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Gerhard Opelz

Publications and source records attributed to Gerhard Opelz.

62 records · Page 4Linked to original sources
PubMed2002

Soluble CD30 as a predictor of kidney graft outcome.

BACKGROUND: In the present study, we investigated whether the soluble form of CD30 (sCD30), a marker for T helper 2-type cytokine-producing T cells, is increased in sera of potential kidney graft recipients. We also investigated whether the pretransplantation serum sCD30 content is related to kidney graft survival. METHODS: Pretransplantation sera of 844 cadaver kidney recipients from three transplant centers in Germany were tested for serum sCD30 content using a commercially available ELISA kit. RESULTS: Kidney graft recipients showed a significantly higher serum sCD30 content than healthy controls (P<0.0001). High sCD30 serum content was associated with graft rejection. The 2-year graft survival rate in recipients with a high pretransplantation serum sCD30 was 68+/-6%, significantly lower than the 86+/-1% rate in recipients with a low sCD30 (P<0.0001). Importantly, high sCD30 was indicative of an increased risk of graft loss even in recipients without lymphocytotoxic alloantibodies. CONCLUSION: These data show that an elevated pretransplantation serum sCD30 reflects an immune state that is detrimental for kidney graft survival.

Adult↗
PubMed2002

Identification of highly responsive kidney transplant recipients using pretransplant soluble CD30.

The identification of high immunologic responders is desirable for the selection of appropriate immunosuppressive regimens. With the collaboration of 29 transplant centers in 15 countries, we investigated whether the pretransplant serum content of soluble CD30 (sCD30), a marker for the activation state of Th2-type cytokine producing T cells, is a useful predictor of kidney graft outcome. Pretransplant sera of 3899 cadaver kidney recipients were tested for serum sCD30 concentration using a commercially available enzyme-linked immunosorbent assay kit. Subsequent kidney graft survival was analyzed. The 5-yr graft survival rate in 901 recipients with a high pretransplant serum sCD30 (> or =100 U/ml) was 64 +/- 2%, significantly lower than the 75 +/- 1% rate in 2998 recipients with low sCD30 (<100 U/ml) (P < 0.0001). High sCD30 was associated primarily with graft loss and not with patient death. The sCD30 effect on graft survival was evident in first transplants as well as in retransplants, in presensitized patients with lymphocytotoxic antibodies as well as in nonsensitized patients, and in patients who received HLA well-matched kidneys as well as in patients who received poorly matched grafts. Recipients with a high pretransplant sCD30 needed significantly more rejection treatment after the first posttransplant year and continued to lose grafts at a higher rate during the 5-yr follow-up period, indicating that pretransplant sCD30 predicts not only the risk of acute rejection but also of chronic allograft nephropathy.

Adult↗
PubMed2002

The effect of donor gender on graft survival.

Differences in actuarial graft survival according to donor gender have been reported for renal allografts and for cardiac and hepatic allografts, but for the latter in small series with limited biostatistical power. Using the large database of the Collaborative Transplant Study (CTS), this study is an evaluation of graft survival according to donor and recipient gender for renal (n = 124,911), cardiac (n = 25,432), and hepatic (n = 16,410) transplants. Confounders, such as calendar year, geographical area, race, donor and recipient age, HLA mismatch, cold ischemia time, and others, as well as interaction terms were taken into consideration. Death-censored actuarial renal allograft survival from female compared with male donors was less in female recipients and even more so in male recipients. The donor gender-associated risk ratio for graft loss was 1.15 in female recipients and 1.22 in male recipients. The age-gender interaction term was statistically significant, the gender effect being more pronounced for younger (16 to 45 yr) compared with older (>45 yr) donors. Serum creatinine concentrations 1 yr after transplantation were also higher for recipients with kidney grafts coming from female donors irrespective of recipient gender. For first cardiac transplants, graft survival was inferior when the donor was female and the recipient male, but no statistical difference according to donor gender was demonstrable in female recipients. For first hepatic transplants overall, no significant differences according to donor gender were noted. The proportion of recipients who had treatment for rejection crisis during the first year was higher for male recipients of kidneys from female donors compared with male donors. No difference according to donor gender was demonstrable in female recipients. For cardiac and hepatic grafts, no significant effect of donor gender on the proportion of patients treated for rejection episodes was noted. The data show that adverse effects of female donor gender for different organs is much less uniform than reported in the past. An important confounder is donor age. A gender effect on graft survival is also observed for cardiac allografts. Therefore, in addition to potential "nephron underdosing," further pathomechanisms must play a role, possibly differences in immunogenicity according to donor gender.

Actuarial Analysis↗
PubMed2002

Immunosuppressive anti-immunoglobulin autoantibodies: specificity, gene structure and function in health and disease.

Anti-immunoglobulin autoantibodies (anti-Ig auto-Abs) are part of the physiological immune repertoire. Herein we focus on Abs directed against the F(ab')2 region of the Ig molecule. The vast majority of previously described anti-F(ab')2 auto-Abs were antiidiotypes. The antibodies we studied recognize epitopes located in the hinge region of IgG and in other conserved domains of F(ab')2. Gene structure analyses revealed germline gene identity of VL chains and 88% homology with the closest germline gene of VH chains. We present evidence for a B cell suppressive role of anti-Ig Abs and discuss the mechanism of suppression. Moreover, the role of anti-Ig auto-Abs in immunoregulation as well as in the pathogenesis of autoimmune and other diseases is discussed. There is substantial evidence indicating that anti-Ig auto-Abs are important immunoregulatory molecules.

Animals↗
PubMed2001

Impact of apolipoprotein(a) phenotypes on long-term renal transplant survival.

The long-term success of renal transplantation is limited because of chronic rejection (CR), which shows histologic parallels to atherosclerosis. Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerosis, but its role in CR has not been investigated. Plasma levels of Lp(a) are determined mainly by the inherited isoform (phenotype) of apolipoprotein(a) [apo(a)] and show an inverse correlation with the molecular weight of apo(a). Apo(a) isoforms were identified in frozen sera of 327 patients who received a renal transplant during 1982 to 1992. Long-term graft survival in recipients with high molecular weight (HMW) or low molecular weight (LMW) apo(a) phenotypes were compared retrospectively. Mean (95% confidence interval) transplant survival was 12.8 yr (range, 11.9 to 13.6 yr) in patients with HMW and 11.9 yr (range, 10.8 to 13.1 yr) in patients with LMW apo(a) phenotypes (P = 0.2065). In patients who were 35 yr or younger at the time of transplantation, mean transplant survival was more than 3 yr longer in recipients with HMW apo(a) phenotypes compared with those with LMW apo(a) phenotypes (13.2 yr [range, 12.1 to 14.4 yr] versus 9.9 yr (range, 8.5 to 11.5 yr); P = 0.0156). In a Cox's proportional hazards regression model, the presence of LMW phenotypes-but not gender, immunosuppression, or HLA mismatches-in young patients was associated with a statistically significant risk of CR (P = 0.0434). These retrospective data indicate that young renal transplant recipients with LMW apo(a) phenotypes have a significantly shorter long-term graft survival, regardless of the number of HLA mismatches, gender, or immunosuppressive treatment.

Adolescent↗
PubMedDate not supplied

Non-HLA transplantation immunity revealed by lymphocytotoxic antibodies.

BACKGROUND: The presence of panel-reactive antibodies (PRA) against HLA antigens before transplantation is associated with early rejection of kidney grafts from cadaver donors. Transplants from HLA-identical sibling donors do not provide a target for antibodies to HLA antigens and should therefore not be affected by PRA. METHODS: Data from the Collaborative Transplant Study were used to examine the influence of PRA on graft survival. Uncensored graft survival and death-censored graft survival were calculated, and the data were analysed by multivariate Cox's regression methods. FINDINGS: Among recipients of HLA-identical sibling transplants, 3001 patients with no PRA had significantly higher 10-year graft survival (72.4% [SE 1.1]) than 803 patients with 1-50% PRA (63.3% [2.5]; p=0.0006) or 244 patients with more than 50% PRA (55.5% [4.0]; p<0.0001). The effect of PRA became apparent after the first post-transplant year and was, therefore, strikingly different from the early steep decline in graft survival during the first year associated with PRA in recipients of cadaver kidneys. We could not discern whether graft loss was a direct effect of non-HLA humoral sensitisation or whether PRA served as an indicator of heightened immunity against non-HLA transplantation antigens. INTERPRETATION: PRA reactivity is strongly associated with long-term graft loss in kidney transplants from HLA-identical sibling donors. RELEVANCE TO PRACTICE: Our findings suggest that non-HLA immunity has a much stronger role in clinical transplantation than previously thought. In contrast to immunity against HLA mediated by antibodies present before transplantation, which leads to early acute graft rejection, non-HLA immunity is associated with chronic graft loss. The possibility of identifying recipients at increased risk of late graft loss before transplantation could be used to devise specific immunosuppressive strategies for these patients.

Antilymphocyte Serum↗
PubMedDate not supplied

Associations of dichlorodiphenyltrichloroethane (DDT) 4.4 and dichlorodiphenyldichloroethylene (DDE) 4.4 blood levels with plasma IL-4.

DDT (dichlorodiphenyltrichloroethane) reportedly induces cancer in animals, mimics estrogen activity, induces antiandrogen effects, and impairs Natural Killer (NK) cells and T lymphocyte responses. In this study, the authors attempted to determine associations of DDT, dichlorodiphenyldichloroethylene (DDE), and dichlorodiphenyldichloroethane (DDD) blood levels with several immune parameters in patients occupationally exposed to insecticides. The study subjects were 49 patients who worked as farmers or farmhands in the former German Democratic Republic and who had been occupationally exposed to insecticides for at least 6 mo; 80% of them had been exposed for more than 20 yr. Blood levels of DDT, DDE, DDD, 2,3,4,5,6-pentachlorophenol (PCP), polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), and gamma-hexachlorocyclohexanes (HCHs) were determined, and blood lymphocyte subpopulations, in vitro responses to mitogens or pooled allogeneic stimulator cells, plasma neopterin, and cytokine and soluble cytokine receptor levels were studied. The majority of patients were contaminated with more than 1 chemical--most commonly DDE, PCBs, and HCB. Linear-regression analysis showed that interleukin-4 (IL-4) plasma levels were associated with plasma levels of DDT 4.4 (p = .0001) and DDE 4.4 (p = .001). The data in this study suggest that PCBs, PCP, HCB, HCHs, DDE, and DDD suppress TH1 cytokines, such as IL-2 and interferon-gamma (IFN-gamma), and induce TH2 cytokines, such as IL-4. The authors hypothesized that clinical symptoms, such as the frequent infections reported by many patients, could be a consequence of these immunological abnormalities.

Adult↗