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Biomedical subjects

G Opelz

Publications and source records attributed to G Opelz.

At least 199 records · Page 11Linked to original sources

Anti-IgG autoantibodies in HIV-infected hemophilia patients.

Sera of 76 HIV-negative hemophilia patients, 103 HIV-positive (HIV+) hemophilia patients free of AIDS or AIDS related complex (ARC), and 32 HIV+ hemophilia patients with AIDS/ARC were tested for four different anti-IgG activities. IgG-anti-F(ab')2 gamma, IgM-anti-F(ab')2 gamma, and IgG-anti-Fc gamma serum activities were significantly associated with the clinical stage of HIV infection, whereas IgM-anti-Fc gamma was not. IgG-anti-F(ab')2 gamma activity was found to be caused by cross-reaction of anti-HIV antibody with an epitope within the constant CH1 domain of human IgG. HIV+ hemophilia patients with severe thrombocytopenia (less than 50,000/microliters platelet counts) had significantly higher IgM-anti-IgG activity than patients with greater than 50,000/microliters platelets. Because anti-IgG antibodies possess immunoregulatory properties, our results may serve as a possible explanation for the frequent B cell disorders encountered in HIV-infected patients.

AIDS-Related Complex↗

Survival of DNA HLA-DR typed and matched cadaver kidney transplants. The Collaborative Transplant Study.

The clinical value of serological HLA matching for cadaver kidney transplantation remains uncertain because the success rate for HLA-matched cadaver transplants is lower than that of HLA-matched sibling grafts. Up to 25% of serological HLA-DR typings may be incorrect when compared with a more accurate DNA-RFLP method, and we have now examined whether incorrect HLA-DR typings account for the lower than expected success rates of HLA-matched cadaver transplants. 58 transplant centres took part in this study and DNA was extracted from over 4000 samples of frozen tissue at the study centre. 8 laboratories then completed blind RFLP typing for HLA-DR. Serological typing data were reported by individual transplant laboratories. 29 of 107 transplants (27%) that were reported as HLA A, B, DR compatible and 76 of 273 (28%) transplants that were reported as HLA B, DR compatible according to serological typing were found to be HLA-DR mismatched by DNA typing. The one-year transplant success rate for DNA-matched HLA, A, B, DR grafts was 87% compared with 69% for mismatched grafts (p less than 0.02); the corresponding success rate for DNA-matched HLA B, DR grafts was 85% compared with 72% for mismatched grafts (p less than 0.01). Many transplants that were previously thought to be HLA matched are mismatched, and this finding may account for previously unexplained graft failures.

Cadaver↗

Autoantibodies against CD4 cells are associated with CD4 helper defects in human immunodeficiency virus-infected patients.

To investigate whether autoantibodies against CD4-positive lymphocytes might induce helper dysfunction, autoantibody formation and T-cell function was examined simultaneously in 61 hemophilia patients. Twenty patients were human immunodeficiency virus (HIV)-negative, 26 HIV-positive stage CDC II or III, and 15 were HIV-positive stage CDC IV. T lymphocytes, CD4-positive, or CD8-positive T subsets were cocultured with B lymphocytes and pokeweed mitogen (PWM) for 6 days and Ig-secreting cells were assessed in a reverse hemolytic plaque assay. The presence of IgM, IgG, C3d, or gp120 on the surface of T cells or T subsets was analyzed by flow cytometry. Autoantibodies against CD4-positive T cells were not detected in controls or HIV-negative patients, but were common in HIV-positive patients (20 of 41 patients). In patients with autoantibodies we found an increased incidence of CD4 helper defects (P less than .0001 in CDC II or III patients; P less than .02 in CDC IV patients). 12 of 13 patients with IgM autoantibodies and 4 of 4 with IgG autoantibodies showed CD4 helper defects. Complement fixation had no relevance. Autoantibody formation against CD4 cells was not due to increased in vivo B-cell stimulation (spontaneous plaque formation: 611 +/- 204 PFC/10(6) B cells in autoantibody-negative patients v 650 +/- 202 PFC/10(6) B cells in autoantibody-positive patients; not significant). Thus, our results suggest that autoantibody formation is not caused by a general state of in vivo B-cell activation. Rather, the production of autoantibodies appears to coincide with defects in B-cell proliferation or differentiation, as shown by reduced mitogen-stimulated B-cell responses in CDC II and III patients (P less than .05). Autoantibodies against CD4 cells appear to be involved in the pathogenesis of CD4 helper defects of HIV-infected patients.

Antigens, CD↗

Improving CD4+ lymphocyte counts in HIV-infected hemophilia patients. A favorable prognostic indicator?

CD4+ lymphocyte counts of 91 HIV+ hemophilia patients were monitored for a mean of 4 years (range: 15-69 months). CD4+ lymphocytes decreased in 55 but increased in 36 patients over time. The CD4+ cell increases were persistent in 5 patients, whereas they fluctuated in 31. Of the 36 patients with increasing CD4+ counts 3 developed AIDS and 1 LAS. The other 32 patients were clinically asymptomatic (CDC II), but had immunological abnormalities, such as increased serum neopterin (N = 18) and impaired in vitro T cell responses to pooled allogenic stimulator cells (N = 15) or mitogens (N = 18). In contrast, of the 55 patients whose CD4+ cells decreased, 24 developed AIDS and 5 ARC (P less than 0.0005). Only 2 of these 55 patients had normal mitogen stimulation in vitro and normal serum neopterin levels.

Acquired Immunodeficiency Syndrome↗

[Hepatitis C virus antibodies in patients following blood transfusion and kidney transplantation].

The prevalence of anti-HCV in patients after kidney transplantation was tested by HCV-Antibody-ELISA (Ortho Diagnostics). In addition, reactive samples were tested by HCV-EIA (Abbott Laboratories), neutralization, anti-HBc (Corzyme, Abbott) and by HBs-Ag (Auszyme, Abbott). 27 of 271 patients (10%) were anti-HCV positive. Receiving more than one kidney graft (TPL) or the transfusion of more than four blood units (BU) increases the risk of HCV infection four times (OR: 4.1; p less than 0.01) or 2.5 times (OR: 2.5; p less than 0.05), respectively, compared with one TPL or less than 4 BU. Receiving more than one kidney graft and transfusion of more than four BU raises the risk of HCV infection 6.8 times. 52% of anti-HCV positive patients were anti-HBc positive, 48% were anti-HBc negative as well as HBs-Ag negative.

Blood Transfusion↗

Collaborative Transplant Study Kidney Exchange Trial for highly sensitized recipients.

1. A better than 70% 1-year graft success rate was obtained in highly sensitized recipients of first and second kidney transplants. Recipients of third or fourth transplants had a 25% lower success rate. 2. The results of this trial show a strong influence of HLA matching in highly sensitized recipients. HLA-DR mismatches appear to be most deleterious, followed by HLA-B mismatches. 3. Thirty transplants with 0 mismatches for HLA-B, -DR had an excellent 88% 1-year graft survival rate. 4. The strong effect of HLA matching mandates the national and international exchange of kidneys for highly sensitized recipients.

Follow-Up Studies↗

Human leucocyte antigens in idiopathic nephrotic syndrome in children.

An association of the idiopathic nephrotic syndrome (NS) with certain human leucocyte antigens (HLA) has been reported repeatedly. The aim of this study is to characterize further the clinical and histological features of patients with NS in relation to their HLA phenotypes. HLA antigens were determined in 132 paediatric patients with NS. In 91 steroid-sensitive patients (usually associated with minimal glomerular changes), the antigen frequencies of HLA-DR3, HLA-DR7, and HLA-B8, -DR3 combined were significantly increased compared with controls. The strongest association was observed with the combined occurrence of HLA-B8, -DR3, -DR7 (relative risk 21.5). This association and that with HLA-DR3 alone were strongest in the presence of frequent relapses and steroid dependence compared with children without or with infrequent relapses. The pattern of HLA antigens was similar in the 57 steroid-sensitive patients with biopsy-proven minimal glomerular changes. In 41 children with steroid-resistant NS (usually associated with focal segmental glomerulosclerosis) a similar trend for increased antigen frequencies was found but the data were significant only for the combined occurrence of HLA-B8, -DR3 and -DR7. In all patients combined the frequency of the HLA associations was significantly lower when the age of onset was greater than 8 years compared with that of younger patients. It is concluded that the immunogenetic background of the steroid-sensitive and steroid-resistant NS is different and age-dependent.

Adolescent↗

Role of anti-IgG autoantibodies in kidney transplantation.

To demonstrate whether anti-IgG autoantibodies of different isotypes and specificities play a role in kidney transplantation, pretransplant sera of recipients (a) with well-functioning grafts (n = 40); (b) with reversible rejection episodes that were treated successfully (n = 63); and (c) with irreversible graft rejection (n = 40) were tested for four different anti-IgG autoantibody activities. A protective effect of IgG-anti-F(ab)2 gamma antibodies on graft survival was observed (p less than 0.01). High pretransplant IgG-anti-Fc gamma activity was found to be associated with a low kidney graft survival rate (p less than 0.02). Pretransplant IgM-anti-F(ab)2 gamma and IgM-anti-Fc gamma activities showed no effect on kidney graft outcome.

Antibodies, Anti-Idiotypic↗

Long-lasting kidney graft survival after immunization with antibody-coated blood cells: mediation by immunosuppressive autoantibodies.

Treatment of LEW rats before transplantation with BN blood cells preincubated with LEW-anti-BN serum resulted in prolonged BN kidney graft survival (untreated, 8 +/- 0.4 days; pretreated, 124 +/- 36). The serum of pretreated animals contains a factor which suppresses T cell proliferation against donor antigens. This effect was not mediated by antiidiotypic antibodies because it was reproduced in a donor-unrelated system. The serum and IgG of pretreated animals also suppressed the humoral immune response. As for T cells, the antibody-suppressive effect was not donor-restricted. A broadly reactive anti-immunoglobulin (anti-B cell) autoantibody was found in the IgG fraction of immunized animals. The mediation of immunosuppression by broadly reactive anti-B and T cell autoantibodies induced by the immunization with antibody-coated blood cells is discussed.

Animals↗