concanavalin-a and Arthritis--Juvenile

Agarose based affinity immunoelectrophoresis with free concanavalin A (Con-A) as ligand was used to examine the microheterogeneity of alpha 1-acid glycoprotein in sera of patients with systemic onset juvenile rheumatoid arthritis (JRA) and acute bacterial infections. In JRA, a decreased proportion of Con-A reactive alpha 1-acid glycoprotein variants was found when compared to healthy control. In contrast, acute bacterial infection showed an increased reactivity. Investigation of glycosylation may be useful in the differential diagnosis of systemic onset JRA and acute bacterial infection.

Topics: Acute Disease; Arthritis, Juvenile; Bacterial Infections; C-Reactive Protein; Child; Child, Preschool; Concanavalin A; Diagnosis, Differential; Glycosylation; Humans; Immunoelectrophoresis; Ligands; Orosomucoid

The purpose of this study was to analyze T suppressor cell function in juvenile rheumatoid arthritis (JRA). JRA is a chronic inflammatory childhood disease of unknown etiology that is characterized by arthritis and immunoregulatory abnormalities. T suppressor cell precursors (CD8+, CD28-) were purified from the peripheral blood of 24 JRA patients, using a combination of monoclonal antibodies. These cells were treated with histamine or concanavalin A, agents that are known to induce suppressor activity. They were also tested for their ability to inhibit the proliferative response of autologous T cells to phytohemagglutinin. In some experiments, the accumulation of intracellular cAMP following histamine treatment was also measured. Twelve of 13 patients with clinically active JRA showed abnormal histamine-inducible T suppressor cell function, characterized by the failure of CD8+, CD28- T cells to mediate any detectable suppression. The failure of these cells to accumulate intracellular cAMP after histamine treatment was observed in 5 of 5 patients tested who had active disease. In contrast, 11 of 11 patients with clinically inactive JRA, 5 of 5 patients with cystic fibrosis, and 9 of 9 pediatric control subjects had normal histamine- and concanavalin A-inducible T suppressor cell function, and a normal cAMP response to histamine. These results suggest that patients with clinically active JRA have a reversible defect in T suppressor cell function that is associated with a failure of T suppressor cell precursors to accumulate intracellular cAMP following their exposure to selected immune stimuli.

Topics: Adolescent; Antibodies, Monoclonal; Arthritis, Juvenile; Child; Concanavalin A; Cyclic AMP; Female; Histamine; Humans; Male; T-Lymphocytes, Regulatory

The presence of hypergammaglobulinemia and various circulating autoantibodies in children with polyarticular juvenile rheumatoid arthritis (JRA) implies an immunoregulatory disorder. We report here experiments planned to elucidate the underlying cellular aberrations in this disease. Twelve children with polyarticular JRA were studied. Percentages of Leu-1, Leu-2, and Leu 3 T cells were comparable to those of normal individuals. Immunofluorescent double staining studies demonstrated elevated numbers of activated (DR+) T cells of both Leu-2 and Leu-3 phenotype. B cells characterized both phenotypically (Leu-12) and functionally (as spontaneous plaque-forming cells, PFC) were elevated. In vitro PFC responses to pokeweed mitogen (PWM) and Epstein-Barr virus (EBV) were diminished. The levels of concanavalin A-induced suppressor cells of the PWM-stimulated PFC responses were comparable to control values. In contrast, the EBV-associated suppressor T cells were significantly impaired in both EBV-seropositive and EBV-seronegative patients. These studies indicate that peripheral blood B-cell activity is abnormal in polyarticular JRA. Defective T-cell responses in vitro suggest that this may be due to disruption of normal regulatory circuits between B and T cells and may contribute to the pathogenesis of this disease.

Topics: Antibody Formation; Antigens, Differentiation, T-Lymphocyte; Arthritis, Juvenile; B-Lymphocytes; Child; Concanavalin A; Herpesvirus 4, Human; HLA-DR Antigens; Humans; Leukocytes, Mononuclear; Rheumatoid Factor; T-Lymphocytes; T-Lymphocytes, Regulatory

We studied the cellular immune responses in 10 patients with systemic form of juvenile rheumatoid arthritis. The numbers of peripheral T lymphocytes and their helper/inducer and cytotoxic/suppressor subpopulation were within normal levels. Activated T lymphocytes (DR+) were slightly increased but not at statistically significant levels. In contrast to the T cells, B lymphocytes were increased; both the percentage of B cells (B1+) and the number of cells spontaneously secreting IgG, IgA, and IgM were increased. Stimulation of peripheral mononuclear cells in vitro with pokeweed mitogen induced poor plaque-forming cell responses, which were partially improved upon removal of monocytes. The presence of concanavalin A in the cultures led to complete suppression. We conclude that patients with systemic JRA are characterized primarily by B-cell rather than T-cell abnormalities.

Topics: Adolescent; Arthritis, Juvenile; B-Lymphocytes; Child; Child, Preschool; Concanavalin A; Female; Hemolytic Plaque Technique; Humans; Immunity, Cellular; Lymphocyte Activation; Male; Pokeweed Mitogens; T-Lymphocytes

We have investigated the cellular composition of 108 consecutive samples of synovial fluid from patients with Juvenile Chronic Arthritis (JCA), Rheumatoid Arthritis (RA) and Osteoarthritis (OA). Particular emphasis was placed upon the enumeration of cells with dendritic morphology and the study of their in vitro function. Whilst the cellularity of the synovial fluids varied by a factor of greater than 100 within patient groups, the fluids obtained from patients with inflammatory arthritis (JCA & RA) were more cellular than those from patients with non-inflammatory arthritis (OA). This was also noted with respect to both the number and proportion of dendritic cells. The dendritic cells stimulated allogeneic mixed leucocyte reactions, and enhanced mitogenic responses of peripheral blood lymphocytes when present in numbers as low as 1% of the total mononuclear cells. Syngeneic stimulation of blood lymphocytes by similar numbers of dendritic cells was usually negative. However, occasionally there was a marked syngeneic stimulation, which may be evidence for the presentation of antigen by dendritic cells within the arthritic joint.

Topics: Arthritis; Arthritis, Juvenile; Concanavalin A; Humans; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphoid Tissue; Synovial Fluid

We studied the suppressor cell activity induced by concanavalin A (Con A) in 9 patients with acute febrile juvenile rheumatoid arthritis (JRA). The suppressor activity of JRA patients was higher than that of normal controls. However, the activity was significantly reduced by treating Con A-activated cells with mitomycin C (MMC) (P less than 0.05). On the other hand, the suppressor activity of normal controls and systemic lupus erythematosus (SLE) patients was not affected by MMC treatment. Two of 5 SLE patients showed low activity even before MMC treatment. The addition of the culture supernatant of Con A-stimulated peripheral blood mononuclear cells from a normal donor restored the induction of suppressor activity of JRA which was decreased by MMC treatment. The results indicated that patients with acute febrile type of JRA had reduced MMC resistant suppressor cell activity and that this was due to a defect in the ability of the cells to produce soluble factors needed to induce MMC resistant suppressor cells.

Topics: Arthritis, Juvenile; Autoantibodies; Concanavalin A; Humans; Lupus Erythematosus, Systemic; Lymphocyte Activation; Reference Values; T-Lymphocytes, Regulatory

The presence of hyperimmunoglobulinaemia and antinuclear antibodies in patients with juvenile chronic arthritis (JCA) suggests a possible role for immunoregulatory abnormalities in the pathogenesis of the disease. This is further supported by the demonstration in the sera of such patients of an autoantibody active against a suppressor inducer T cell subset. To identify immunoregulatory defects in JCA, a method of measuring concanavalin A (Con A)-inducible lymphocyte suppression of IgG production in vitro has been established. Peripheral blood mononuclear cells were cultured in the presence of either medium alone, pokeweed mitogen (PWM), Con A, or PWM together with Con A. IgG present in culture supernates at 8 days was measured by a double-antibody radioimmunoassay. Spontaneous IgG synthesis by lymphocytes by both patients and child controls was found to be more than double that of lymphocytes from adult control subjects. However, lymphocytes of children (patients or controls) did not show stimulation of IgG production in the presence of PWM. Con A-induced suppression of spontaneous IgG synthesis was reduced compared to adult controls in both patients (p less than 0.02) and child controls (p less than 0.05). Con A-induced suppression of IgG synthesis in the presence of PWM was also reduced compared to adult controls in both patients (p less than 0.01) and child controls (p less than 0.01) but was also reduced in the patient group compared to the child controls (p less than 0.01). Thus, spontaneous IgG synthesis in children is increased compared to adults, and IgG-producing cells appear less subject to regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Arthritis, Juvenile; Aspirin; Child; Citrates; Citric Acid; Concanavalin A; Humans; Immunoglobulin G; Lymphocyte Activation; Pokeweed Mitogens; T-Lymphocytes; Thymidine

Concanavalin-A-induced suppressor cell activity was investigated in 63 patients with a definite diagnosis of juvenile rheumatoid arthritis. Peripheral blood lymphoid cells from these patients did not have the same ability as cells from normal individuals to suppress the proliferative response of autologous cells, responding to phytohaemaglutinin, Candida albicans antigen, or allogeneic cells. No correlation was found between suppressor activity, disease activity, or number of joints involved. Nor was there any significant association between decreased suppressor cell activity and HLA-A, -B, -C, -D antigens, although there was a tendency towards association between decreased suppressor cell activity and HLA-B27.

Topics: Adolescent; Adult; Arthritis, Juvenile; Child; Child, Preschool; Concanavalin A; Dose-Response Relationship, Immunologic; Female; Genes, MHC Class II; HLA Antigens; HLA-B Antigens; HLA-C Antigens; HLA-DR Antigens; Humans; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Male; Middle Aged; Phytohemagglutinins; T-Lymphocytes, Regulatory

Topics: Adolescent; Adult; Arthritis, Juvenile; Child; Child, Preschool; Concanavalin A; Cytotoxicity, Immunologic; Female; Genetic Linkage; HLA Antigens; HLA-B27 Antigen; Humans; Immunity, Cellular; Lymphocyte Activation; Male; Mitogens; Phytohemagglutinins; Pokeweed Mitogens; Staphylococcus aureus

The human inducer (T4(+)) and reciprocal cytotoxic/suppressor (T5(+)/T8(+)) subsets have been defined by monoclonal antibodies. In the present study, we examined the relationship of naturally occurring anti-T cell autoantibodies found in patients with active juvenile rheumatoid arthritis (JRA) to these subsets. In one approach, normal T cells were treated with anti-T4 or anti-T8 to eliminate the corresponding subset of cells and then analyzed for reactivity with JRA sera. It was found that JRA sera were reactive with only 15% of an enriched cytotoxic/suppressor population, whereas they reacted with 37% of an enriched inducer population. In reciprocal studies, JRA(+) T cells were eliminated with JRA sera and complement and the residual T cells (JRA(-)) reacted with monoclonal antibodies and indirect immunofluorescence on a fluorescence-activated cell sorter. As expected, the JRA sera and complement treatment of unfractionated T cells markedly diminished the T4(+) subset, whereas there was a concomitant increase in T cells reactive with anti-T5 and anti-T8. A similar diminution in T4(+) T cells was found in the circulating peripheral T cell compartment of patients with active JRA who possessed the JRA antibody. Functional studies demonstrated that removal of the JRA(+) population of T cells diminished phytohemagglutinin and soluble antigen proliferative responses, both of which were previously shown to be functions of T4(+) T cells. More importantly, in the absence of JRA(+) T cells, pokeweed mitogen-stimulated immunoglobulin production was markedly enhanced, despite the concomitant increase in T5(+)/T8(+) cytotoxic/suppressor cells. These results suggest that the JRA serum may define a Qal-like antigen found predominantly on the human inducer population which could activate suppressor and/or other feedback regulatory cells.

Topics: Antigens, Surface; Arthritis, Juvenile; Autoantibodies; Concanavalin A; Humans; Lymphocyte Activation; Lymphocyte Cooperation; T-Lymphocytes; T-Lymphocytes, Regulatory

Suppressor cell activity was investigated in peripheral blood lymphocytes from twenty patients with rheumatoid arthritis (RA) and twenty patients with juvenile rheumatoid arthritis (JRA) using a concanavalin A/mixed lymphocyte culture assay. The mean suppression in the RA patients was slightly reduced compared with the suppressor cell activity in adult controls (25 +/- 5% suppression compared with 37 +/- 5%; P less than 0.05, Student's t test), whereas the JRA patients had normal suppressor cell activity (mean 46 +/- 5% versus 43 +/- 5% in healthy children matched for age and sex). The RA patients had normal proportions of T-cell subpopulations, 13.3% T gamma cells and 49.8% T mu cells, compared with 13.8% and 58.0% in controls. The JRA patients, however, had a significantly reduced mean percentage of T gamma cells, 6.6%, compared with 13.8% in healthy children (P less than 0.05, Mann-Whitney U-test). The mean percentage of T mu cells was 53.7%, versus 56.2% in the controls. The relation between suppressor cell activity and suppressor cells enumerated by membrane markers is discussed.

Topics: Adult; Arthritis, Juvenile; Arthritis, Rheumatoid; Cells, Cultured; Concanavalin A; Humans; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Lymphocyte Culture Test, Mixed; T-Lymphocytes; T-Lymphocytes, Regulatory

Synovial lymphocytes eluted by enzyme treatment from eleven patients with rheumatoid arthritis (RA) were investigated for the presence of concanavalin A (Con A)-activated suppressor cell activity as compared with that of peripheral blood lymphocytes of twenty normal donors. In addition, two patients with psoriatic arthritis and juvenile rheumatoid arthritis (JRA) were also investigated. Synovial lymphocytes from the eleven RA patients showed a mean augmentation of 28 +/- 13.30, and thus clearly lacked suppressor activity, whereas the mean suppression in the lymphocytes from the twenty normal donors was 13 +/- 14.40. Synovial lymphocytes from one patient with JRA and one with psoriatic arthritis showed a normal suppressor activity.

Topics: Arthritis, Juvenile; Arthritis, Rheumatoid; Concanavalin A; Humans; Lymphocyte Activation; Lymphocytes; Synovial Membrane; T-Lymphocytes, Regulatory

Thirty patients with juvenile rheumatoid arthritis (JRA) were compared to an age-matched control population with respect to lymphocyte transformation by the mitogens Concanavalin A, Phytohemagglutinin-P, Pokeweed and Lipopolysaccharide, as well as for the relative frequency of E-rosette and Ig-bearing cells in peripheral blood. The data were analysed according to sex, age of onset, mode of onset and disease activity. Lymphocytes from patients with a pauciarticular pattern of onset of JRA responded to mitogens in a similar fashion as normal volunteers, whereas lymphocytes from patients with both a polyarticular and Still's mode of onset had a diminished response to the mitogens. However, this reduction was noteworthy only during periods of disease activity; during periods of remission, lymphocytes from the patients responded similarly to lymphocytes from normals. In contrast to this reduction in mitogen stimulation in these subgroups of patients with JRA, all patients with JRA--irrespective of disease activity or mode of onset--were similar to controls with respect to the percentage of E-rosette and Ig-bearing cells. These alterations in mitogen responsiveness could not be attributed to therapy. Finally, the abnormalities of lymphocyte transformation in patients with polyarticular and Still's mode of onset represent secondary features of disease and are not due to a generalized predisposition or abnormality of cell mediated immunity.

Topics: Adolescent; Arthritis, Juvenile; Child; Child, Preschool; Concanavalin A; Female; Humans; Lipopolysaccharides; Lymphocyte Activation; Male; Mitogens; Phytohemagglutinins; Pokeweed Mitogens; Receptors, Antigen, B-Cell; Rosette Formation; Thymidine

Synovial tissues from 11 patients with juvenile rheumatoid arthritis were investigated. The elution of lymphocytes was performed according to a procedure previously described for synovial tissue of adult rheumatoid arthritis patients (1). The T lymphocytes were pre dominant (mean: 71%) in all cell suspensions studied, whereas the average proportion of B lymphocytes was 4%. In addition, Fc-receptor-bearing lymphocytes were demonstrable (mean: 8%). Transformation of the lymphocytes was induced by the unspecific mitrogens phytohemagglutinin, pokeweed mitogen, and concanavallin A, whereas antigens such as ppd and candida albicans antigen were usually ineffective.

Topics: Adolescent; Adult; Antigens, Fungal; Arthritis, Juvenile; B-Lymphocytes; Binding Sites, Antibody; Candida albicans; Child; Child, Preschool; Concanavalin A; Female; Humans; Immunoglobulin Fc Fragments; Lectins; Lymphocyte Activation; Lymphocytes; Male; Synovial Membrane; T-Lymphocytes; Tuberculin