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C Süsal

Publications and source records attributed to C Süsal.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Illness stage and IgA-anti-Fab/F(ab')2 autoantibody activity in serum of patients with malignant head-neck tumors].

BACKGROUND: Patients with malignant tumors of the head and neck often show immune defects. Increased serum IgA levels have been reported in these groups 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. PATIENTS: Sera of 110 patients with squamous cell carcinoma, eight patients with adenoid cystic carcinoma, and 57 healthy controls were tested with an ELISA for IgA-anti-Fab autoantibody activity. RESULTS: Patients with head and neck cancer showed a higher IgA-anti-Fab activity (OD:399, n = 118) than healthy controls (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. Stage IV patients had a significantly higher IgA-anti-Fab activity (OD: 538, n = 51) than stage 1 patients (OD: 283, n = 18, p < 0.05). Patients with stage II (OD: 293, n = 13) or stage III (OD: 379, n = 28) showed intermediate activity. Also a higher IgA-anti-Fab activity than in healthy controls was demonstrated in the eight patients with ACCHN (OD: 314, n = 8, p < 0.01). The highest IgA-anti-Fab activity was observed in eight patients with SCCHN who died within six months after testing (OD: 1004, n = 8). Similar results were obtained for IgA-anti-F(ab')2 autoantibodies. Our findings suggest an association between autoimmunity and final desintegration of physiological body functions. CONCLUSIONS: 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.

Adult↗
PubMed1996

CD8+ lymphocyte decrease in HIV disease: association with anti-CD4+ but not with anti-CD8+ lymphocyte autoantibodies.

HIV+ patients form autoantibodies against CD4+ and CD8+ lymphocytes. It was shown that anti-CD4+ lymphocyte autoantibodies are associated with the depletion of CD4+ cells. In the present study we analyzed the relationship of anti-CD4+ and anti-CD8+ autoantibodies with the CD8+ lymphocyte decrease commonly observed during HIV disease. IgM and IgG antibodies as well as complement fragments were determined on the surface of CD4+ and CD8+ lymphocytes using double fluorescence flow cytometry. Anti-CD8+ lymphocyte autoantibodies were found more often in HIV + hemophilia patients (75/105 = 71%) than HIV- hemophilia patients (13/37 = 35%; p < 0.0001), patients with pharyngeal carcinoma (20/44 = 45%; P = 0.002), habitual abortions (3/13 = 23%; p = 0.0009) or healthy individuals (93-223 = 42%; p < 0.0001). Anti-CD8+ antibodies, mostly of the IgM type, occurred significantly more frequently than anti-CD4+ antibodies in healthy controls (p < 0.0001), patients with pharyngeal carcinoma (p = 0.0001), or HIV- patients (p = 0.01). In HIV+ patients, however, anti-CD4+ autoantibodies were found more often than anti-CD8+ antibodies (85 vs 71%; p = 0.02). 70 of 104 (67%) HIV+ patients had autoantibodies on both CD4+ and CD8+ lymphocytes and the IgG/IgM/C3d autoantibody pattern was identical in 31 (44%) of the patients. Interestingly, peripheral blood CD8+ cell counts were significantly associated with anti-CD4+ (p = 0.01) but not with anti-CD8+ lymphocyte autoantibodies. It is hypothesized that the inhibition and depletion of CD4+ cells by anti-CD4+ autoantibodies is associated with a loss of regulatory functions that leads to a depletion of antiviral cytotoxic CD8+ lymphocytes.

Autoantibodies↗
PubMed1995

Interaction of complement and specific antibodies with the external glycoprotein 120 of HIV-1.

Previously we have investigated the interaction of human complement as well as one polyclonal and three human monoclonal antibody preparations with the human immunodeficiency virus type-1 (HIV-1) transmembrane recombinant glycoprotein (rgp41). A strong competition was found between the antibodies and deposited complement proteins for the same binding sites located within the immunodominant region of rgp41. The aim of the present experiments was to see if the same type of antibody-complement-HIV-1 interactions could be observed with the outer envelope glycoprotein (rgp120) of HIV-1. Three different glycosylated rgp120 preparations, as well as a synthetic peptide corresponding to the V3 loop of the MN strain, were adsorbed to enzyme-linked immunosorbent assay (ELISA) plates and incubated with mixtures of anti-rgp120 antibodies and normal human serum (NHS) as a complement source. Fixed complement proteins and antibodies were detected with specific, peroxidase-labelled antibodies against different complement proteins (C1q, C4b, C3b) and the gamma-chain of antibodies. In the absence of anti-rgp120, high amounts of C3 were deposited to each rgp120 preparation tested (including the V3 peptide) but significant differences in the amounts of bound C1q and C4b were observed. Using sera deficient in different complement proteins, we found that both the classical and the alternative pathways contributed to the C3 binding to rgp120. Addition of specific antibodies did not increase complement activation by rgp120 and only in the case of a monoclonal antibody to the V3-loop could we see complement-dependent inhibition of antibody binding.

Antibodies, Monoclonal↗
PubMed1994

Complement activation by recombinant HIV-1 glycoprotein gp120.

The mechanism of CD4+ cell depletion in HIV-infected patients is poorly understood. In this study we investigated whether rgp120 can activate the complement system in the absence of anti-gp120 Abs. We found that the complement proteins C4, C3d, C5b-9, and properdin bind to rgp 120-coated CD4+ T cells of healthy individuals when incubated in autologous serum. Activation of the complement system occurred primarily via the classical pathway and was abolished in sera deficient in C1q and C4 as well as in the presence of EDTA. No cell lysis was observed in a lymphocytotoxicity assay using human serum, possibly because of homologous restriction of complement lysis. In contrast, addition of rabbit sera induced lysis of the rgp 120-precoated cells. Cell lysis by rabbit serum was found to be because of naturally occurring IgM anti-gp 120 Abs. The rgp 120, which was immobilized on the surface of microtiter plates activated complement in the absence of lymphocytes. Complement activation by cell-bound HIV-1 envelope glycoprotein gp120 with subsequent opsonization may be relevant for the elimination of noninfected CD4+ T cells in HIV-infected patients.

Amino Acid Sequence↗
PubMed1994

Association of IgA-anti-Fab autoantibodies with disease stage in head-and-neck cancer.

Patients with head-and-neck cancer commonly have immune defects. It was reported that these patients have raised serum IgA levels. We investigated whether IgA-anti-Fab autoantibodies, which occur in association with immune dysfunction, are present in patients with head-and-neck cancer. Sera of 101 patients with squamous-cell carcinoma (SCCHN) and 8 patients with adenoid cystic carcinoma (ACCHN) of the head and neck were tested in ELISA for IgA-anti-Fab autoantibody activity. IgA-anti-Fab serum activity was significantly higher in both SCCHN and ACCHN patients than in healthy controls. In patients with SCCHN, an association between disease stage and IgA-anti-Fab activity was established. Stage-IV patients had significantly higher IgA-anti-Fab than stage-I patients or healthy controls. Stage-II and stage-III patients had intermediate levels. Extremely high IgA-anti-Fab activity was observed in 7 patients who died within 6 months following testing, suggesting a relationship of autoimmunity with terminal disintegration of physiological body functions. IgA-anti-Fab autoantibodies may explain the occurrence of immune defects in patients with head-and-neck cancer.

Adult↗
PubMed1994

Comparative study of antibodies that are associated with disease progression in HIV disease.

Two types of antibodies which previously were found to be inversely associated with CD4+ cell counts and which may contribute to the progression of HIV disease were measured in parallel in 55 serum samples of 7 longitudinally tested HIV-infected patients (4 homosexual men, 3 haemophilic men) and in 15 serum samples from 15 patients with advanced AIDS. HIV-infection enhancing antibodies were determined in the presence of near-physiologic human complement concentration using a complement receptor type 2 (CR2) carrying HIV-target cell line. IgG and IgA class autoantibodies directed against human IgG-Fab fragments were measured in specific ELISA assays. In agreement with our previous studies obtained in HIV-seropositive haemophilic patients, significant negative correlations were found between CD4+ cell counts and IgG anti-Fab and IgA anti-Fab antibodies (Spearman correlation coefficient r = -0.587, P < 0.0001; and r = -0.269, P = 0.024, respectively). A significant positive correlation was observed between complement-dependent enhancing antibodies and IgA anti-Fab antibodies (r = 0.408, P = 0.003), whereas the correlation with IgG anti-Fab antibodies was only weak (r = 0.288, P = 0.034). Serum samples with high titres of complement-dependent enhancing antibodies had almost 3 times higher IgA anti-Fab autoantibody activity than sera with low titres (P = 0.0038). Our findings indicate that the two disease markers in HIV disease, enhancing antibodies and autoantibodies directed against the Fab moiety of IgG, are not identical. However, anti-Fab antibodies may contribute to complement-dependent HIV infection enhancement.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Isotypes and IgG subclasses of anti-Fab antibodies in human immunodeficiency virus-infected hemophilia patients.

We reported recently that anti-Fab autoantibodies of the IgG isotype are associated with the decrease of helper/inducer (CD4+) lymphocytes in human immunodeficiency virus-infected (HIV+) hemophilia patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). In the present study we investigated the subclass distribution of IgG-anti-Fab autoantibodies, and whether anti-Fab antibodies of the IgA and IgM isotypes also are associated with the development of AIDS. Sera of HIV+ patients with AIDS had significantly higher IgA-anti-Fab activity than HIV+ patients with ARC (p < 0.02), HIV+ patients without AIDS/ARC (p < 0.0001), HIV-negative (HIV-) patients (p < 0.001), or healthy controls (p < 0.0001). An inverse association was found between IgA-anti-Fab activity and CD4+ cell counts (r = -0.396, p < 10(-6)). In contrast, no association of CD4+ cell counts was observed with IgM-anti-Fab. However, IgM-anti-Fab was significantly increased in patients with thrombocytopenia. We found a significant association between IgA-anti-Fab activity and serum neopterin concentrations (r = 0.310, p < 10(-5)). IgG-anti-Fab activity was detected mainly in the IgG3 fraction, although in HIV+ patients with AIDS/ARC various IgG subclasses were present. Affinity-purified anti-Fab antibodies isolated from sera of AIDS patients bound to rgp120-preincubated CD4+ cells of a healthy individual, supporting our hypothesis that anti-Fab antibodies and free circulating gp120 molecules are involved in the elimination of uninfected CD4+ cells. Removal of anti-Fab autoantibodies from the circulation by immune adsorbance might be a useful approach in the treatment of AIDS.

AIDS-Related Complex↗
PubMed1994

Pretransplant serum IgA concentration and IgA-anti-Fab autoantibody activity as prognostic indicators of kidney graft survival.

IgA concentration and IgA-anti-Fab autoantibody activity were tested in pretransplant sera of 308 kidney graft recipients. Recipients with a serum IgA concentration of 2 g/l or greater had a 1-year graft survival rate of 83%, compared with a 68% rate in recipients with serum IgA of less than 2 g/l (P < 0.005). Serum IgA concentration and IgA-anti-Fab autoantibody activity were significantly associated (r = 0.38, P < 0.0001). Recipients with a high pretransplant IgA-anti-Fab activity had a significantly better graft survival rate (81%) than patients with low pretransplant IgA-anti-Fab (67%, P < 0.025). When IgA-anti-Fab and serum IgA were considered together, 137 recipients with high IgA-anti-Fab and high serum IgA had a 86% 1-year graft survival rate, which was significantly better than the 63% survival rate in patients with low IgA-anti-Fab and low serum IgA (P < 0.0005). The pretransplant serum IgA level and IgA-anti-Fab autoantibody activity were excellent predictors of kidney graft outcome.

Autoantibodies↗
PubMed1993

Complementarities and network interactions in AIDS.

The contribution of autoimmune phenomena to the development of AIDS is not fully understood. In this paper we provide new evidence that idiotypic network interactions are operative in the development of AIDS. We furthermore present a model that involves two groups of antibodies and other molecules that are related to each other by a network of specific complementarities. We define Group I molecules to include antibodies and other molecules that have direct or indirect similarities with class I MHC molecules, and Group II substances that have similarities with class II MHC. We observe an inverse relationship between Group I antibodies (including anti-Fab) and Group II antibodies (including anti-anti-gp120, anti-anti-CD8 and anti-rCD4). The potential roles of members of these two groups in AIDS pathogenesis and/or protection are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1993

IgA-anti-Fab autoantibodies and disease progression in AIDS.

There is increasing evidence that autoimmune phenomena contribute to the pathogenesis of the acquired immunodeficiency syndrome (AIDS). We investigated the relationship between IgA autoantibodies directed against the Fab part of the IgG molecule and disease progression in 87 HIV-infected hemophilia patients. AIDS patients demonstrated a significantly higher serum IgA-anti-Fab activity than HIV-positive (HIV+) patients with AIDS-related complex (ARC) (P < 0.02), HIV+ patients without AIDS/ARC (P < 0.0001), HIV negative (HIV-) patients (P = 0.0001), or healthy controls (P < 0.0001). Moreover, an inverse association was observed between serum IgA-anti-Fab activity and CD4+ cell counts (r = -0.396, P < 10(-6)). This close association was confirmed in longitudinal studies of symptomatic patients. IgA-anti-Fab antibodies are suggested to play an important role in the immunopathogenesis of AIDS, and their determination may be helpful in the monitoring of HIV-infected patients.

AIDS-Related Complex↗
PubMed1993

Association of T cell and macrophage dysfunction with surface gp 120-immunoglobulin-complement complexes in HIV-infected patients.

The mechanism of CD4+ cell depletion and functional T helper cell inhibition in HIV-infected individuals is poorly understood. The present study demonstrates that immune complex-covered CD4+ cells are associated with T cell inhibition and macrophage stimulation. We studied 30 patients with ARC/AIDS and 35 asymptomatic HIV+ haemophilia patients. Overall, 20 +/- 3% of peripheral CD4+ lymphocytes were covered with gp120 (range 0-94%). gp120+ cells also exhibited surface-bound IgG (P = 0.0001), IgM (P = 0.0001), and complement (P = 0.0001). Decreased in vitro lymphocyte proliferation was associated with the immune complex load of CD4+ cells. The higher the percentage of CD4+ gp 120+ cells in the blood, the lower the T cell response in vitro (P = 0.001). Moreover, an association was found between immune complex-positive cells and plasma neopterin (P = 0.01). Patients with increased plasma neopterin levels had decreased in vitro responses to pokeweed mitogen (PWM) (P = 0.006), phytohaemagglutinin (PHA) (P = 0.004), concanavalin A (Con A) (P = 0.09), and anti-CD3 MoAb (P = 0.03), and decreased CD4+ cell counts in the blood (P = 0.006). Since maximally 1% of CD4+ lymphocytes are infected with HIV, T cell dysfunction and T cell depletion in HIV-infected patients may also be caused by the release of free gp120 that binds to uninfected CD4+ cells. Our data suggest that the functional inhibition and subsequent elimination of uninfected CD4+ lymphocytes with surface gp120-immunoglobulin-complement complexes may be a pathomechanism in the manifestation of AIDS.

Antigen-Antibody Complex↗
PubMed1993

CD4+ lymphocyte depletion in HIV-infected patients is associated with gp120-immunoglobulin-complement attachment to CD4+ cells.

The mechanism of CD4+ lymphocyte depletion, which is the main immunological feature in HIV-infected patients, is unclear. We investigated whether gp120-immunoglobulin-complement complexes on the surface of CD4+ cells might be involved in the elimination of CD4+ lymphocytes. The results obtained in 63 HIV-infected patients show that gp120 is attached to a variable degree to CD4+ cells. Importantly, the percentage of CD4+gp120+ lymphocytes is inversely associated with CD4+ lymphocyte counts in the peripheral blood (p = 0.0004). CD4+gp120+ blood lymphocytes bind IgM (p = 0.0027) and IgG antibodies (p = 0.0001) and complement (p = 0.0005). These results suggest that immune complex-mediated cell elimination is an important mechanism of CD4+ cell depletion in patients with AIDS.

Antigen-Antibody Complex↗
PubMed1993

Molecular mimicry between HIV-1 and antigen receptor molecules: a clue to the pathogenesis of AIDS.

There is increasing evidence that autoimmune phenomena play an important role in the immunopathogenesis of AIDS. We found a high degree of sequence homology between HIV-1 and antigen receptor molecules, immunoglobulins and T cell receptors. Based on recent findings that the appearance of anti-Fab autoantibodies and attachment of gp120/immunoglobulin/complement complexes on CD4+ T cells are associated with the decrease of CD4+ T cells in HIV-infected patients, we hypothesize herein that cross-reactive anti-F (ab')2 autoantibodies and circulating gp120 molecules are responsible for a destabilization of the immune network and the elimination of CD4+ T cells.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Striking inverse association of IgG-anti-Fab gamma antibodies and CD4 cell counts in patients with acquired immunodeficiency syndrome (AIDS)/AIDS-related complex.

The contribution of autoimmune phenomena to the pathogenesis of acquired immunodeficiency syndrome (AIDS) is poorly understood. We investigated the relationship between IgG-anti-Fab gamma autoantibodies and the main immunologic feature of AIDS, the decrease of CD4+ helper lymphocytes. Sera of 33 human immunodeficiency virus (HIV) infected (HIV+) hemophilia patients with AIDS/AIDS-related complex (ARC), 57 HIV+ patients without AIDS/ARC, 23 HIV-negative (HIV-) patients, and 76 healthy controls were tested for antibody activity against the Fab region of IgG. Patients with AIDS/ARC had significantly higher IgG-anti-Fab gamma activity than HIV+ patients without AIDS/ARC, HIV- patients, or controls (P less than .0001). A striking inverse association was found between IgG-anti-Fab gamma and CD4+ cell counts (r = -.69; P less than 10(-6)). Sequential testing in 16 AIDS/ARC patients showed that an increase in the IgG-anti-Fab gamma activity was invariably accompanied by a decrease in the CD4+ cell count. IgG-anti-Fab gamma antibodies may play an important role in the immunopathogenesis of AIDS.

AIDS-Related Complex↗
PubMed1992

An immunoglobulin-specific autoantibody occurring during alloimmunization suppresses the antibody response.

Our previous studies showed that a broadly reactive immunoglobulin G (IgG) anti-immunoglobulin (IgG-anti-Ig) autoantibody is induced during the immune response of LEW rats to BN blood cells. The present experiments analyze the immunoregulatory effect of this physiological autoantibody on antigen receptor-activated B cells in cell cultures. The results show that: (a) At 0.9 pg IgG-anti-Ig/10(6) B cells, an almost complete suppression of the antibody response is induced: we calculated that a few IgG-anti-Ig molecules are sufficient to suppress the antibody response of one B cell; (b) IgG-anti-Ig-induced B-cell suppression is dose-dependent; (c) IgG-anti-Ig suppresses B cells contained in their natural environment (mixed spleen cell population). These data demonstrate that the IgG-anti-Ig autoantibody is an extremely efficient regulatory molecule of the alloimmune response.

Animals↗