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G Opelz

Publications and source records attributed to G Opelz.

At least 91 records · Page 5Linked to original sources
PubMed1997

The antigen-binding domain of a human IgG-anti-F(ab')2 autoantibody.

Recent studies revealed an immunoregulatory role of natural IgG-anti-F(ab')2 antibodies in both healthy individuals and patients with certain diseases. The implication of anti-F(ab')2 antibodies in the pathogenesis of diseases prompted us to study the gene segment structure of their antigen-binding domains and their binding characteristics. cDNA was prepared from the lymphocytes of a patient with a high IgG-anti-F(ab')2 serum titer. Variable heavy and light gene segments were amplified by PCR and inserted into a phagemid surface expression vector. Single-chain antibodies displayed on the phage surface were screened for binding to F(ab')2 fragments. The subsequent analysis of 95 single clones demonstrated that they all bound specifically to F(ab')2. Sequence analyses of 12 clones showed that 11 were identical and 1 contained a silent point mutation in the heavy chain and three amino acid exchanges in the light chain. The heavy chains belonged to the V(H)3 and the light chains to the V(kappa)2 gene family. The 11 identical light-chain genes were completely homologous to a germ-line sequence (DPK-15). Binding assays showed that the single-chain antibodies bind to F(ab')2, but not to Fab, Fc, or intact IgG. This binding pattern was confirmed by surface plasmon resonance studies, which revealed a relatively high affinity (Ka = 2.8 x 10(7) M(-1)). The strong binding capacity was further demonstrated by competitive inhibition of the serum anti-IgG antibody's interaction with antigen. The present study defines for the first time to our knowledge the gene segment structure of the antigen-binding domain of two human IgG-anti-F(ab')2 autoantibody clones and describes the binding kinetics of the purified monomeric fragments.

Amino Acid Sequence↗
PubMed1997

Analysis of HLA-DR split-specificity matching in cadaver kidney transplantation: a report of the Collaborative Transplant Study.

The influence of mismatches for HLA-DR "split" specificities was investigated in more than 8000 cadaver kidney transplants. HLA-DR typing was performed using DNA methodology. Among first transplants, mismatches defined by HLA-DR split specificities did not have a deleterious influence. Among retransplants, however, graft survival was significantly decreased if a mismatch was defined, considering split specificities in patients with no mismatch according to the "broad" definition (P=0.04) and also in grafts with two split mismatches, which showed only one mismatch according to the broad definition (P=0.03). Moreover, consideration of further "subsplit" specificities resulted in clinically relevant mismatches only among retransplants. These data indicate that the recognition of HLA-DR split specificity mismatches is fundamentally different in primary and regraft recipients. The results imply that recipients and donors of kidney retransplants should be typed for HLA-DR split specificities and that these specificities should be considered for organ allocation.

Alleles↗
PubMed1997

Anti-MIP-1alpha and anti-RANTES antibodies: new allies of HIV-1?

The human immunodeficiency virus type 1 was recently found to use several chemokine receptors in addition to the CD4 molecule for attachment to, and fusion with, CD4+ cells. The interaction between macrophage-tropic HIV-1 strains and one of these chemokine receptors, CCR5, was shown to involve the V3-loop of the viral envelope glycoprotein gp120. Physiological ligands of CCR5, namely the beta-chemokines MIP-1alpha, MIP-1beta, and RANTES, were found to competitively inhibit the V3-loop-CCR5 interaction. We therefore hypothesized that the V3-loop of gp120 of macrophage-tropic HIV-1 may share a binding site on CCR5 with MIP-1alpha, MIP-1beta, and RANTES and that the V3-loop therefore might have some homology with these beta-chemokines. In the present study, we could demonstrate that affinity purified anti-V3-loop antibodies isolated from serum of an HIV-1-infected patient bound to MIP-1alpha and RANTES. Furthermore, sera of HIV-infected hemophilia patients without AIDS or ARC had significantly higher anti-MIP-1alpha and anti-RANTES antibody activities than sera of HIV-infected hemophilia patients with AIDS. We speculate that the higher activities of anti-MIP-1alpha and anti-RANTES antibodies in asymptomatic HIV-1 infected individuals might be due to a cross-reaction of beta-chemokines with anti-V3-loop antibodies raised against gp120 of macrophage-tropic HIV-1 strains, known to be prevailing in the asymptomatic stage of HIV infection. Such anti-chemokine antibodies may play a deleterious role in the pathogenesis of AIDS by reducing the chemokines' potential to inhibit HIV-1 entry into CD4+ cells.

AIDS-Related Complex↗
PubMed1997

HLA-DR7 predicts the response to alkylating agents in steroid-sensitive nephrotic syndrome.

There is a lack of reliable predictors of the response to alkylating agents in children with idiopathic nephrotic syndrome (NS). HLA-DR7 is strongly associated with the frequency of relapses in steroid-sensitive NS before cytostatic therapy. We therefore examined retrospectively the time to the first relapse and the incidence of subsequent relapses in 54 HLA-typed children with frequently relapsing NS, after treatment with cyclophosphamide (n = 49) or chlorambucil (n = 5) for 8 or 12 weeks; 38 patients were HLA-DR7 positive and 16 negative with 80% in both groups being steroid dependent. HLA typing was performed using serological or DNA typing methods. Renal biopsy showed minimal glomerular changes. A lower proportion of HLA-DR7 positive than negative patients remained in remission after 3 years (36% vs. 81%, P < 0.02) and 5 years (36% vs. 72%, P < 0.03). In the first 3 years after cytostatic therapy the mean number of prednisone-treated relapses was 1.3/patient per year in HLA-DR7-positive patients compared with 0.4 in negative patients (P < 0.025). There was no statistically significant difference in the proportion of relapse-free patients with and without steroid dependency. The HLA status predicts the response of NS patients to alkylating agents better than the rate of previous relapses.

Adolescent↗
PubMed1997

Oligotyping for HLA-DQA, -DQB, and -DPB in idiopathic nephrotic syndrome.

Associations of human leukocyte antigens (HLA) with the idiopathic nephrotic syndrome (NS) have mainly been described for alleles of the HLA-DR locus. In the present study the polymorphism of HLA-DQ and -DP at the molecular level was investigated in 167 children with NS (129 steroid-sensitive) using the polymerase chain reaction and sequence-specific oligonucleotides in a French and a German cohort. HLA-DR typing was also performed by classical serology. In steroid-sensitive patients we observed an increased frequency of the alleles HLA-DQA1*0201 and -DQB1*0201 in both populations with relative risks ranging from 3.8 to 8.5 (Pb < 0.01 to Pb < 0.00001 after Bonferoni's correction). In contrast, the frequency of HLA-DQA1*0102 and DQB1*0602 was significantly decreased. In children with frequent relapses the HLA associations were generally more pronounced than in those with infrequent or no relapses. Applying logistic regression analysis, a nephrotic child bearing DQA1*0201 or DR7 was five times more likely to be in the steroid-sensitive group of patients than in the steroid-resistant group compared with nephrotic children not bearing one of these alleles. These HLA alleles therefore seem to be useful indicators of a steroid-sensitive frequently relapsing course of NS. No associations with DPB alleles were observed, which narrows the region genetically involved in the disease susceptibility to the DR-DQ region. Steroid-resistant NS was not associated with HLA.

Adolescent↗
PubMed1997

Transplantation in the elderly: a review.

PURPOSE: 1. To review current knowledge about patient and graft survival, complication rates, patient selection and management protocols in patients aged 60 years or more with a renal transplant. 2. To review the advantages and disadvantages of cadaveric organ retrieval from older donors. DATA SOURCES: Evidence was obtained from published articles identified using a MEDLINE search from 1976 to 1996; expert opinion and citations from previous review articles. RESULTS: Survival rates have improved with time and now range from 54 to 75% 5-year patient survival and 52-74% 5-year graft survival. The most common reason for graft loss is patient death as both acute and chronic rejection is less commonly seen in older patients. Censored graft survival (if death with a functioning graft is treated as censored data) is higher in elderly patients compared to younger ESRD patients. Based on cohort data from an administrative database a survival advantage is seen in older dialysis patients accepted for transplantation even after matching for comorbidity. Post-transplant morbidity is mainly attributable to infectious complications and an increased prevalence of malignancy. There is insufficient data about the most optimal immunosuppression regime and further research is required in this direction. The evidence currently supports the use of kidneys from older donors because of a relative lack of cadaveric organs from younger donors although a worse patient and graft outcome is recognized in the long term. Insufficient evidence exists to support a firm conclusion regarding age matching or targeting of older organs to special groups.

Age Factors↗
PubMed1997

Inverse correlation between IgG-antihinge region and antierythrocyte autoantibody in chronic benign and malignant cold agglutination.

Previous reports provided evidence of an immunosuppressive role of natural anti-F(ab')2 antibodies. If suppressive anti-F(ab')2 antibodies also regulated the autoantibody production in cold agglutination, one would expect high titers of anti-F(ab')2 to be associated with low titers of cold agglutinins. Indeed, our previous studies revealed an inverse correlation between IgG-anti-F(ab')2 and cold agglutinins. Many previous experiments focused on anti-F(ab')2 of an antiidiotypic nature. Recent epitope mapping showed that anti-F(ab')2 of healthy persons is not an antiidiotype but recognizes a hinge region sequence. We attempted to answer the question whether this IgG-antihinge antibody is responsible for the previously described association between anti-F(ab')2 and cold agglutinins. IgG-antihinge and IgG-anti-F(ab')2 antibody was determined and statistically analyzed in the serum of 334 patients with cold agglutination. Our experiments revealed a strong correlation between the concentrations of antihinge and the previously described anti-F(ab')2 antibody. The anti-F(ab')2 activity was competitively inhibited by a synthetic hinge peptide. Moreover, patients with high antihinge titers had low cold agglutinin titers, and vice versa. A stratification according to cold agglutinin specificity and disease etiology showed that the inverse correlation is present only in anti-I and anti-i patients suffering from monoclonal B-lymphocyte proliferation. In conclusion, our results confirm the correlation previously described for anti-F(ab')2 antibody and antierythrocyte autoantibody and define for the first time an association between an idiotype-independent anti-IgG autoantibody and cold agglutinin.

Adult↗
PubMed1997

HLA class I DNA typing of 215 "HLA-A, -B, -DR zero mismatched" kidney transplants.

DNA typing for HLA class II improves the typing quality and this was shown previously to be relevant for kidney graft survival. In this project we addressed the question whether molecular typing for HLA class I also increases the efficacy of HLA matching in kidney transplantation. 215 HLA-A,-B,-DR zero-mismatched donor/recipient pairs as defined by serological typing were selected. Retrospective HLA-A and HLA-B typing was performed both by the PCR-SSP and the PCR-SSOP method. DNA typing for HLA-A revealed discrepant results to serology in 5.7% of the donors and 2.8% of the recipients. HLA-B typing discrepancies were found in 6.6% of the donors and 5.6% of the recipients. 10.4% of the donors and 6.5% of the recipients showed either an HLA-A or an HLA-B discrepancy Nearly one-third of the HLA-A discrepancies affected A19 splits. The most common reason for HLA-A discrepancies was the erroneous assignment of serological blanks, whereas HLA-B errors were caused mainly by the assignment of incorrect specificities. DNA typing allowed the definition of HLA-A and -B split specificities in all 118 "splitable" cases for which only broad specificities were reported based on serological typing. A total of 183 DNA class I compatible transplants had a 15% higher one-year graft survival rate than 32 transplants for which DNA typing revealed a class I incompatibility

DNA Probes, HLA↗
PubMed1997

Comparison of typing results by serology and polymerase chain reaction with sequence-specific primers for HLA-Cw in 650 individuals.

HLA-Cw typing by standard serological techniques is associated with a high frequency of blanks, and reliable typing reagents for several of the Cw specificities are scarce. We evaluated the PCR-SSP technique for Cw typing in 370 kidney transplant patients and 280 healthy blood donors. Serological typing of all individuals was performed in our laboratory from 1995 to 1997 using commercially available tissue-typing trays. Comparison between serological and PCR-SSP typing revealed a discrepancy rate of 33.6% (n= 94) in blood donors and 32.4%) (n=120) in kidney recipients. Incorrect antigen assignments occurred only rarely (3.6% of the blood donors and 3.2% of the kidney recipients). The vast majority of discrepancies were due to antigens that were not detected serologically. In 26 individuals no Cw antigen was detected by serological typing, whereas PCR-SSP showed 1 allele in 13 and 2 alleles in the other 13 cases. Another 269 individuals were typed serologically with one blank (presumably homozygous). Of these, only 108 were confirmed to be homozygous, whereas an additional Cw allele was found in the remaining 161 cases using the SSP technique. Most of the "missed" specificities (86.5%) were those for which serological reagents were not available (HLA-Cw*12-*17). The most commonly "missed" specificity was HLA-Cw*1203, which occurred in 13.9% of the healthy blood donors. These results indicate that serological HLA-Cw typing is insufficient for examining the clinical importance of HLA-Cw matching in transplantation. Future studies based on molecular typing should allow the proper investigation of HLA-Cw matching in kidney and bone marrow transplantation.

Alleles↗
PubMed1997

Angiotensin-converting enzyme genotype and renal allograft survival.

Increased activity of the renin-angiotensin system has been implicated in decreased, long-term survival of renal allografts. Recent studies suggest that a deletion variant of the angiotensin-converting enzyme, associated with increased humoral and tissue activity of this enzyme, is a risk factor for the development of diabetic nephropathy and the progression of IgA nephropathy. To determine whether the deletion variant of the angiotensin-converting enzyme gene influences the long-term outcome in renal transplant recipients, the relationship between donor and recipient angiotensin-converting enzyme genotype and clinical outcome were examined over a follow-up period up to 30 mo in a cohort of 269 Caucasian patients undergoing kidney transplantation between 1988 and 1993. In a subsequent case control study, the frequencies of the angiotensin-converting enzyme genotype were compared in a group of Caucasian patients with a graft survival of less than 3 yr (mean survival, 11 mo; n = 328) with the frequencies in patients with a graft survival of at least 3 yr (mean survival, 65 mo, n = 461). Neither in the cohort nor in the case control study was there a significant effect of recipient or donor angiotensin-converting enzyme genotype on transplant survival. Furthermore, the frequency of the angiotensin-converting enzyme deletion allele both in recipients and donors was similar to that reported in Caucasian controls. This study, therefore, does not support the hypothesis that the recipient or donor angiotensin-converting enzyme insertion/deletion polymorphism is an important determinant of transplant survival in Caucasian patients undergoing renal transplantation.

Adult↗
PubMed1997

Highly successful long-term outcome of kidney transplantation in Chinese recipients: an enhancing race effect?

We report on 352 cadaveric kidney transplants and 294 living related transplants performed over a 25-yr period among the Chinese population of Hong Kong. There is a marked preference for transplanting male patients, especially from living donors, and we argue that this represents a cultural phenomenon within the Chinese population. The 10-yr graft survivals for related and cadaveric transplants are 86.2% and 67.4%, respectively. These figures are appreciably higher than corresponding figures in Caucasian populations. We show beneficial effects of using cyclosporin A, minimizing the cold ischemia time and avoiding very young and very old donors. There is a clear benefit of transplanting kidneys with zero or one mismatched HLA antigen against the recipient but no stepwise decrease in outcome as the number of mismatched antigens increases. There is close concordance between the outcome of living related grafts with zero, one, and two mismatched haplotypes against the recipient and no observable benefit of haplotype matching. We show that Chinese renal transplant recipients in other centers also have better long-term graft outcome than Caucasians, both for cadaveric and living related transplants. We draw attention to the existence of a detrimental "race effect" in other studies when Black recipients are compared with Caucasians and consider whether an enhancing race effect exists for Chinese or whether the better outcome reflects different underlying diseases in Chinese.

Actuarial Analysis↗
PubMed1997

Reduced incidence of rectal cancer, compared to gastric and colonic cancer, in a population of 73,076 men and women chronically immunosuppressed.

The incidence of gastric, colonic, and rectal cancers was determined in a cohort of 73,076 men and women chronically immunosuppressed after heart or renal transplantation, to test the hypothesis that there would be a reduced incidence of gastric cancer by dampening chronic gastritis secondary to infection caused by Helicobacter pylori. Follow-up was from 1-13 years. No change in the incidence of gastric cancer was found (32 cases observed, 32.86 expected). An increase in colon cancer was found (75 cases observed, 62.27 expected). A significant reduction in the incidence of rectal cancer was found (15 cases observed, 41.5 expected). This led to a chi2 of 16.92 with 1 degree of freedom, significant at the 0.1% level. The effect was greater in men than women and more marked in heart recipients than in those receiving renal transplants. This unexpected finding led to a review of experiments in mice and rats that present evidence for immune promotion of large-bowel cancers induced by carcinogens by gut-associated lymphoid tissue. We conclude that an analysis of immune function in gut-associated lymphoid tissue in the stomach, colon, and rectum in healthy and immunosuppressed patients may lead to a better understanding of immunosurveillance in the colon and immune promotion of rectal cancers.

Animals↗
PubMed1996

Pretransplant CD4 helper function and interleukin 10 response predict risk of acute kidney graft rejection.

In a prospective study of 80 patients, we investigated the association of acute kidney graft rejection with pretransplant T helper/suppressor activity, B-cell responses, and in vitro cytokine secretion. Patients' CD4+ or CD8+ T cells were cocultured with control B cells and pokeweed mitogen for 6 days. SAC I was used for T cell- and monocyte-independent B-cell stimulation and pokeweed mitogen was used for T cell-dependent B-cell stimulation. B-cell differentiation was assessed in a reverse hemolytic plaque assay. Cytokine responses of T cells (interleukin [IL]-2, IL-10, gamma-interferon) and B cells/monocytes (IL-6, IL-8, tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor) were determined in culture supernatants using ELISA. Subsets of CD4+ T cells, CD8+ T cells, and B cells were assessed by flow cytometry. None of 12 patients with pretransplant CD4 helper defects (CD4 helper activity < 10%) had acute rejection episodes, in contrast to 32 of 68 (47%) patients with normal pretransplant CD4 helper function (P = 0.001). Patients with pretransplant CD4 helper defects also had better 1-year graft function than patients without CD4 helper defects (serum creatinine 1.2 +/- 0.1 mg/dl and 1.7 +/- 0.1 mg/dl, respectively, P < 0.05). Pretransplant IL-10 responses were significantly associated with the occurrence of acute rejection episodes (P = 0.001) and impaired 1-year graft function (P < 0.001). All 14 patients with low pretransplant IL-10 responses (< 100 pg/ml) had 1-year serum creatinine values of < 1.5 mg/dl. Pretransplant B-cell defects and B cell/monocyte-derived cytokine secretion were not related to the incidence of graft rejection or infectious complications. Pretransplant CD8 suppressor-effector (CD11b+), cell counts were significantly associated with the occurrence of infections (P < 0.05). These results show that pretransplant CD4 helper defects and low IL-10 responses predict a low risk of graft rejection, whereas Th1 (IL-2, gamma-interferon) and B-cell/monocyte responses are not of predictive value.

Acute Disease↗
PubMed1996

A natural IgA-anti-F(ab')2gamma autoantibody occurring in healthy individuals and kidney graft recipients recognizes an IgG1 hinge region epitope.

Natural anti-IgG autoantibodies are found both in healthy individuals and in patients with certain diseases. One group of these Abs recognizes epitopes located in the F(ab')2 region of the IgG molecule. The immunoregulatory role of these Abs in healthy individuals, graft rejection, and disease was previously studied, usually with a focus on the characterization of anti-idiotypic Abs. In the present study, we characterize the epitope recognized by an anti-F(ab')2gamma autoantibody of the IgA isotype, which occurs in the serum of healthy individuals and kidney transplant recipients. The autoantibody described herein reacts strongly with F(ab')2gamma but only poorly with Fab(gamma) fragments, a binding pattern pointing to an epitope located in the hinge region. Using synthetic peptides, we identified a conformational epitope that overlaps the middle and part of the lower hinge region. Structural analyses of peptide constructs showed that a defined conformation of the first three residues of the lower hinge is required for a full expression of the epitope. Binding of IgA to the hinge region of IgG1 covers part of the physiologically active Fc domain, immobilizes the Fab arms, and thereby can be expected to exert immunoregulatory functions.

Amino Acid Sequence↗