Autoimmune Disease

Abdou et al. [22] reported that the binding of human anti-DNA antibodies to DNA could be blocked by autologous sera obtained from patients with SLE when their disease was in remission and by the F(ab')2 and Fab fragments derived from these sera. The inhibition of binding was interpreted as being due to the presence of anti-idiotypes in the inactive sera that reacted with the binding site of the anti-DNA antibodies present in the sera of patients when their disease was active. Additional findings extending this concept have also been presented [23].

Studies of anti-DNA and anti-F(ab')2 antibodies were performed by enzyme-linked immunosorbent assay (ELISA) in 51 patients with SLE [24], Patients with severe, uncontrolled disease showed high levels of anti-DNA and low levels of anti-F(ab')2 antibodies. Patients with quiescent SLE usually showed high levels of anti-F(ab')2 and low levels of anti-DNA antibodies. Isolated anti- F(ab')2 antibodies from autologous SLE remission serum or from the sera of unaffected siblings of SLE patients showed maximum inhibition in test systems using affinity-purified SLE anti-DNA antibodies reacting with single-stranded DNA.

In another study, it was demonstrated that specific anti-idiotypes can suppress the production of anti-DNA antibodies by peripheral blood mononuclear cells from active SLE patients [25], These authors have developed an ELISA system for measuring in vitro anti-DNA antibody production by peripheral blood mononuclear cells (PBMC) from patients with SLE. Using this technique, the PBMC from 74% of serologically active SLE patients produced levels of anti-DNA antibodies that were increased 2 SD above the mean of 18 ± 9 IU/ml for normal subjects.

Furthermore, the addition of 3-1, a monoclonal anti-idiotypic antibody that recognizes a cross-reactive determinant on anti-DNA antibodies, was shown to specifically inhibit anti-DNA production in vitro. This finding supports previous work that implicates antiidiotypes among the regulatory mechanisms that can control synthesis of anti-DNA antibodies in patients with SLE and previous studies reporting inhibition of idiotypic antibodies by the addition of anti-idiotypic in vitro cultures of human PBMC.

Zhou and Whitaker [26] raised a mAb of the IgGlIk isotype against human myelin basic protein (MBP) peptide acetyl 1-9. This mAb, termed F23, reacted with human MBP and human MBP peptides acetyl 1-9,1-14 and 1-44, but not with MBP peptides 10-19, 80-89, or 45-89. According to the guidelines of the molecular recognition theory, a complementary peptide to human MBP peptide 1-9 was synthesized and used to raise murine mAb with anti-Id activity. Two mAb anti-Id, F25F7 and F25C8, both of the IgM//<: isotype, were selected for further study.

The cross-reactive anti-Id suppressed antibody secretion of Id-producing hybridoma cells in an Id-specific manner, and kinetic studies suggest an intracellular mechanism for the suppression. These cross-reactive Id among antibodies to different MBP peptides imply that the same V region genes of k-L chains are involved in the selection of antibodies to an autoantigen, like MBP, and may play a role in the modulation of immune responses against MBP in certain inflammatory demyelinating diseases [26].

In another study [24], rabbit anti-idiotypic antibodies to human rheumatoid factor (RF) autoantibodies were isolated by affinity chromatograpy on rabbit antihuman IgG Fc sepharose 4B. The anti-idiotypic antibodies bore the "internal image" of the antigen, human IgG. They reacted specifically with multiple human monoclonal and polyclonal IgM-RF, independent of any particular light or heavy chain amino acid sequence. The anti-idiotypes did not react with IgM or IgG proteins lacking RF activity. The experiments in this study [27] determined the potential of the "internal image" antibodies to modulate in vitro lymphocyte functions.

The addition of anti-idiotypic antibody to peripheral blood mononuclear cell cultures from patients with rheumatoid arthritis elicited lymphocyte proliferation, but not RF synthesis. The antibody did not induce the proliferation of lymphocytes from a normal individual. Moreover, the anti-idiotype specifically suppressed IgM-RF secretory responses when preincubated with B cells before co-culture with autologous pokeweed mitogen-activated T cells. This study showed that the anti-idiotypic antibodies with the "internal image" of antigen are capable of interacting with B-cell receptors in an antigen-restricted manner, and possess specific immunomodulatory properties

Takeuchi et al. [28], further studied the effect of anti-idiotypic antibody on the in vitro production of RF in rheumatoid arthritis patients with cross-reactive idiotypic determinants. Anti-idiotypic antibodies were developed against monoclonal RF (Kam-RF) by a cell fusion procedure. These antibodies were idiotype-specific. The anti-idiotypic antibody strongly suppressed the in vitro production of RF by lymphocytes from unrelated rheumatoid arthritis patients with cross-reactive idiotypes. These results indicate that anti-idiotype antibody may influence the regulation of RF production in patients with rheumatoid arthritis

Kojima et al. [29] have reported on the suppression of in vitro human antithyroglobulin antibody secretion in Epstein-Barr virus transformed B lymphocytes by private and cross-reactive anti-idiotypic antibodies.

It was suggested that interactions between idio-type and anti-idiotype may play a role in the immune regulation of human-chronic thyroiditis [29].

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