concanavalin-a and Spondylitis--Ankylosing

To determine the lymphoproliferative response to the 30-kDa protein (p30) of Salmonella typhimurium in patients with ankylosing spondylitis (AS).. Lymphoproliferative response was determined in peripheral blood mononuclear cells (PBMCs) from 30 patients with AS and 40 healthy subjects. Cells were cultured with concanavalin A (Con A), a crude lysate of S. typhimurium (StCL), or p30. Lymphoproliferation was measured by the MTT assay.. Our data show that the mitogenic response to Con A was similar in both groups studied; however, the lymphoproliferative response to StCL and p30 was statistically higher in AS patients than in healthy subjects.. Our data strongly suggest that S. typhimurium, and particularly p30, are associated with AS.

Topics: Adult; Bacterial Proteins; Concanavalin A; Female; Humans; Immunity, Cellular; Lymphocytes; Male; Middle Aged; Salmonella Infections; Salmonella typhimurium; Spondylitis, Ankylosing

HLA-B27 is implicated in the pathogenesis of spondylarthritis (SpA), yet the molecular mechanisms are incompletely defined. HLA-B27 misfolding has been associated with endoplasmic reticulum stress and activation of the unfolded protein response (UPR) in macrophages from HLA-B27/human beta(2)-microglobulin-transgenic (B27-transgenic) rats. This study was performed to assess the mechanisms that drive activation of the HLA-B27-induced UPR and to determine whether splenocytes respond in a similar manner.. Splenocytes were isolated and bone marrow macrophages were derived from B27-transgenic and wild-type rats. Cells were treated for up to 24 hours with cytokines that induce class I major histocompatibility complex expression. HLA-B27 expression and misfolding were assessed by real-time reverse transcription-polymerase chain reaction, flow cytometry, and immunoblotting. Activation of the UPR was measured by quantifying UPR target gene expression and X-box binding protein 1 messenger RNA (mRNA) splicing.. HLA-B27 mRNA up-regulation was accompanied by a dramatic increase in the accumulation of misfolded heavy chains and preceded robust activation of the UPR in macrophages. When macrophages were treated with various cytokines, the magnitude of the UPR correlated strongly with the degree of HLA-B27 up-regulation. In contrast, B27-transgenic splenocytes exhibited only low-level differences in the expression of UPR target genes after exposure to interferon-gamma or concanavalin A, which resulted in minimal HLA-B27 up-regulation.. These results suggest that HLA-B27-associated activation of the UPR in macrophages is attributable to the accumulation of misfolded heavy chains, and that certain cell types may be more susceptible to the effects of HLA-B27 misfolding. Strategies that eliminate HLA-B27 up-regulation and/or the accumulation of misfolded heavy chains may be useful in evaluating the role of these events in the pathogenesis of SpA.

Topics: Animals; Basic-Leucine Zipper Transcription Factors; Bone Marrow Cells; Cell Line; Concanavalin A; DNA-Binding Proteins; HLA-B27 Antigen; Interferon-gamma; Macrophages; Molecular Chaperones; Neoplasm Proteins; Organisms, Genetically Modified; Protein Folding; Rats; Regulatory Factor X Transcription Factors; Reverse Transcriptase Polymerase Chain Reaction; RNA Splicing; Spleen; Spondylitis, Ankylosing; Transcription Factors; Up-Regulation

Microheterogeneity of acute phase proteins frequently differs in acute and chronic types of inflammation. However, it is unknown whether these changes depend on the duration of the inflammation in a given disease. We therefore investigated the microheterogeneity of alpha 1-acid glycoprotein (AGP) in sera from patients with acute and chronic bacterial infection in comparison to rheumatoid arthritis and ankylosing spondylitis. In acute bacterial infection Con A-reactivity of AGP was significantly elevated. By contrast, AGP in chronic bacterial infection showed the same glycosylation pattern as rheumatoid arthritis and ankylosing spondylitis being characterized by a decreased reactivity to Con A. Serial measurements in individual patients with bacterial infections showed a transition from the initially elevated to decreased reactivity to Con A as the disease became chronic.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Bacterial Infections; C-Reactive Protein; Chronic Disease; Concanavalin A; Female; Glycosylation; Humans; Immunoelectrophoresis, Two-Dimensional; Male; Middle Aged; Orosomucoid; Spondylitis, Ankylosing; Staphylococcal Infections; Streptococcal Infections

Despite chronic inflammation and the presence of hypergammaglobulinemia, rheumatoid factor (RF) is rarely found in the blood of patients with ankylosing spondylitis (AS). We used ELISA to compare spontaneous and pokeweed mitogen (PWM)-induced IgG, IgM and IgM rheumatoid factor (IgM-RF) production in normals and in patients with rheumatoid arthritis (RA) and AS. The IgG and IgM synthesis in these three groups did not differ. However, the IgM-RF level in PWM-induced mononuclear cell cultured supernatants of AS was significantly decreased, compared with normal and RA patients. Furthermore, mixing experiments by co-culture of normal T or B cells with patient's B or T cells in the presence of PWM revealed a deficiency of the helper T cell function in patients with AS. These results illustrate the cellular mechanism of the seronegativity of the rheumatoid factor in patients with ankylosing spondylitis.

Topics: Arthritis, Rheumatoid; Cells, Cultured; Concanavalin A; Humans; Immunoglobulin G; Immunoglobulin M; Pokeweed Mitogens; Rheumatoid Factor; Spondylitis, Ankylosing; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Topics: Arthritis, Rheumatoid; C-Reactive Protein; Carbohydrates; Concanavalin A; Genetic Variation; Humans; Immunoelectrophoresis; Lupus Erythematosus, Systemic; Orosomucoid; Rheumatic Diseases; Spondylitis, Ankylosing

The T-cell mediated immunity in 21 patients with seronegative spondarthritis was tested with mitogens PHA, PWM, Con-A and MLC, and found to be reduced except when tested with Con-A. The patients were then treated with levamisole or placebo for 12 weeks in a double-blind trial. During treatment the T-cell responses normalized in both groups, and it is concluded that the enhanced response is independent of levamisole. Earlier we reported clinical improvement in levamisole treated patients and the data of the present study suggest that the effect of levamisole occurs locally in the inflamed tissues.

Topics: Adult; Arthritis, Reactive; Concanavalin A; Double-Blind Method; Female; Humans; Levamisole; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Male; Middle Aged; Phytohemagglutinins; Pokeweed Mitogens; Spondylitis, Ankylosing; T-Lymphocytes

Topics: Adolescent; Adult; Cells, Cultured; Concanavalin A; Humans; In Vitro Techniques; Lymphocyte Activation; Middle Aged; Phytohemagglutinins; Spondylitis, Ankylosing; Stimulation, Chemical; T-Lymphocytes

We have studied the in vitro antibody response to a hapten of peripheral blood lymphocytes from 26 patients with rheumatoid arthritis and 7 ankylosing spondylitis. These patients had never received immunosuppressor drugs before or corticosteroids during the month before the test. They had failed to receive aspirin or non-steroid anti-inflammatory drugs for 72 hours before blood sampling. The control groups included respectively 38 healthy subjects and 24 patients hospitalized for non inflammatory disease. The antibody response of ankylosing spondylitis patients is comparable to that of controls ; on the opposite the response of patients with rhumatoid arthritis is significantly depressed in comparison with the three other groups. The weak response of lymphocytes in arthritis is not due to increased cell death in culture or to modified kinetics of the antibody response or to the appearance of a IgG secondary type response or a in vivo pre-activation. The lymphocytes of arthritis patients do not inhibit the response of normal lymphocytes when they are co-cultured. The observed response is identical to that obtained when control patient lymphocytes are co-cultured with normal lymphocytes. The function of suppressor T cells induced by Con A seems normal in spondylitis and arthritis.

Topics: Adult; Aged; Antibody Formation; Arthritis, Rheumatoid; Cells, Cultured; Concanavalin A; Female; Humans; Lymphocytes; Male; Middle Aged; Spondylitis, Ankylosing; T-Lymphocytes, Regulatory; Trinitrobenzenes