Assessment of Plasma Neopterin in Clinical Kidney Transplantation

Schäfer, Annika; Daniel, Volker; Dreikorn, K.; Opelz, Gerhard

doi:10.1097/00007890-198604000-00008

Cited by 77 publications

(39 citation statements)

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“…Plasma neopterin was measured initially with the neopterin-RIAcid assay and since 1995 with the Neopterin ELISA (Brahms, Berlin, Germany). Based on control measurements in 70 healthy individuals, we considered > 15 nmol/L abnormally high for both tests (54).…”

Section: Methodsmentioning

confidence: 99%

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Associations of blood levels of PCB, HCHS, and HCB with numbers of lymphocyte subpopulations, in vitro lymphocyte response, plasma cytokine levels, and immunoglobulin autoantibodies.

Daniel¹,

Huber²,

Bauer³

et al. 2001

Environ Health Perspect

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Pentachlorophenol (PCP), hexachlorocyclohexane-[alpha], -beta, and -[gamma] (HCH-[alpha], -beta, and -[gamma]), polychlorinated biphenyls (PCBs), and hexachlorobenzene (HCB) are widely distributed industrial chemicals. They are suspected to induce immunologic impairments in exposed individuals. We examined dose-response relationships of blood levels of these chemicals with cellular (numbers of lymphocyte subpopulations, in vitro lymphocyte response) or humoral (plasma cytokine levels, immunoglobulin autoantibodies) immunologic dysfunctions. We studied 146 patients who had been occupationally exposed primarily to PCBs for more than 6 months. Lymphocyte subpopulations, in vitro responses to mitogens and allogeneic stimulator cells, plasma neopterin, cytokines, soluble cytokine receptors, soluble adhesion molecules, anti-Ig autoantibodies, and liver transaminases were determined. Blood levels of the different compounds were strongly correlated with one another. There were only weak dose-response relationships between blood levels of PCBs with cellular immune parameters, and of HCHs and HCB with humoral immune parameters. An exception was the statistically significant negative association of HCB with interferon-[gamma] (IFN-[gamma]), indicating that HCB has a significant impact on Th1 lymphocytes. Patients with HCB blood levels above the mean of 1,109 ng/L more often had undetectable IFN-[gamma] blood levels than patients below the mean. Patients with increased PCB 138 (> 710 ng/L) had more frequently undetectable interleukin-4 blood levels than patients with PCB 138 below the mean, and patients with increased PCB 101 (> 31 ng/L) more often had low DR+ cell counts in the blood (< 190/microL) than patients with PCB 101 below the mean. To assess possible cumulative effects, we compared patients who had blood levels of all compounds below background with patients who had blood levels of all compounds above background. Patients with low or absent blood levels of the compounds studied had higher IFN-[gamma] plasma levels, providing some evidence for a cumulative effect of several weakly active compounds. In conclusion, exposure to PCBs, HCB, or HCHs is associated with weak immunologic abnormalities. These results contrast with those obtained in earlier studies of blood levels of PCP, which showed a strong dose-dependent relationship with immunologic impairments. Our data suggest that long-term exposure of patients to HCB suppresses IFN-[gamma] production.

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Section: Methodsmentioning

confidence: 99%

“…Anti-Ig autoantibodies were determined as previously described (54). We coated 96-well microtiter plates (Nunc, Roskilde, Denmark) at 37°C for 16 hr with either 0.5 µg/well of human IgGFab (ICN Biochemicals, Costa Mesa, CA, USA) or IgG-F(ab´) 2 fragments (Dianova).…”

Section: Methodsmentioning

confidence: 99%

Associations of blood levels of PCB, HCHS, and HCB with numbers of lymphocyte subpopulations, in vitro lymphocyte response, plasma cytokine levels, and immunoglobulin autoantibodies.

Daniel¹,

Huber²,

Bauer³

et al. 2001

Environ Health Perspect

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show abstract

“…Based on control measurements in 70 healthy individuals, > 15 nmol/l was considered abnormally high [18].…”

Section: Plasma Neopterinmentioning

confidence: 99%

Association of T cell dysfunction with the presence of IgG autoantibodies on CD4+ lymphocytes in haemophilia patients; results of a 10-year study

Daniel

Süsal

Weimer

et al. 1996

Clinical and Experimental Immunology

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HIV induces progressive dysfunction followed by numerical depletion of CD4+ lymphocytes. IgG autoantibodies and gp120‐containing immune complexes have been implicated in the pathogenesis of AIDS. We carried out a longitudinal study in 19 HIV– and 72 HIV+ haemophilia patients over a 10‐year period in order to investigate a possible relationship between the occurrence of autoantibodies and CD4+ lymphocyte changes. IgM, IgG, C3d and gp120 on the surface of CD4+ lymphocytes were determined in heparinized whole blood with flow cytometry and double‐fluorescence. The in vitro response of autoantibody‐coated cells was tested in cell cultures with concanavalin A (Con A), phytohaemagglutinin (PHA), pokeweed mitogen (PWM), anti‐CD3 MoAb or pooled allogeneic stimulator cells (MLC). After a 10‐year follow up, 12 of 71 HIV+ and 16 of 19 HIV– haemophilia patients showed no evidence of immunoglobulins on circulating CD4+ lymphocytes. HIV– haemophilia patients without autoantibodies had CD4+and CD8+ cell counts in the normal range (957 ± 642/μl and 636 ± 405/μl) and normal T cell responses in vitro (mean relative response (RR) ≥ 0.7). In contrast, HIV+ haemophilia patients showed immunological abnormalities which were associated with the autoantibody and immune complex load of CD4+ blood lymphocytes. HIV+ patients without autoantibodies had a mean CD4+ lymphocyte count of 372 ± 274/μl, a mean CD8+ lymphocyte count of 737 ± 435/μl, and normal T lymphocyte stimulation in vitro (mean RR ≥ 0.7). HIV+ patients with complement‐fixing IgM on CD4+ lymphocytes had somewhat lower CD4+ (255 ± 246/μl, P = NS) and CD8+ (706 ± 468/μl, P = NS) lymphocyte numbers, and also normal T lymphocyte stimulation (mean RR ≥ 0.7) in vitro. However, patients with complement‐fixing IgG autoantibodies showed a strong decrease of CD4+ (150 ± 146/μl, P < 0.02) and CD8+ (360 ± 300/μl, P < 0.02) lymphocytes and impaired CD4+ lymphocyte stimulation in vitro with a mean RR of 0.5 ± 0.5 for Con A (P = NS), 0.7 ± 0.8 for PHA (P < 0.03), 0.4 ± 0.4 for PWM (P = NS), 0.8 ± 1.2 for anti‐CD3 MoAb (P < 0.04) and 0.7 ± 1.0 for pooled allogeneic stimulator cells (P = 0.05). Patients with gp120‐containing immune complexes on CD4+ blood lymphocytes demonstrated strongly decreased CD4+ (25 ± 35/μl, P < 0.0001) and CD8+ (213 ± 212/μl, P < 0.006) lymphocyte counts as well as strongly impaired T lymphocyte responses in vitro upon stimulation with PHA (RR 0.2 ± 0.1, P < 0.02), PWM (RR 0.2 ± 0.2, P = 0.05), anti‐CD3 MoAb (RR 0.1 ± 0.1, P < 0.04), and allogeneic stimulator cells (RR 0.2 ± 0.1, P < 0.02). These data led us to speculate that autoantibody formation against CD4+ lymphocytes is an important mechanism in the pathogenesis of AIDS. We hypothesize that autoantibodies against circulating CD4+ lymphocytes inhibit CD4+ cell function, especially the release of cytokines, and induce CD4+ cell depletion. The reduction and dysfunction of CD4+ lymphocytes may be responsible for the CD8+ cell depletion observed in HIV+ patients.

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“…Comparable to the underlying results SAA showed a positive predictive value of 82% (22). Schaefer calculated a sensitivity of 86% for S-NEOP values, slightly lower than in the underlying study (23). In an analysis of 5 different parameters Ma~ galini described a high number of false negative results for s~IL-2R in plasma.…”

Section: Discussionmentioning

confidence: 67%

Neopterin, Serum Amyloid A, and Cytokine Monitoring After Renal Transplantation

et al. 1998

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SummaryA reliable and early diagnosis of viral infections and rejection episodes is a major goal of immunologic monitoring in transplantation . Soluble markers like the cytokines, neopterin or serum amyloid A are frequently recommended as diagnostic parameters. However they are not often used routinely in transplant medicine.The study investigates the diagnostic value of plasma (P), serum (S), and urine (U) levels of neopterin (S-/U-NEOP), serum amyloid A (SAA), tumor necrosis factor-a, ( P-/U -TNF-a), soluble interleukin-2 receptor (P-/U -sIL-2R), and interleukin-6 (U -IL-6) in transplant monitoring and describes an approach for their use in the clinical routine decision making.In 29 renal transplant patients blood and urine samples were collected daily during the posttransplant course on ward. The cytokines were measured by ELISAs, neopterin b y RIA, and SAA by immunonephelometry. Descriptive statistics, sensitivity and specificity, day of first significant parameter increase/decrease, receiver operating characteristic curves, and post-test probabilities were calculated for each parameter.12 acute rejection episodes were diagnosed. As rejection markers, S-NEOP and P-TNF-a had the highest sensitivity, U-IL-6 the highest specificity. 8 viral infections occurred. U-NEOP showed values higher than 1000 /-lmol!moICrea. It did not exceed this threshold in case of rejection episodes. SAA and U-IL-6 showed peak. levels during rejections but not during episodes of viral infections. Using the calculated likelihood ratio formulas the probability for the occurrence of an acute rejection could be estimated for the individual, daily parameter measurement. Adding the physician IS rating for rejection posttest probabilities were computed.Immunologic monitoring is possible in transplant medicine. Using daily measurements of serum amyloid A and neopterin facilitates the differential diagnosis of acute rejection episodes and viral infections. The likelihood ratio approach permits an application of the parameter monitoring in the clinical routine.

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Assessment of Plasma Neopterin in Clinical Kidney Transplantation

Cited by 77 publications

References 0 publications

Associations of blood levels of PCB, HCHS, and HCB with numbers of lymphocyte subpopulations, in vitro lymphocyte response, plasma cytokine levels, and immunoglobulin autoantibodies.

Associations of blood levels of PCB, HCHS, and HCB with numbers of lymphocyte subpopulations, in vitro lymphocyte response, plasma cytokine levels, and immunoglobulin autoantibodies.

Association of T cell dysfunction with the presence of IgG autoantibodies on CD4+ lymphocytes in haemophilia patients; results of a 10-year study

Neopterin, Serum Amyloid A, and Cytokine Monitoring After Renal Transplantation

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