PubMed · 7019598
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P J Caballero Vallés. 1981-04-10. [Rheumatoid factor].. https://pubmed.ncbi.nlm.nih.gov/7019598/
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Anti-idiotype of (natural) autoantibodies participate in the regulation of autoantibodies, their idiotypes. Focusing on an idiotype/anti-idiotype pair embedded in an environment such as the central immune system, we start with the experimental fact that the level of anti-idiotypes is low in autoimmune patients but high in healthy individuals, and present a quantitative model. This is then used to develop an adaptive control strategy that induces a transition back to the tolerant, healthy, state and thus offers a vista of treating autoimmune diseases caused by the failure of idiotypic control of autoreactive B cells. The idea is to introduce an antigen or anti-idiotype that binds to the autoantibodies with high affinity, and to determine whether or not a fixed dose is to be injected depending on the autoantibody titer exceeding or not exceeding a threshold. Quantitative criteria are provided. The procedure is the more adaptive in that monitoring the autoantibody titer need only happen every x-th day where x can greatly exceed one. Adaptive control turns out to be robust. The arguments presented here also give a quantitative explanation of why the antigen-autoantibody interaction has to be specific so as to induce a backward transition and why an IVIg treatment therefore does not lead to a permanent improvement.
BACKGROUND: IL-4 modulates the synthesis of IgE, the expression of CD23, and the release of 15(S)-hydroxyeicosatetraenoic (15[S]-HETE). OBJECTIVE: We evaluated the release of 15(S)-HETE by IL-4-stimulated monocytes and verified whether the observed increase in 15(S)-HETE release after passive sensitization and anti-IgE challenge of IL-4-treated monocytes was secondary to an increased CD23 expression. METHODS: Human monocytes were incubated for 24, 48, and 72 hours with IL-4 (10 ng/mL) with or without an IgE-anti-IgE stimulation. We evaluated CD23 expression by immunocytochemistry and 15(S)-HETE release by HPLC and RIA. To prove that the increase in 15(S)-HETE release was due to the effect of IL-4 on CD23, we performed experiments with an anti-CD23 blocking mAb. RESULTS: CD23 expression and 15(S)-HETE release were significantly increased by IL-4, reaching a peak after 72 hours (P <.02). After passive sensitization with human IgE and anti-IgE challenge, IL-4-stimulated monocytes released higher amounts of 15(S)-HETE than IL-4-unstimulated monocytes (P <.02). Pretreatment with the anti-human B-cell CD23 MHM6 mAb caused a dose-dependent inhibition of 15(S)-HETE release. CONCLUSIONS: This study shows that immunologic challenge of IL-4-treated, passively sensitized monocytes results in a CD23-dependent additional increase of 15(S)-HETE release, indicating the presence of a synergistic effect of IL-4 on CD23 expression and 15(S)-HETE production.
In accord with the original approach that we proposed, catalytic antibodies may be produced by using the anti-idiotypic pathway according to antigen/antibody complementarity rules. The generation and screening of the idiotypic Ab1, the central point on which are anchored the interactions with both the antigen (enzyme) and the anti-idiotypic abzyme, represent a crucial step for the success of this approach. We herein propose to describe a strategy for which we have developed a number of assays, aiming at selecting the proper Ab1, with desired features, likely to elicit an anti-idiotypic catalytic antibody. beta-Lactamase from Bacillus cereus was chosen as the example illustrating our arguments.