Functional characterization of HP12: a novel immunosuppressant purified from Helleborus species.
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Antigens, CD↗
Biomedical subjects
G Opelz
Publications and source records attributed to G Opelz.
Association of viral load in plasma samples of HIV-infected hemophilia patients with autoantibodies and gp120-containing immune complexes on CD4+ lymphocytes.
OBJECTIVE: We investigated whether the induction of antilymphocyte autoantibodies and immune complexes is associated with the activity of HIV replication. METHODS: Viral HIV-1 RNA was measured in the plasma samples of 84 HIV+ hemophilia patients and correlated with the IgM, IgG, IgM/IgG and IgM/IgG/gp120 load of circulating CD4+ lymphocytes, CD4+ and CD8+ cell counts, plasma neopterin levels and in vitro T-cell responses to mitogens and pooled allogeneic stimulator cells. RESULTS: Compared to patients with no immune complexes, on circulating CD4+ lymphocytes, viral load was increased in patients with IgM, IgM/IgG or IgM/IgG/gp120 complexes. Sequential analysis of HIV+ patients showed that peaks of retroviral activity were associated with the subsequent formation of CD4+ lymphocyte-reactive IgM and IgG autoantibodies and gp120-containing immune complexes. CONCLUSION: The induction of autoantibodies and immune complexes attached to CD4+ lymphocytes is associated with periods of increased viral activity in HIV-infected patients.
Antigen-Antibody Complex↗
Inhibition of HIV-1 rgp120 binding to CD4+ T cells by monoclonal antibodies directed against the gp120 C1 or C4 region.
Reagents which block the interaction of HIV-1 gp120 with CD4+ T cell are of therapeutic interest. We assessed the ability of the murine monoclonal antibody (mAb) 87-135/9 to bind to the rgp120 C1 region and to block the CD4 interaction, and compared this with the reactivity of the rat mAb 388/389 or the human mAbs F105 and b12, which are known to bind within or near the gp120 C4 region. ELISA and surface plasmon resonance measurements showed that mAb 87-135/9 recognized specifically the gp120 C1 peptide HEDIISLWDQSLK (residues 105-117). All four mAbs bound to rgp120 and blocked its interaction with CD4+ T cells. When mAb 87-135/9 was used in combination with one of the other antibodies, its inhibitory effect was additive. A therapeutic approach could be to use a human anti-gp120/CD4bs conformational mAb in combination with a humanized Ab directed against the conserved, linear gp120 C1 epitope and/or an anti-viral drug to hinder the HIV-1 virus and shedded envelope protein to bind to CD4+ T cells.
Amino Acid Sequence↗
Cellular immune defect caused by postsurgical radiation therapy in patients with head and neck cancer.
The effects of locoregional postoperative radiation therapy (60 Gy on average) on cellular immunity were investigated in 11 patients with squamocellular carcinomas of the oral cavity, pharynx, or larynx. During radiation treatment, the total lymphocyte counts, CD8+ T-lymphocyte count, and especially CD4+ T-lymphocyte count decreased significantly. The mean CD4+ T-lymphocyte counts dropped from an average of 739/microl to 183/microl (p <0.001), and the CD4+/CD8+ quotient also decreased significantly. Not only the lymphocyte counts but also the in vitro lymphocyte stimulation responses to several mitogens decreased, with reductions averaging 10% to 50% of normal responses by the end of radiation therapy. Within 3 to 4 weeks after radiation therapy, the CD4+ T-lymphocyte counts and the in vitro lymphocyte stimulation responses showed a tendency toward normalization. This study shows that postoperative locoregional radiation therapy in patients with head and neck cancer induces a severe generalized impairment of cellular immunity.
CD4 Lymphocyte Count↗
Relationship between progression of disease and immunoglobulin A-anti-Fab-/F(ab')2 autoantibodies in patients with head and neck cancer.
Patients with malignant tumors of the head and neck often have immune defects. Higher serum immunoglobulin (Ig)A levels were reported in this group of patients. We investigated whether IgA-anti-Fab- or IgA-anti-F(ab')2 autoantibodies, which have been shown to correlate with severe dysfunction of the immune system, also appear in patients with head and neck cancer. Sera of 110 patients with squamous cell carcinoma (SCCHN), eight patients with adenoid cystic carcinoma, and 57 healthy control subjects were tested by enzyme-linked immunosorbent assay for IgA-anti-Fab autoantibody activity. Patients with head and neck cancer showed a higher IgA-anti-Fab activity (optical density (OD) = 399; n = 118) than did healthy control subjects (OD = 84; n = 57; p < 0.0001). An association between stage of disease and IgA-anti-Fab activity could be established in patients with SCCHN. Patients with stage IV disease had a significantly higher IgA-anti-Fab activity (OD = 538; n = 51) than had patients with stage I disease (OD = 283; n = 18; p < 0.05). Patients with stage II (OD = 293; n = 13) or stage III (OD = 379; n = 28) disease had intermediate activity. Also a higher IgA-anti-Fab activity than in healthy control subjects could be shown in the eight patients with adenoid cystic carcinoma (OD = 314; n = 8; p < 0.01). The highest IgA-anti-Fab activity was observed in eight patients with SCCHN who died within 6 months after testing (OD = 1004; n = 8), suggesting an association between autoimmunity and final desintegration of physiologic body functions. The occurrence of IgA-anti-Fab/IgA-anti-F(ab')2 autoantibodies might be interpreted as an aspect of immune deficiency in patients with malignant tumors of the head and neck.
Antibodies, Anti-Idiotypic↗
Comparison of serological and DNA PCR-SSP typing results for HLA-A and HLA-B in 421 Black individuals: a Collaborative Transplant Study report.
In a recent study, we observed a discrepancy rate of 8.5% between the results of molecular and serological HLA class I typing in Caucasian kidney donors and recipients. In the present study we addressed the question how often black individuals are mistyped using the serological technique. 421 Blacks whose HLA typing results were reported to the Collaborative Transplant Study (CTS) were typed retrospectively for HLA-A and -B using a PCR-SSP method. 78 of the 421 individuals (18.5%) showed a discrepancy for HLA-A and 107 individuals (25.4%) for HLA-B. 36.3% of all individuals tested showed either an HLA-A or an HLA-B discrepancy. 13.1% of the discrepancies at the HLA-A locus were due to antigen misassignments and 4.8% were due to missed antigens. HLA-B discrepancies were caused in 15.7% by antigen misassignments and in 10.5% by missed antigens. These results demonstrate an impressive advantage of the PCR-SSP method for HLA-A and HLA-B locus typing over serological typing in black individuals. The high typing discrepancy rate observed in Blacks provides a strong argument for replacing serological typing by the DNA method. It is likely that this will improve the HLA matching correlation in clinical transplantation in Blacks.
Black People↗
HIV-induced IL-6/IL-10 dysregulation of CD4 cells is associated with defective B cell help and autoantibody formation against CD4 cells.
To analyse CD4 cell cytokine secretion and helper/suppressor function at a clonal level we established 446 CD4+ T cell clones (TCC) in four healthy controls, three HIV- haemophilia patients, four CDC II,III and four CDC IV patients. Spontaneous TCC secretion of Th1 cytokines (IL-2, interferon-gamma (IFN-gamma)) and Th2 cytokines (IL-4, IL-6, IL-10) was determined by ELISA. TCC helper and suppressor functions were tested in a pokeweed mitogen (PWM)-stimulated allogeneic co-culture system using a reverse haemolytic plaque assay for assessment of B cell responses. There was a significant association of TCC surface marker expression (Leu-8, CD45RA) with TCC IL-6 secretion in healthy controls (P < 0.01), HIV- patients (P < or = 0.001) and CDC II,III patients (P < or = 0.01) but not in CDC IV patients. Likewise, TCC expression of Leu-8 and CD45RA was significantly associated with TCC suppressor function in healthy controls (P < or = 0.0005) but not in HIV-infected patients. A reduced TCC helper frequency (< or = 10% of TCC) and an enhanced TCC suppressor frequency (> 80% of TCC) were detected only in those HIV-infected patients who showed an excessively increased TCC IL-6 secretion (> 70% of TCC) together with a significantly diminished TCC IL-10 secretion (< or = 10% of TCC). CD4 cell autoantibodies also were found only in patients with this type of cytokine dysregulation. These data indicate that CD4 cell surface markers lose their functional relevance in HIV-infected patients. HIV-induced IL-6/IL-10 dysregulation of CD4+ T cells, i.e. the up-regulation of spontaneous IL-6 and down-regulation of spontaneous IL-10 secretion, appears to be involved in inducing CD4 helper defects and may promote autoantibody formation against CD4 cells.
Autoantibodies↗
HLA class II (DRB1, DQA1 and DQB1) associated genetic susceptibility in Iranian multiple sclerosis (MS) patients.
The association of HLA class II alleles with multiple sclerosis (MS) has been amply documented. In the present study, the role of HLA class II (DRB1, DQA1 and DQB1) alleles and haplotypes was investigated in 43 unrelated Iranian chronic progressive multiple sclerosis (CP-MS) patients compared with 100 healthy individuals. HLA typing for DRB1, DQA1 and DQB1 was performed by restriction fragment length polymorphism (RFLP). Subtypes of DR4, DR15 and DR16 were defined using polymerase chain reaction (PCR) amplification with sequence-specific primers (PCR-SSP). The results show that, among DR2-positive MS patients and the control group, a positive association with the DRB1*1503, DQA1*0102, DQB1*0602 haplotype (21% vs. 2.7%, P = 0.057, RR = 9.8) and a negative association with the most frequent DR15 haplotype in the control group, DRB1*15021, DQA1*0103, DQB1*0601 (7% vs. 24.3%, P = 0.001), were observed. No significant association was found with the analysed HLA-DRB1, DQA1 and DQB1 alleles.
Alleles↗
Association of chronic kidney graft failure with recipient blood pressure. Collaborative Transplant Study.
Immunological rejection is the most important cause of kidney transplant failure. Recently, nonimmunological causes of long-term allograft failure have become more widely appreciated. In primary chronic renal disease, blood pressure is of overriding importance for long-term renal function. The role of blood pressure in determining long-term transplant outcome has not yet been established. We studied the influence of blood pressure post-transplantation on long-term kidney graft outcome in 29,751 patients. Outpatient blood pressure measurements were recorded and reported to the Collaborative Transplant Study. Graft and patient survival rates were analyzed over seven years in relation to blood pressure. Increased levels of systolic and diastolic blood pressure post-transplantation were associated with a graded increase of subsequent graft failure (P < 0.0001). Chronic graft failure was significantly associated with blood pressure even when patient death was censored (P < 0.0001). Cox regression analysis established increased blood pressure as an independent risk factor for graft failure. We conclude that post-transplant blood pressure is a highly significant predictor of long-term kidney graft outcome. Whether aggressive lowering of blood pressure improves long-term transplant outcome will have to be studied prospectively.
Blood Pressure↗
Distribution of human platelet antigens in a Chinese population.
We report the distribution of the human platelet antigens HPA-1, -2, -3, -4 and -5 as determined using the polymerase chain reaction with sequence-specific primers in 100 random, healthy Chinese in Hong Kong. The HPA-1a, -2a, -4a and -5a genes were present in every sample tested, HPA-1b, -2b and -5b were rare, and the sample was monomorphic for HPA-4a. HPA-3a and -3b genes showed frequencies of 0.525 and 0.475 respectively. There was no departure from Hardy-Weinberg equilibrium in any of the five HPA systems studied.
Antigens, Human Platelet↗
Natural anti-immunoglobulin autoantibodies: irrelevant by-products or immunoregulatory molecules?
Anti-immunoglobulin autoantibodies (anti-Ig auto-Abs), particularly IgM-anti-IgG (classical rheumatoid factor), have been studied mainly in the context of rheumatoid arthritis. In this article we focus on other members of the anti-Ig family, including the natural IgG-anti-F(ab')2 auto-Ab, and look for clinical and experimental findings supporting a role of these antibodies in the regulation of the immune response. We discuss the evidence for suppression of auto- and alloreactive B cells by IgG-anti-F(ab')2 auto-Ab and the role of this Ab in the pathogenesis of certain diseases, such as autoimmune hemolytic anemia. The structure of the antibody's antigen-binding site was clarified by isolating the VL and VH gene segments from the cDNA of B cells. Sequence analyses revealed germline gene identity of VL chains and 88% homology with the closest germline gene of VH chains. Finally, we discuss hypothetical models concerning the immunoregulatory role of natural anti-Ig auto-Abs.
Adjuvants, Immunologic↗
Renal transplantation in secondary systemic amyloidosis.
When renal amyloidosis has progressed to end-stage renal failure, most patients are severely affected by systemic amyloidosis and nephropathy. An alternative to chronic dialysis is renal transplantation. We present a patient with amyloid nephropathy who developed recurrent transplant amyloidosis. Renal transplantation was performed in 1985 with a living related donor. In 1990 the patient developed amyloidosis of the graft with membranous nephropathy and tubular acidosis due to hyporeninemic hypoaldosteronism. Secondary amyloidosis has been reported to involve glandular organs inducing hypothyroidism, hypocortisolism and hypoaldosteronism. Cyclosporine has been reported to induce hyporeninemic hypoaldosteronism and tubular acidosis, but not hypocortisolism and hypothyroidism. Progression of the amyloidosis of the graft was confirmed by a renal biopsy in 1993. Data published in the literature indicate that the survival rate of amyloidotic graft recipients is worse than those of non-amyloidotic graft recipients. This was confirmed in an analysis of the current CTS data which showed an impaired survival rate at 5-yr of 66 +/- 4% (+/- SE) for patients with amyloidosis (n = 413) as compared with 86 +/- 1% (p < 0.0001) for patients with glomerulonephritis and 84 +/- 1 (p < 0.01) for patients with polycystic kidney disease. Graft survival after 5 years was 55 +/- 4% in patients with amyloidosis as compared with 63 +/- 1% (p = 0.02) in patients with glomerulonephritis and 68 +/- 1% in patients with polycystic kidney disease. Graft survival was improved in amyloidotic patients treated with cylosporine as compared with patients on steroids and azathioprine (55 +/- 4% vs. 38 +/- 8%, p < 0.05). It is concluded that renal transplantation is the renal replacement therapy of choice for patients with AA-type amyloidosis although the overall patient survival is impaired in comparison with patients with other diseases.
Adult↗
Non-immune mechanisms of progressive graft dysfunction.
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Cardiovascular Diseases↗
Cadaver kidney graft outcome in relation to ischemia time and HLA match. Collaborative Transplant Study.
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Cadaver↗
[Chronic liver immunologic factors in ischemic type biliary lesions (ITBL) --> reduced Th1 and increased Th2 response].
Compared to patients with a stable liver function, we found a decreased Th1 and increased Th2 response in patients presenting with ischemic type biliary lesions following liver transplantation. It remains open to speculation whether these immunological changes were induced by the damage of the bile ducts, occur as an additional damaging factor or are found as an epiphenomenon in patients with liver transplant dysfunction.
Bile Ducts↗
Impact of HLA compatibility on survival of kidney transplants from unrelated live donors.
BACKGROUND: Kidney transplants from unrelated live donors have been reported to perform exceedingly well despite poor HLA compatibility. These results were extrapolated to indicate that HLA matching in cadaver kidney transplantation is superfluous provided the ischemic preservation time is kept very short. METHODS: The influence of HLA matching on the outcome of 2281 transplants from unrelated live donors from 1986 to 1995 was analyzed at 198 transplant centers. RESULTS: The 5-year transplant success rate was significantly associated with the number of HLA-A, -B, and -DR mismatches (P<0.0001). There was a significant impact on graft survival of mismatches at the class I HLA-A, and -B loci (P=0.001) as well as at the class II HLA-DR locus (P=0.005). In transplants from both spouses and nonspouses, cases with no HLA-DR mismatch were found more often than would be expected if transplant donors were selected by chance, which indicates that efforts of prospective HLA matching had been made. CONCLUSIONS: The outcome of kidney transplants from unrelated live donors is strongly influenced by HLA compatibility. Short exposure of donor kidneys to ischemia does not eliminate the influence of HLA matching on graft survival.
Female↗
Clinical relevance of HLA-DPB locus matching for cadaver kidney retransplants: a report of the Collaborative Transplant Study.
BACKGROUND: Matching for the HLA class I loci A and B and for the HLA class II locus DRB is known to influence the survival rate of kidney transplants. It is unknown whether matching for the HLA class II locus DPB also exerts an influence on graft outcome. METHODS: The influence of matching for the HLA-DPB locus was analyzed based on DNA typing results obtained in more than 3600 first and 1300 repeat cadaver kidney transplants. RESULTS: HLA-DPB mismatches had no deleterious influence on the outcome of first cadaver transplants. However, the influence was statistically significant for retransplants. One-year graft survival rates were 83+/-2% with no mismatch (n=345), as compared with 76+/-2% with one mismatch (n=702, P=0.02), and 73+/-3% with two mismatches (n=258, P=0.003). The deleterious influence of HLA-DPB mismatches was particularly strong in retransplant recipients with >50% reactivity of preformed lymphocytotoxic antibodies, for which the 1-year graft survival rate was 70+/-4% with no mismatch, as compared with 69+/-3% with one mismatch (P=0.05) and 61+/-5% with two mismatches (P=0.003). CONCLUSIONS: These results indicate that HLA-DPB is a clinically relevant histocompatibility locus in cadaver kidney retransplantation. It is proposed that prospective typing and matching for HLA-DPB should be implemented for cadaver kidney retransplants.
Cadaver↗
Prospective evaluation of pretransplant blood transfusions in cadaver kidney recipients.
BACKGROUND: A beneficial effect of pretransplant transfusions on graft survival was demonstrated in the early 1970s. In the mid-1980s, however, retrospective studies showed that transfusions had lost their graft-protective effect in the cyclosporine era. During the last 10 years, deliberate transfusion pretreatment of transplant patients has been discontinued. METHODS: Within a collaborative project of 14 transplant centers, prospective recipients of cadaver kidney grafts were randomized to receive either three pretransplant transfusions or transplants without transfusions. RESULTS; The graft survival rate was significantly higher in the 205 transfusion recipients than in the 218 patients who did not receive transfusions (at 1 year: 90+/-2% vs. 82+/-3%, P=0.020; at 5 years: 79+/-3% vs. 70+/-4%, P=0.025). Cox regression analysis showed that this effect was independent of age, gender, underlying disease, prophylaxis with antilymphocyte antibodies, and preformed lymphocytotoxins. CONCLUSIONS; Transfusion pretreatment improves the outcome of cadaver kidney transplants even with the use of modern immunosuppressive regimens.
Blood Transfusion↗