Adaptive control: a strategy to treat autoimmunity.
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.
Sulzer
B
B
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
van Hemmen
J L
JL
D000888:Antibodies, Anti-Idiotypic / Q000627:therapeutic use*; D000941:Antigens / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood*; D001327:Autoimmune Diseases / Q000628:therapy*; D001402:B-Lymphocytes / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007267:Injections; D018448:Models, Immunological; D013997:Time Factors
D000888:Antibodies, Anti-Idiotypic; D000941:Antigens; D001323:Autoantibodies