Search PubMed⌕ Search

Biomedical subjects

W Weimar

Publications and source records attributed to W Weimar.

At least 73 records · Page 4Linked to original sources
PubMed2001

Increased numbers of circulating donor-specific T helper lymphocytes after human heart valve transplantation.

Implantation of cryopreserved human donor heart valves for either congenital or acquired cardiac disease has been performed since the last three decades. Although the clinical outcome is good, long-term valve degeneration resulting in dysfunction has been observed. A specific immunological response of the recipient against the allograft has been proposed as one of the factors involved in this process. Helper T lymphocytes play an important intermediate role in cellular and humoral immune response. Increasing numbers of circulating donor-specific helper T lymphocytes precursors (HTLp) correlate with graft rejection after organ transplantation. To investigate whether cryopreserved human donor heart valves are able to induce a donor-specific T helper response, we monitored the HTLp frequencies (HTLpf) in peripheral blood samples of 13 patients after valve allograft transplantation by use of a limiting dilution assay followed by an interleukin-2 bioassay. Prior to transplantation, HTLpf specific for donor and third-party antigens showed individual baseline levels. After allografting, the antidonor frequencies significantly increased in 11 of the 13 patients (P = 0.02). This was not found for stimulation with third-party spleen cells (P = 0.68), which indicates a donor-specific response. Maximal donor-specific HTLpf were already found at 1--2 months after operation. Valve allograft transplantation induces an increase in the numbers of donor-specific HTLp in peripheral blood of the patients. Analogous to organ transplantation, these HTLp may play a crucial role in events that lead to valve damage. Therefore, monitoring of HTLp in peripheral blood samples might be informative for donor valve degeneration (rejection) and subsequently valve allograft failure.

Adult↗
PubMed2001

T cells activate the tumor necrosis factor-alpha system during hemodialysis, resulting in tachyphylaxis.

BACKGROUND: The immunosuppressive state of hemodialysis (HD) patients is accompanied by activation of antigen-presenting cell-derived cytokines, for example, tumor necrosis factor-alpha (TNF-alpha), which are required for T-cell activation. To test whether an activated TNF-alpha system results in impaired T-cell response in these patients, we analyzed parameters of their antigen-presenting cell (APC) function (for example, TNF-alpha system) and T-cell function [for example, interleukin-2 (IL-2) system]. METHODS: By quantitative flow cytometry, the expression of the TNF-receptor 2 (TNF-R2 = CD120b) and the alpha and beta chain of the IL-2 receptor (IL-2R; CD25, CD122) was measured. Using reverse transcriptase-polymerase chain reaction, the mRNA for TNF-alpha, IL-2, and IL-2R were determined. Phyto-hemagglutinin (PHA)- and IL-2-stimulated proliferation and cytokine production were measured. Biological activity of soluble receptors was measured by adding recombinant cytokines to the patient's plasma. RESULTS: CD120b expression was significantly increased in HD patients, whereas CD25 and CD122 was comparable to controls. In contrast to mRNA for IL-2 and IL-2R, mRNA for TNF-alpha was increased in HD. This resulted in significantly increased TNF-alpha levels in HD patients. In peripheral blood of HD patients, high levels of soluble TNF-R (R1 and R2) and IL-2R were found. These receptors were capable of binding 40% of added TNF-alpha and 55% of added IL-2. PHA-induced TNF-alpha production by T cells from HD patients was significantly lower, while their PHA-stimulated IL-2 production and proliferation capacity by T cells were comparable to controls. CONCLUSIONS: We conclude that although the TNF-alpha system is activated during HD, the TNF-alpha production of T cells is impaired, suggesting that tachyphylaxis of T cells occurs for TNF-alpha, as their proliferative capacity and IL-2 production capacity do not imply an intrinsic T-cell defect.

Aged↗
PubMed2001

Quantitative flow cytometry shows activation of the TNF-alpha system but not of the IL-2 system at the single cell level in renal replacement therapy.

BACKGROUND: Immunological dysfunction in patients on haemodialysis may be related to imbalanced cytokine systems, such as tumour necrosis factor (TNF)-alpha and interleukin (IL)-2. Despite activation of these systems, haemodialysis patients show high susceptibility for infections and malignancies, and have a poor immunological reaction to T-cell-dependent antigens, like hepatitis B vaccination. In this study we have determined the activation status of the two different cytokine systems, at the single cell level, using quantitative flow cytometry. METHODS: Using fluorescein isothiocyanate- or phycoerythrin-conjugated antibodies directed against TNF-R2 (CD120b), IL-2Ralpha (CD25) and IL-2Rbeta (CD122), we measured the expression of these receptors at the single cell level in order to determine the level of activation of monocytes and T-lymphocytes. RESULTS: Significantly higher expression of the TNF-alpha receptor, TNF-R2, was present on both monocytes and T-lymphocytes in patients on renal replacement therapy (RRT) compared with pre-dialysis chronic renal failure (CRF) patients and controls, indicating activation of the TNF-alpha system. In contrast, IL-2R expression was comparable in all groups studied, which may reflect a non-activated state of the IL-2 system. CONCLUSIONS: The present study illustrates an activated state of the TNF-alpha system in patients on RRT, at the single cell level, while the IL-2 system seems to be unaffected. These findings support the hypothesis that the interaction between the TNF-alpha and IL-2 cytokine systems is disturbed.

Adult↗
PubMed2001

Long-term graft survival after urological complications of 695 kidney transplantations.

PURPOSE: We ascertain the incidence, management and long-term outcome of early urological complications requiring surgical exploration in kidney transplantation. MATERIALS AND METHODS: Data of 695 consecutive kidney transplantations performed between January 1985 and January 1997 were assessed in regard to urological complications that occurred within 1 year after transplant. A computerized database was used to analyze graft recipient characteristics, the implantation procedure, complications and outcome in select patients and all those who underwent transplant during the same period. In the noncomplication group sufficient data for evaluation was available for 556 patients. We performed the Cox proportional hazards analysis with overall graft failure, graft failure or death as end points of observation. RESULTS: Overall, 42 (6.0%) patients required revision of vesicoureteral anastomosis. Complications were identified after a median of 6 days (range 0 to 135). The primary reconstruction technique was extravesical in 64% and transvesical in 33% of patients, including 1 that involved ureteral Bricker anastomosis. Obstruction and/or leakage at vesicoureteral anastomosis accounted for 69% of urological complications. Revision was performed with a number of different reconstruction techniques. A second revision was required in 16.7%. Mean followup after primary transplant was 9.1 years (range 3.2 to 15). Multivariate analysis showed that surgical treatment of urological complication during year 1 after kidney transplantation did not increase the risk of overall graft failure, graft failure or death. CONCLUSIONS: Our results indicate that long-term graft survival is not affected by a surgically treated urological complication.

Adult↗
PubMed2001

Increase in blood volume during dialysis without ultrafiltration.

Combined dialysis and ultrafiltration leads to more frequent episodes of hypotension than isolated ultrafiltration. It has been suggested that decreased plasma volume preservation could be responsible for this phenomenon. The present study evaluates the effects of diffusive dialysis on the changes in relative blood volume (RBV). Six stable hemodialysis patients, without the need of ultrafiltration, were studied during 10 sessions of diffusive dialysis (bicarbonate) lasting 4 h. RBV was monitored continuously by measurement of hematocrit. During the 1st and 2nd h RBV increased by 2.4+/-1.4 and 2.5+/-0.8% respectively, returning to baseline levels at the end of dialysis. No changes in blood pressure or heart rate were noted. We conclude that during diffusive dialysis without ultrafiltration RBV is increased. A decrease in vascular resistance, or changes in regional blood distribution could explain these findings.

Adult↗
PubMed2000

Addition of isradipine (Lomir) results in a better renal function after kidney transplantation: a double-blind, randomized, placebo-controlled, multi-center study.

BACKGROUND: After successful kidney transplantation patients may suffer from the adverse effects due to the use of calcineurin inhibitors. Calcium channel blockers are effective in the treatment of hypertension and may ameliorate cyclosporine- (CsA) induced impairment of renal function after kidney transplantation. Calcium channel blockers may also modulate the immune-system which may result in reduction of acute rejection episodes. PATIENTS AND METHODS: From June 1995 till 1997 the effect of isradipine (Lomir) on renal function, incidence and severity of delayed graft function (DGF), and acute rejection after kidney transplantation, was studied in 210 renal transplant recipients, who were randomized to receive isradipine (n=98) or placebo (n=112) after renal transplantation in a double-blind fashion. RESULTS: In the isradipine group renal function was significantly better at 3 and 12 months (P=0.002 and P=0.021) compared with the placebo group. DGF was present in both groups: isradipine: (28+6)/98 (35%); placebo: (35+9)/112 (40%), P=0.57. Severity of DGF was comparable in both groups (isradipine: 9.1+/-8.7 vs. placebo: 9.3+/-8.1 days). No statistical difference was found in incidence or severity of biopsy-proven acute rejection [isradipine: (42+6)/98 (49%) versus placebo: (46+9)/112 (49%), P=1.00]. Renal vein thrombosis was observed in eight patients. This proved to be associated with the route of administration of the study medication [6/45 (13%) on i.v. medication versus 2/165 (1%) on oral medication, P<0.001]. CONCLUSIONS: Addition of isradipine results in a better renal function after kidney transplantation, without effect on incidence or severity of DGF or acute rejection.

Adult↗
PubMed2000

Donor-specific T-cell reactivity identifies kidney transplant patients in whom immunosuppressive therapy can be safely reduced.

BACKGROUND: To reduce the side effects of long-term immunosuppressive therapy, stable renal transplant patients were routinely converted from cyclosporine to either azathioprine or mycophenolate mofetil. Thereafter, the azathioprine and mycophenolate mofetil dose was reduced to 75% at 4 months and to 50% at 8 months after conversion. We questioned whether the T-cell reactivity before conversion was able to predict which patients could be safely converted and tapered in their immunosuppressive load, while remaining free from acute rejection. METHODS: Before conversion, the T-cell reactivity of peripheral blood mononuclear cells against donor and third-party spleen cells were tested in mixed lymphocyte cultures. We measured the frequency of donor and third-party reactive helper T-lymphocyte (HTLpf) and cytotoxic T-lymphocyte (CTLpf) precursors and their avidity for HLA class I antigens using limiting dilution analysis. Peripheral blood mononuclear cells were also stimulated with tetanus toxoid to test the general immune response. RESULTS: The tetanus toxoid response, reactivity to donor and third-party cells as measured in mixed lymphocyte cultures and HTLpf, and the avidity of cytotoxic T-lymphocyte precursors were not predictive for the development of acute rejection. However, significant differences were found in donor-specific CTLpf before conversion, between patients with and without acute rejection after conversion in immunosuppression. The donor-specific CTLpf was significantly lower in patients without compared to those with acute rejection (P=0.01). Additionally, when no CTLpf was detectable before conversion, acute rejection did not occur after conversion. Acute rejection was only diagnosed in patients with detectable CTLpf before conversion. CONCLUSION: The number of donor-specific cytotoxic T-lymphocytes identifies patients in whom the immunosuppressive load can be safely reduced.

Acute Disease↗
PubMed2000

Randomized study on the conversion of treatment with cyclosporine to azathioprine or mycophenolate mofetil followed by dose reduction.

BACKGROUND: The introduction of cyclosporine (CsA) in kidney transplantation has improved early graft survival. However, its long-term use is associated with impairment of renal function and increased cardiovascular risk factors. To avoid CsA-related long-term adverse effects, patients were converted to either azathioprine (AZA) or mycophenolate mofetil (MMF) 1 year after transplantation. METHODS: Between September 1995 and January 1997, 64 stable renal transplant recipients on CsA and prednisone treatment were included in a prospective, randomized study. Patients were randomized for conversion of CsA to 2 mg/kg AZA (n=30) or 1 g of MMF twice daily (n=34). All patients remained on low-dose steroids. To decrease the total immunosuppressive load, a dose reduction in MMF and AZA was performed at 4 and again at 8 months after conversion. Mycophenolic acid trough levels were measured at regular intervals. RESULTS: After conversion, a decrease in serum creatinine was found for both groups: for MMF, 132 to 109 micromol/L (P=0.016); and for AZA, 123 to 112 micromol/L (P<0.0001). After conversion, more acute rejections occurred in the AZA group (11/30) compared to the MMF group (4/34) (P=0.04). Dose reduction of MMF to 500 mg twice daily and of AZA to 1.0 mg/kg elicited three rejections in both groups. The incidence of side effects and infections were similar. CONCLUSION: Discontinuation of CsA spared renal function. In patients converted to MMF significantly less rejections occurred compared to patients converted to AZA. Furthermore, dose reduction of both AZA and MMF is possible in the majority (72%) of the patients.

Adult↗
PubMed2000

Cholesterol as an independent predictor of outcome after renal transplantation.

BACKGROUND: The debate on the role of high serum cholesterol levels in cardiovascular disease or chronic vascular rejection in kidney-transplanted patients has not yet been settled. METHODS: We studied the influence of serum cholesterol at 1 year after transplantation on the failure risk in all 676 kidney graft recipients who survived with a functioning graft. Other variables included in this analysis were donor/recipient age and gender, original disease, race, number of HLA-A and -B mismatches, previous transplants, postmortal or living-related transplantation, and transplantation year. At 1 year after transplantation, we included: serum cholesterol, serum creatinine, proteinuria, and hypertension. RESULTS: In the Cox proportional hazards analysis, serum cholesterol at 1 year after transplantation turned out to be an important, independent variable influencing all end points (adjusted for all other variables in the model). The influence on graft failure censored for death was log-linear, and there was interaction with serum creatinine at 1 year. The adverse effect of elevated serum cholesterol levels on the graft failure rate decreased with increasing serum creatinine levels. The influence of serum cholesterol on the rate ratio (RR) for patient failure was linear too, and here there was interaction with recipient age. The negative influence of serum cholesterol on the RR for patient failure decreased with increasing recipient age. The risk for over-all graft failure was influenced by increasing serum cholesterol levels, and there was interaction with recipient age. Because recipient age had interaction with donor age and serum creatinine, the influence of all four variables together on the RR was estimated. It is shown that whereas the RR for over-all graft failure in young recipients of a renal transplant increases significantly with higher cholesterol levels, there is very little influence on the RR of elderly recipients. The risk increases proportionally with increasing serum creatinine levels. CONCLUSION: Serum cholesterol levels have an independent influence on graft, patient, and over-all graft failure.

Adult↗
PubMed2000

Functional responses of T cells blocked by anti-CD25 antibody therapy during cardiac rejection.

BACKGROUND: Despite anti-CD25 (interleukin [IL]-2 receptor alpha chain) monoclonal antibody (mAb) therapy, rejection can still occur. T-cell activation through the IL-2 receptor beta and gamma chains by IL-2 or other growth factors may contribute to this rejection. Recently, we have demonstrated that the T-cell growth factor IL-15 was abundantly present in rejecting cardiac grafts during anti-CD25 mAb treatment. METHODS: To test whether IL-2- and IL-15-responsive T cells play an active role in rejection during anti-CD25 mAb therapy, we measured the frequency of IL-2- and IL-15-proliferative T cells in peripheral blood from treated patients during rejection (n=12). Measurements were made by limiting dilution analysis in the absence and presence of extra in vitro-added mouse anti-human CD25 mAb. RESULTS: In the absence of anti-CD25 mAb, the frequencies of peripheral T cells responding to recombinant human (rh)IL-2 and rhIL-15 from patients were lower than those measured in samples of healthy controls (n=7): median of IL-2-responding T cells 78 per 10(6) (range 31-210 per 10(6)) vs. 154 per 10(6) (122-484 per 10(6), P=0.008) and median of IL-15-responding T cells 62 per 10(6) (range 19-207 per 10(6)) vs. 129 per 10(6) (range 79-192 per 10(6), P=0.02), respectively. In the presence of extra in vitro-added anti-CD25 mAb, frequencies of IL-2-responding T cells from patients significantly decreased, although a considerable number of T cells still proliferated on rhIL-2 (median 85%, range 46-100%). In contrast, the frequencies of IL-15 T cells still responding remained stable (median 2%, range 0-50%, P<0.001). CONCLUSIONS: Treatment with anti-CD25 mAbs cannot provide complete suppression of T-cell function because significant numbers of IL-2- and IL-15-responsive T cells remain present in the peripheral blood of allograft recipients during anti-CD25 mAb treatment.

Animals↗
PubMed2000

The influence of cholesterol on mortality after transplantation is age dependent.

There is still no consensus on the treatment of elevated serum cholesterol in patients with a renal transplant. In the general population treatment is age dependent. We studied the influence of serum cholesterol 1 year after transplantation in all 676 recipients of a kidney graft transplanted in Rotterdam that survived and functioned for at least 1 year. The other variables included in this analysis are: donor and recipient age and gender, original disease, race, number of HLA A and B mismatches, number of previous transplantations, postmortal or living related transplantation and transplantation year. At 1 year after transplantation the following variables were included: serum cholesterol, serum creatinine, proteinuria and hypertension. In the Cox proportional hazards analysis, serum cholesterol at 1 year after transplantation turned out to be an important, independent variable influencing patient failure. The influence was linear but there was interaction with recipient age. The negative influence of serum cholesterol on the RR for patient failure decreased with increasing recipient age. For example, the proportional increase in RR of a 20-year-old with a serum cholesterol of 12 mmol/l compared with that of a cholesterol of a patient with serum cholesterol of 6 mmol/l was 6. In a 60-year-old with a cholesterol of 12 mmol/l the proportional increase in RR was only 1.2 compared with a contemporary with a cholesterol of 6 mmol/l. Serum cholesterol levels have an independent influence on patient failure. The RR is influenced by recipient age, so that the negative effect of increasing cholesterol levels in the elderly is overruled by the RR of age and disappears.

Adult↗
PubMed2000

Quantitative flow cytometry to measure the TNF-alpha and IL-2 system after heart transplantation.

After heart transplantation a high incidence of infections and malignancies is found. Not only immunosuppression, but also intrinsic cytokine systems with some unbalance, e. g. TNF-alpha and IL-2, can result in impaired immune competence and may have a role in these complications. The aim of this study was to assess the activity of the TNF-alpha and IL-2 systems after heart transplantation. In peripheral blood we measured expression of activation markers of TNF-alpha (TNF-R2) and IL-2 (IL-2R alpha, IL-2R beta-chain) on monocytes and lymphocytes using quantitative flow-cytometric analysis. TNF-R2 expression was significantly enhanced on monocytes and lymphocytes in patients after heart transplantation, while the expression of IL-2R alpha and IL-2R beta was not elevated. Increased TNF-R2 expression in peripheral blood after heart transplantation reflects an activated TNF-alpha system, leading to high levels of active sTNF-R, which impairs TNF-alpha bioavailibility and consequently leads to immune incompetence.

Adult↗
PubMed2000

Mycophenolic acid trough levels after kidney transplantation in a cyclosporine-free protocol.

Twenty-seven stable kidney transplant recipients treated with cyclosporine and prednisone were converted to mycophenolate mofetil (MMF) and prednisone 1 year after transplantation. After conversion the patients were treated with a standard daily dose of 1 g MMF b.i.d. and 10 mg prednisone for 4 months. Thereafter, two MMF dose reductions were performed with a 4-month interval. Mycophenolic acid (MPA) trough levels were measured at regular intervals. A relation was found between MPA trough levels and MMF dose. The median MPA trough level for patients treated with 1 g MMF b.i.d. was 4.3 microg/ml (0.95-15.5) and 3.0 microg/ml (0.73-7.8) for patients treated with 750 mg b.i.d. (P = 0.0002). The MPA trough levels further decreased from 3.0 to 2.3 microg/ml (0.6-6.63) in patients treated with 500 mg MMF b.i.d. (P = 0.01). Dose reduction of MMF from 1 g to 750 mg b.i.d. could be performed without acute rejections. A further dose reduction to 500 mg b.i.d. elicited 3 rejections. Patients experiencing an acute rejection had a median MPA trough level of 2.3 microg/ml (1.26-3.38) compared to 3.8 microg/ml (1.48-6.52) in patients without an acute rejection (P = 0.25). We conclude that there is a significant relation between MPA trough levels and MMF dose. MPA trough levels were not predictive of rejection in the present study.

Area Under Curve↗
PubMed2000

Heart valve dysfunction resulting from cellular rejection in a novel heterotopic transplantation rat model.

Structural failure of heart valve allografts may be related to technical factors or immunological reactions. To circumvent nonimmunological factors a new rat implantation model was developed to study whether alloreactivity results in histopathological changes and valve dysfunction. Syngeneic (WAG-WAG, DA-DA) and allogeneic (WAG-BN, WAG-DA) transplantation was carried out using this new technique, and the function of explanted valves was assessed 21 days later by retrograde competence testing. Additionally, grafts were examined using standard histological and immunohistochemical techniques. There was no leakage during retrograde injection in nine of tem syngeneic and two of ten allogeneic grafts. Microscopically, syngeneic valves appeared normal without fibrosis or intimal thickening, although CD8+ lymphocytes and macrophages were found in necrotic myocardial rim and adventitia. In contrast, allogeneic valves were deformed and noncellular, with extensive infiltration of CD4+, CD8+ and CD68+ cells in adventitia and media. Absence of fibrosis and intimal thickening in syngeneic transplanted valves indicated circumvention of nonimmunological factors. Allogeneic valve transplantation induces cellular infiltration in the graft with subsequent graft failure.

Animals↗
PubMed2000

Mycophenolate mofetil, Cellcept, a new immunosuppressive drug with great potential in internal medicine.

Mycophenolate mofetil is a new immunosuppressive drug, exhibiting its effect through inhibition of proliferation of T- and B-lymphocytes. Superior efficacy of mycophenolate mofetil compared to azathioprine, in combination with cyclosporine and prednisone, in the prevention of acute rejection in organ transplantation has made mycophenolate mofetil one of the standard immunosuppressive drugs after transplantation. Mycophenolate mofetil also is an interesting candidate drug for many other, mainly auto-immune mediated diseases. The use of mycophenolate mofetil in several of these diseases is discussed. The definitive place of mycophenolate mofetil will depend on the results of randomised trials currently under way.

Autoimmune Diseases↗
PubMed2000

Modulation of the T cell receptor beta chain repertoire after heart transplantation.

BACKGROUND: In a previous study it was shown that pre-transplant blood transfusion was associated with a better clinical outcome after heart transplantation (HTx). In this study the effect of heart transplantation (HTx) on the T cell receptor V beta chain (TCRVbeta) repertoire was investigated. Therefore, we analyzed the TCRVbeta repertoire of patients after HTx to see whether a correlation with clinical outcome could be observed. METHODS: Patients were analyzed at four different time points: pre-HTx, less than 1 month post-Htx, between 1 month and 2.5 month post-Htx and more than 2.5 months post-HTx. CD4+ and CD8+ T cells were purified from patient peripheral blood mononuclear cells (PBMC). TCR beta chain usage was analyzed semiquantitatively by Southern blot analysis. RESULTS: HTx affected the TCRVbeta repertoire in both the CD4+ and CD8+ T cell compartments in all patients. Changes in the TCRVbeta repertoire were most pronounced within the CD8+ T cell subset. Interestingly, one patient showed modulation in TCRVbeta chain usage predominantly in the CD4+ T cell compartment. CONCLUSIONS: Modulation of TCRVbeta chain usage was detected in all patients analyzed. No clear-cut relation was observed between TCRVbeta modulation after transplantation and clinical outcome. In some cases modulations appeared to concur with observed immunological events (clinically and/or in-vitro).

HLA-DR Antigens↗
PubMed2000

Donor-derived soluble HLA plasma levels can not be used to monitor graft rejection in heart transplant recipients.

OBJECTIVE: Increased levels of both donor- and recipient-derived HLA class I molecules (sHLA-I) can be found in serum or plasma of transplanted patients during rejection. Earlier data indicate that levels of donor-derived sHLA-I (dsHLA-I) correlate better with graft rejection than total sHLA Class I (Zavazava N, Kraatz E, Gassel AM, Muller-Ruchholtz W. Plasma MHC class I expression in cardiac graft patients: donor-specific soluble antigen in a pre-sensitized graft patient. Transplant Proc 1991;23:2258-2260; Claas FHJ, Jankowska-Gan E, DeVito LD, et al. Monitoring of heart transplant rejection using a donor-specific soluble HLA class I ELISA. Hum Immunol 1993;37:121). Therefore, quantifying donor-derived soluble counterparts of HLA Class I (sHLA-I) in the plasma of the recipient may offer a new possibility for non-invasive monitoring of rejection after organ transplantation. METHODS: In an extended study with 34 heart transplant recipients, we used sHLA-I specific ELISAs to monitor donor-derived soluble sHLA-A2, -A3, -A9, -B7, -B12 and B51. RESULTS: The assays were sensitive enough to detect dsHLA Class I in plasma of the recipients. However, the levels of sHLA were not found to be a useful tool for monitoring rejection. Rejection was often associated with low levels of donor sHLA. The recent finding that antibodies can inhibit the detection of sHLA molecules might explain this discrepancy. In order to test this hypothesis, patient sera were screened for the presence of anti-HLA antibodies and the results were related to the donor-derived sHLA levels. Only in four out of 34 patients HLA Class I specific antibodies could explain the low sHLA levels during rejection. CONCLUSIONS: In heart transplantation increased donor-derived sHLA levels are not a suitable marker for rejection and that antibody formation can not explain these results. Therefore, monitoring rejection episodes on the basis of donor-derived soluble HLA molecules is not a realistic approach to decrease the number of biopsies after heart transplantation.

Animals↗