concanavalin-a and Hemophilia-A

Human immunodeficiency virus (HIV)-induced immune complex load on circulating CD4+ blood lymphocytes is associated with dysfunction and depletion of CD4+ lymphocytes and with increased monocyte/macrophage function. It was investigated whether HAART reduces both the viral load in plasma and the number of immune complex-coated CD4+ lymphocytes in the blood, and whether CD4+ counts are associated with viral load and/or immune complex load.. Twelve HIV+ hemophilia patients before and after conversion to HAART (group 1); eight HIV+ hemophilia patients without antiretroviral therapy (group 2). HIV-1 RNA copies in plasma using NASBA/Nuclisens kits; CD4+ lymphocytes coated in-vivo with immune complexes using flowcytometry on whole blood samples; in-vitro responses of immune complex-coated T lymphocytes in cell culture assays.. After conversion to HAART there was a significant reduction of viral load, CD4+ gp120+, CD4+ IgM+, and CD4+ IgG+ circulating blood lymphocytes and plasma neopterin, paralleled by a significant increase of CD4+ and CD8+ counts. The percentage of immune complex-coated CD4+ lymphocytes of converted patients was significantly associated with CD4+ counts, in-vitro responses to concanavalin A (Con A), pokeweed mitogen (PWM), phytohaemagglutinin (PHA), anti-CD3 and pooled allogeneic stimulator cells, and with plasma neopterin levels.. HAART reduces viral load and HIV-induced immune complex load on circulating CD4+ blood lymphocytes. The results of this study can be interpreted to suggest that HAART increases CD4+ lymphocyte counts in part by counteracting HIV-induced autoimmune phenomena.

Topics: Anti-HIV Agents; Antibodies, Anti-Idiotypic; Antigen-Antibody Complex; Autoantibodies; Autoimmunity; CD4-Positive T-Lymphocytes; Concanavalin A; Drug Therapy, Combination; Hemophilia A; HIV Envelope Protein gp120; HIV Infections; HIV Protease Inhibitors; Humans; Immunoglobulins; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Male; Mitogens; Reverse Transcriptase Inhibitors; RNA, Viral; Viral Load; Viremia

T-lymphocyte function, as expressed by polyclonal proliferation to lectin mitogens phytohaemagglutinin and concanavalin A, has been studied in a normal control population and three groups of haemophilic boys: group 1, HIV and HCV seronegative and treated only with a single heat-treated factor VIII (FVIII) concentrate; group 2, HIV seronegative but HCV seropositive; group 3, all HIV and HCV seropositive. Groups 2 and 3 have been previously treated with unheated and heated FVIII concentrate. Group 1 boys (HIV/HCV uninfected) showed no significant reduction in lymphocyte proliferation when compared with a control population. Group 2 and 3 boys showed an impaired response to these mitogens compared to group 1 boys and the control group. There was no relationship between FVIII concentrate received and proliferative response. The absence of immune modulation in haemophilic boys who have not acquired HIV and HCV infection implicates chronic blood-borne virus infections as the major contributory factors to impaired lymphocyte proliferative responses seen in haemophiliacs treated with large-pool concentrates. The presence of virus infections, such as HCV, may account for similar lymphocyte function abnormalities observed in previously described cohorts.

Topics: Adolescent; Child; Child, Preschool; Concanavalin A; Factor VIII; Follow-Up Studies; Hemophilia A; Hepatitis C; HIV Seropositivity; Humans; Immune Tolerance; Lymphocyte Activation; Male; Phytohemagglutinins; T-Lymphocytes

Concanavalin A (Con-A)-induced suppression of T cell proliferation was studied in 48 patients with severe hemophilia. Two groups of patients were defined according to the proliferative response when increasing numbers of Con A-induced cells were added to a constant number of phytohemagglutinin (PHA)-stimulated autologous T cells: In group A (60%) and in normal controls, higher suppression was achieved when more Con A-induced cells were added; in Group B, increasing numbers of Con A-induced cells produced no suppression of stimulated PHA-triggered proliferation. This effect could be corrected in Group B by inducing suppression in the presence of inhibitors of the oxidative metabolism of arachidonic acid. No correlation was found between the suppression profile and HIV-1 or HBV serology. Clinical evolution, as judged by signs and symptoms of AIDS related complex tended to be better in Group B than in Group A patients. It is suggested that decreased Con A-induced suppression in Group B may represent part of a normal regulatory process that involves products of arachidonic acid oxidative metabolism.

Topics: Adolescent; Adult; Concanavalin A; Hemophilia A; HIV Seropositivity; Humans; Lymphocyte Activation; T-Lymphocytes

This study was established to examine the longitudinal consequences of F VIII therapy on immune function in 24 patients with haemophilia A. Antibodies to the human immunodeficiency virus (HIV) were found in 15 of 16 patients with severe haemophilia and in 2 of 8 patients with mild disease. The principal clinical and immunological abnormalities were restricted to the HIV antibody-positive patients: T helper cell lymphopenia (less than 0.55 x 10(9)/l) in 10 patients, persistent glandular lymphadenopathy in 4 patients and depressed response to skin recall antigens in 7 of 9 HIV-positive patients tested. Although no extension of these immunological and clinical abnormalities developed in the 18-month period of monitoring, T helper cell counts and platelet counts were significantly lower in a group of patients with established long duration HIV seropositivity (since 1982/1983) in comparison with the remaining seropositive patients. This suggests that a progressive pathological process is associated with infection by this virus, but the factors which determine the long-term sequelae are still unknown.

Topics: Adolescent; Adult; Aged; Antibodies, Viral; B-Lymphocytes; Concanavalin A; Factor VIII; Hemophilia A; HIV Seropositivity; Humans; Hypersensitivity, Delayed; Lymphocyte Activation; Lymphocytes; Middle Aged; Platelet Count; Prospective Studies; Skin Tests; T-Lymphocytes, Helper-Inducer

Topics: Antigen-Antibody Complex; Complement C3; Complement C4; Concanavalin A; Hemophilia A; Hemophilia B; Humans; Immunity, Cellular; Immunoglobulin G; Lymphocyte Activation; T-Lymphocytes, Regulatory

In order to reveal the activity of polymorphonuclear neutrophil leukocytes (PMNL) representing the first step of defence against infections, measurements of chemiluminescence (CL) were performed in patients suffering from acquired immune deficiency syndrome (AIDS), lymphadenopathy, or hemophilia. In comparison with healthy controls, AIDS patients revealed significant reduction (about 50 per cent) of phagocytic, i.e. CL activity of neutrophils, which had been induced by Zymosan. Only part of the patients suffering from lymphadenopathy answered with decreased granulocyte activity on the application of Zymosan. If concanavalin A was used as stimulant of metabolic activity of PMNL-independently of phagocytosis-again AIDS and some of the lymphadenopathy patients showed a markedly reduced neutrophil response. In conclusion it should be stated that there is some evidence for at least two defects of cellular immunity associated with AIDS and to some extent, with AIDS-endangered homosexuals suffering from lymphadenopathy: first the defect of PMNL to answer to concanavalin A with increased metabolic activity, and secondly the defect of PMNL to start phagocytosis induced by Zymosan with a subsequent release of oxygen radicals which are measurable as chemiluminescence. The appraisal of granulocyte activity by means of measurements of chemiluminescence might become an additional criterion for AIDS diagnostics.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Anti-Infective Agents, Urinary; Concanavalin A; Drug Combinations; Hemophilia A; Humans; Immunoglobulins; Luminescent Measurements; Luminol; Lymphoproliferative Disorders; Male; Neutrophils; Phagocytosis; Sulfamethoxazole; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Zymosan

Scottish patients with haemophilia, most of whom had received no American factor VIII concentrate for over two years, were found to have immunological abnormalities similar to those in their American counterparts--that is, a reduced proportion of T helper cells, an increased proportion of T suppressor cells, and a reduced response to concanavilin A. Factor VIII from both the United States and Scotland severely inhibited the in vitro lymphocyte response to mitogens in patients and controls. The American and Scottish concentrates could not be distinguished in terms of either patient usage or their effect in vitro. These results argue against a disease vector specific to American blood products.

Topics: Adult; Aged; Concanavalin A; Factor VIII; Hemophilia A; Humans; Immunity, Cellular; Killer Cells, Natural; Leukocyte Count; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Scotland; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; United States

This study establishes a convenient method for screening plasma samples for abnormalities of the carbohydrate content of the factor VIII (FVIII) molecule. A radioimmuno-electrophoretic technique has been developed to quantitate the percentage binding of FVIII-related antigen (VIII-Ag) to the lectin concanavalin A (Con A). Plasma samples were electrophoresed through a strip of agarose containing Con A into agarose containing a mixture of unlabelled anti-FVIII and 125I-anti-FVIII where precipitant lines formed, the height of which was dependent upon the degree of VIII-Ag binding to Con A in the first gel. Using this system reduced binding of VIII-Ag to Con A was found in the plasma of 12 patients with moderate classical von Willebrand's disease (vWd), while the Con A binding of six haemophilia A patients fell within the normal range. The VIII-Ag in normal cryoprecipitate showed increased % binding to Con A while the VIII-Ag remaining in the cryo-supernate demonstrated reduced Con A % binding.

Topics: Antigens; Carbohydrates; Concanavalin A; Factor VIII; Hemophilia A; Humans; Immunoelectrophoresis, Two-Dimensional; von Willebrand Diseases

Topics: Blood Platelets; Cell Membrane; Chemical Precipitation; Chromatography, Gel; Concanavalin A; Cytosol; Factor VIII; Hemophilia A; Humans; Immunoelectrophoresis, Two-Dimensional; von Willebrand Diseases

Topics: Animals; Blood Coagulation Tests; Brain; Calcium Chloride; Concanavalin A; Culture Techniques; Fibroblasts; Hemophilia A; Humans; Mannose; Methylglycosides; Rabbits; Thromboplastin