O. Hosono

Thrombotic thrombocytopenic purpura in two patients with systemic lupus erythematosus: clinical significance of anti-platelet antibodies.

Thrombotic thrombocytopenic purpura (TTP) is a clinical syndrome of unknown etiology and has a high mortality rate due to disseminated platelet thrombi. However, the mechanism of platelet agglutination is not understood. Although an immunological mechanism has been suggested as the basis for the pathogenesis of TTP, any possible immune-mediated etiology remains unclear. The association of TTP with systemic lupus erythematosus (SLE) affords a unique opportunity to study such possibilities, because SLE is a prototype of autoimmune disease. This report describes two patients with SLE who developed TTP. The development of anti-platelet antibodies is one possible immunological mechanism for platelet agglutination in patients with SLE complicated by TTP. More importantly, patient J.Y., who had anti-platelet antibodies, responded dramatically to high doses of prednisolone.

CCA [N-(2-carboxyphenyl)-4-Chloroanthranilic acid disodium salt], a newly developed immunomodulating drug, suppresses T-cell activation by acting on macrophages

The cellular mechanism of action of a newly developed drug, CCA,N-(2-carboxyphenyl)-4-chloroanthranilic acid disodium salt, on PHA-, autologous mixed lymphocyte reaction (AMLR)-, and phorbol myristate acetate (PMA)-stimulated T-cell proliferation was investigated. Addition of 50 μg of CCA per milliliter suppressed PHA- and AMLR-stimulaled T-cell proliferation. In contrast. CCA failed to suppress PMA-stimulated macrophage-depleted T-cell proliferation. After treatment of T cells or macrophages with CCA for 12 h, recombined T cells and macrophages were stimulated with phytohemagglutinin. [3H]Thymidine incorporation by T cells was suppressed when macrophages but not T cells were treated with CCA. These results indicate that CCA suppresses T-cell proliferation by acting on macrophages. The mechanism involved in this suppression of CCA was due to the loss of Ia antigen on macrophages and the loss of interleukin-1 (IL-1) secretion from macrophages.

Defects of Autologous Mixed Lymphocyte Reaction‐Activated Immunoregulatory T Cells in Patients with Systemic Lupus Erythematosus

The present study was undertaken to determine the nature of the immunoregulatory T‐cell defect after autologous mixed lymphocyte reaction (AMLR) activation in patients with systemic lupus erythematosus (SLE). Although AMLR was decreased in patients with SLE compared with normals, there was no difference in major proliferative cells (T4 cells and T4+JRA+ subset) in response to AMLR. Functional activity of AMLR‐stimulated T4 subsets in patients with SLE and normals was examined in helper and suppressor/inducer assay, using pokeweed mitogen (PWM)‐driven IgG synthesis. The T4+JRA− (helper) subset from SLE patients showed no greater activity than normals. However the T4+JRA+ (suppressor/inducer) subset from SLE patients showed decreased suppression induction compared with normals. This defect in the suppressor/inducer function was demonstrated even in patients with inactive SLR or in remission.

The Presence of Anti‐Protein A Antibodies in Patients with Rheumatoid Arthritis

Sixteen patients with rheumatoid arthritis (RA) were examined for the presence of anti‐protein A antibodies. The F(ab′)2 preparations from five RA patients showed significant binding lo IgG‐free protein A on ELISA. The protein A binding was further examined by immunoblotting. The F(ab′)2 preparations of high protein A‐binding protein gave A specific reaction with IgG‐free protein A on nitrocellulose paper. This demonstrates the presence of anti‐protein A antibodies in patients with RA. Those RA patients with anti‐protein A antibodies had more active disease as judged by the Lansburys activity index. The level of serum rheumatoid factor (RAHA) was significantly higher in patients with anti‐protein A antibodies than in those without anti‐protein A antibodies.

Suppression of in vitro production of anti-U1-ribonucleoprotein antibody by monoclonal anti-idiotypic antibody to anti-U1-ribonucleoprotein antibody

We produced monoclonal anti‐idiotypic antibody against immunoaffinity purified anti‐U1‐ribonucleoprotein (RNP) antibody from a patient (K.T.), by the cell fusion procedure. The specificity of monoclonal anti‐idiotypic antibody (IgG1, x) was determined by inhibition studies. With the monoclonal anti‐idiotypic antibody, cross‐reactive idiotypes on anti‐U1‐RNP antibodies from unrelated patients with anti‐U1‐RNP antibody was detected in 57% of the samples. The anti‐idiotypic antibody specifically suppressed the in vitro production of anti‐U1‐RNP antibody by lymphocytes from the patient K T., and unrelated patients with a cross‐reactive idiotype, in whom idiotype‐reactive T cells were demonstrated. The results indicate that anti‐idiotypic antibody may modulate the regulation of in vitro anti‐U1‐RNP antibody production.

Cellular regulation of anti-nRNP antibody synthesis is different from that of anti-DNA antibody synthesis in patients with systemic lupus erythematosus.

SummaryThe cellular regulation of anti-nuclear ribonucleoprotein (nRNP) antibody synthesis in patients with systemic lupus erythematosus (SLE) was examined and compared with that of anti-double-stranded DNA (dsDNA) antibodies. In vitro antibody production by lymphocytes from SLE patients with antibodies to either dsDNA or nRNP alone was measured using dsDNA-specific and nRNP-specific solid-phase radioimmunoassays (RIA). Lymphocytes of SLE patients with only anti-dsDNA antibodies and normal individuals failed to synthesize anti-nRNP antibody with or without nRNP stimulation. In contrast, lymphocytes from SLE patients with anti-nRNP antibody alone in their sera synthesized in vitro a large amount of anti-nRNP antibody with or without nRNP stimulation. Experiments with reconstituted autologous lymphocytes indicated that B cells and T cells were required for anti-nRNP antibody synthesis. As expected, helper function for antibody synthesis by autologous B cells resided in the T4-cell population and suppressor function in the T8-cell population. T8 cells from SLE patients with anti-nRNP antibody alone suppressed anti-nRNP antibody synthesis by autologous B cells irrespective of clinical activity. This is in contrast to anti-dsDNA antibody production, which was not suppressed by autologous T8 cells. These results indicate that the cellular regulation of anti-nRNP antibody synthesis in SLE is different from that of anti-dsDNA antibody syntheis. Increased anti-nRNP antibody synthesis may be due to increased T4-helper cell function rather than defective T8-suppressor function.