerogenic strategies in the clinic.

The study of tolerance in the clinic can be divided into three areas: (i) focused evaluation of existing tolerant transplant recipients as to their mechanism of tolerance; (ii) prospective tolerance trials, such as combined bone marrow and kidney transplantation as well as T cell depletion followed by subsequent weaning of immunosuppression; and (iii) immunologic assays to assess the likelihood of rejection or tolerance. Frankly, a very small number of patients have been transplanted with the intention of removing all immunosuppressive therapy, but several clinical trials with this aim are currently in progress, largely sponsored by the Immune Tolerance Network, a joint venture between the National Institutes of Health and the Juvenile Diabetes Research Foundation. Similarly, a reliable assay to assess tolerance has not yet been developed but a variety of approaches towards assessing rejection, and in some cases tolerance, are being developed. It would be accurate to state that many of the experimental and preclinical approaches to the induction of tolerance have resulted in better immunosuppression for human transplantation, but reliable tolerance strategies in humans have not yet been achieved. Combined bone marrow and kidney transplantation may be considered as one exception to this, but such a strategy is not generally applicable to the vast majority of solid organ transplant recipients. This review will summarize efforts to date, particularly focusing on kidney transplantation.

Humans↗

PubMed1992

Acute rejection in heart transplant patients is associated with the presence of committed donor-specific cytotoxic lymphocytes in the graft but not in the blood.

In vivo-activated, committed donor-specific cytotoxic lymphocytes (cCTL) can be propagated and expanded from endomyocardial biopsies (EMB) in IL-2-enriched medium especially during an acute rejection episode. We report here our efforts to detect these cCTL by the same technique in peripheral blood at the moment of rejection and when no rejection was diagnosed. During or just before rejection, significantly less frequent (P less than 0.01) donor reactive cCTL were found in PBL samples (two out of 20) than in the simultaneously taken EMB samples (13 out of 19). Donor B-LCL and/or third-party B-LCL were lysed by 15 PBL samples. Inhibition studies revealed that this lysis was due to LAK-like cytotoxicity. The results show that peripheral blood does not reflect intra-graft events, which is probably the reason for the irreproducible results of diagnosis of rejection by monitoring immunological parameters in the peripheral blood.

Biopsy↗

PubMed1988

Oral zinc supplementation in Down's syndrome: restoration of thymic endocrine activity and of some immune defects.

Eighteen non-institutionalized Down's syndrome (DS) children (mean age: 7.0 +/- 10/12 years) with a history of respiratory tract, auditory and skin infections, low plasma levels of a nonapeptide thymic hormone, i.e. Serum Thymic Factor (STF), high plasma levels of inactive zinc-unbound STF molecules, and reduced absolute number of circulating T-lymphocytes, were given an oral non-pharmacological supplementation of zinc sulphate (1 mg Zn++/kg body weight/day for 2 months; two cycles, 10 months apart) and monitored immunologically before and after each cycle. A dramatic increase of plasma STF level and concomitantly an almost complete disappearance of inactive STF molecules was observed after each cycle. The absolute number of circulating T-lymphocytes was significantly increased by zinc treatment. The marginal zinc deficiency was also corrected without any appreciable influence on copper plasma levels. A reduction of recurrent infections and an improvement in school attendance after zinc supplementation were recorded. These beneficial effects of zinc supplementation were also noted in those DS children who did not show an apparent zinc deficiency, as assessed by measuring zinc plasma level. The reduced number of circulating B lymphocytes and the impaired lymphocyte responsiveness to phytohaemagglutinin and concanavalin A were not restored. On the whole, these findings suggest that there exists a defect in the bio-availability and/or in the utilization of zinc in DS. This alteration, of unknown origin, can be underestimated on the simple basis of the zinc plasma level and can be corrected with moderate nutritional zinc supplementation.

Child↗

PubMed2005

Infectious risk in pediatric organ transplant recipients: is it increased with the new immunosuppressive agents?

The risk of infection in pediatric organ transplant recipients is determined by several factors, including age, the types of organ transplanted and the immunosuppressive treatment which has dramatically changed over the past 10 yr. Little information has been reported regarding the infectious complications related to the current immunosuppressive protocols used in these children. This paper reviews (i) the immunosuppressive agents, focusing on their mechanisms of action and on the new regimens, (ii) the infections related to excessive immunosuppression and also anti-infectious properties or infectious adverse reactions associated with specific immunosuppressive agents. With the new immunosuppressive protocols, the advances in immunologic monitoring, microbiological diagnosis, anti-infectious prophylactic and preemptive treatments, strategies to minimize the risk of infection related to the immunosuppressive therapy are proposed.

Child↗

PubMed2004

Safety of rituximab therapy during the first trimester of pregnancy: a case history.

The optimal treatment of non-Hodgkin's lymphoma (NHL) during pregnancy is currently undefined. The potential teratogenic effects of conventional chemotherapy preclude its use during the first trimester of pregnancy. We report the case of a pregnant woman with relapsed indolent follicular NHL who was treated with rituximab (unintentionally) during the first trimester. The treatment stabilised the disease. Following an uncomplicated pregnancy, a healthy child was born at full term and careful haematological and immunological monitoring has revealed no adverse effects resulting from exposure to rituximab. Data of using rituximab during pregnancy are scarce, but the present case shows that rituximab may be one option for treatment of NHL in early pregnancy.

Adult↗

PubMed1998

Intramolecular and intermolecular spreading during the course of organ allograft rejection.

There are two distinct pathways by which T cells may recognize MHC alloantigens. The direct pathway involves T-cell recognition of intact MHC molecules expressed by donor antigen-presenting cells (APCs). The second, or indirect, pathway describes T-cell recognition of peptides derived from the processing and presentation of allogeneic MHC molecules on self APCs. Recent data demonstrates that indirect recognition plays a central role in both acute and chronic rejection of human organ allografts. Our studies have shown that, at the onset of primary acute rejection, recipient T-cell responses to donor HLA-DR alloantigens are limited to a single dominant determinant present on one of the disparate alloantigens and restricted by one of the responder's HLA-DR molecules. In allograft recipients with recurring episodes of rejection, and/or at the onset of chronic rejection, recipient T-cell reactivity may spread to other epitopes within the allogeneic MHC molecule as well as to other alloantigens expressed by graft tissue. Both quantitative and qualitative alterations in T-cell allopeptide reactivity are associated with increased risk of cellular and/or humoral rejection. These studies provide a basis for the design of new therapeutic strategies and for immunologic monitoring of transplant recipients.

Graft Rejection↗