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C Süsal

Publications and source records attributed to C Süsal.

60 records · Page 4Linked to original sources

Recognition of defined epitopes by affinity-purified anti-immunoglobulin fab autoantibodies isolated from HIV-infected humans.

Infection of humans with HIV-1 has previously been independently shown to result in the generation of autoantibodies (AAbs) reactive with immunoglobulin Fab fragments (Heidelberg), and with autoantibodies to T-cell receptors (TCRs) (Tucson). Here, we carry out epitope mapping studies of affinity-purified AAbs to Fab fragments prepared from individual HIV-positive patients for their capacity to bind recombinant constructs and peptide-defined epitopes modeling TCR and Ig light chains. Some affinity-purified autoantibodies reacted strongly with TCRs expressed by intact T-cells, and recombinant Valpha/Vbeta constructs as well as with certain synthetic peptide epitopes. The binding reactions of affinity-purified AAbs of individual patients were distinct, and the AAb preparations consisted of populations of polyclonal lgs as reflected in specificity and isotype. AAb pools from individual patients all bound particular regions of TCR and Ig chains defined by comprehensive peptide synthesis including the CDR1 and Fr3 segments of the variable domains and the joining segment/switch peptide. In addition, other reactivities to restricted regions of alpha, beta and lambda light chains were documented. These results substantiate the cross-reactivity of TCR and Ig-Fab determinants, and are consistent with the hypothesis that autoantibodies arising as a consequence of HIV infection can have an immunomodulatory role.

Amino Acid Sequence↗

Sequential occurrence of IgM, IgM/IgG, and gp120-IgM/IgG complement complexes on CD4+ lymphocytes in relation to CD4+ blood lymphocyte depletion in HIV+ hemophilia patients: results of a 10-year study.

The concept of autoimmune mechanisms playing an integral role in the pathogenesis of HIV disease is rapidly gaining ground. In this study, we determined IgM and IgG antibodies, complement fragments and gp120 on the surface of CD4+ lymphocytes using double-fluorescence flow cytometry. Sequential analysis demonstrated an inverse relationship of autoantibodies and CD4+ lymphocyte counts in the peripheral blood. HIV+ patients without autoantibodies (16/104 = 15%) had the highest CD4+ blood cell counts (324 +/- 264/microliters; mean +/- SD). CD4+ counts were successively lower in patients with complement-fixing IgM (243 +/- 240/microliter), complement-fixing IgG and IgM (139 +/- 138/microliter), or gp120-IgM/IgG complement complexes on the surface of CD4+ cells (38 +/- 45/microliter, P = 0.03). Individual patient profiles show that IgM autoantibodies typically are formed early after HIV infection and appear to deplete CD4+ lymphocytes very slowly, whereas complement-fixing IgG autoantibodies are generated at a later stage and deplete CD4+ lymphocytes more efficiently. The presence of both soluble gp120 and complement-fixing autoantibodies on CD4+ lymphocytes is associated with very low CD4+ cell counts and coincides with progression to terminal disease. Early during HIV infection autoantibody production is rather unstable, but it becomes more stable with disease progression and persists in advanced stages of the disease. These data suggest that autoantibody formation against CD4+ lymphocytes is a pathogenic mechanism for CD4+ cell depletion.

Antigen-Antibody Complex↗

Advances in pre- and posttransplant immunologic testing in kidney transplantation.

Pre- and posttransplant risk estimation in kidney transplantation is important for the selection of appropriate treatment strategies. Recently, using new immunologic tests, we made observations within the framework of the Collaborative Transplant Study that may influence clinical practice. Complement-dependent lymphocytotoxic panel reactivity as a measure of anti-HLA sensitization, although criticized for its low sensitivity, is a useful indicator of an increased risk of rejection. Using the more sensitive complement-independent ELISA methodology, which utilizes solubilized HLA molecules instead of lymphocytes, we found that recipients with preformed complement-dependent anti-HLA antibodies showed a decreased graft survival only if their antibodies were directed against both HLA class I and class II, whereas isolated reactivity only against HLA class I or class II was of no clinical consequence. Pretransplant serum-soluble CD30 (sCD30) was found to be an independent and highly predictive factor of immunologic risk. The effects of sCD30 and anti-HLA antibodies were additive. Importantly, even patients without anti-HLA antibodies showed a strong HLA matching effect if their pretransplant serum contained high levels of sCD30. Although the role of anti-HLA antibody formation after transplantation remains uncertain, ELISA-detected sCD30 was shown to indicate impending graft rejection as early as on posttransplant days 3 to 5. Another very sensitive indicator of impending rejection is provided by posttransplant monitoring of the cytotoxic T-lymphocyte effector genes, perforin and granzyme B, in peripheral blood using real-time PCR.

Antigens, CD↗

Toxic effects of the herbicide 2,4-dichlorophenoxyacetic acid on lymphoid organs of the rat.

We investigated the toxicity of the widely used herbicide dimethylammonium salt of 2,4-dichlorophenoxyacetic acid (DMA-2,4-D) on the lymphoid system of rats after a single dose oral administration using histological, cytochemical and molecular methods. DMA-2,4-D destroyed in a dose- and time-dependent manner the vascular integrity of the thymus and caused cell depletion in the white pulp of the spleen and in the cortex of the thymus, which was at least partly due to programmed cell death. DMA-2,4-D appeared to have hemolytic activity and caused intravascular hemolysis of erythrocytes. An increased hemosiderin content in macrophages of the spleen indicated phagocytosis of lysed erythrocytes. We conclude that acute DMA-2,4-D herbicide poisoning results in severe damage of the lymphatic organs thymus and spleen.

2,4-Dichlorophenoxyacetic Acid↗