Pharmacodynamics And Active Mechanism Of Antural Anti-keratin Autoantibodies

Natural autoantibodies (NAA) refer to antibodies that are present in the serum of healthy individuals and can bind to one or more self-antigens in the absence of deliberate immunization. NAA are one of important parts of physiological autoimmunity, i.e. normal autoimmunity. In human and animal bodies generally exist various NAA recognizing autoantigens that include a great number of components in the body. NAA are encoded by germline genes and belong to 1gM, IgG, IgA isotypes. Comprising the network of idiotype and antiidiotype, NAA are one of important parts of immune systme. NAA play an important role in immune homeostasis, non-specific defense, anti-inflammatory activity, tumor surveillance, immune regulation, catalytic activity, transportation of small active molecule, and so on. -6- As a member of NAA, anti-keratin autoantibodies (AK auto Ab) are extensively present in the serum of human and most of the animals, exerting important function in many physiological and pathological processes. Since its first discovery by Krogh, scientists have made thorough research on AK auto Ab抯 biological property, immunological function, and physiological and pathological significance. In vitro experiments indicated that purified AK auto Ab inhibit the proliferation of keratinocyte and induce the apoptosis of keratinocyte, and that treatment of keratinocyte cultured in vitro with AK auto Ab of different concentrations can inhibit the IL-1f3-caused production of JL-6 and IL-8. Animal experiments showed that when animals with different titers of serum AK auto Ab were afflicted with cold injury, scald and contact dermatitis, there were significant difference in inflammatory reaction, tissue injury and repair process of the animals. When serum AK auto Ab titer was normal, AK auto Abs were locally deposited on the regions of injured skin under above pathological conditions, playing a positive role in the protection and repair of tissue; on the contrary, when serum AK auto Ab titer was low, the tissue injury was serious and the repair was slow under pathological conditions. This indicated that AK auto Ab can actively participate in the pathophysiological processes of some diseases. Wei Li established rabbit models of irritative contact dermatitis. It was found that human AK auto Abs take a positive part in the -7- inflammatory reaction and tissue repair of rabbit model of irritative contact dermatitis. In order to observe possible side effects after long-term application of homologuous AK auto Ab to rabbits and study the possibility of development of AK auto Ab as a therapeutic agent, we purified AK auto Ab from pooled rabbit serum and administered purified antibodies to rabbit by injection. Then, we detected the production of anti-idiotypic antibody against AK auto Ab and observed the influence of AK auto Ab on the body抯 vital organs. We also studied the mechanism of homologuous AK auto Ab抯 influence on contact dermatitis, using rabbit model of contact dermatitis. In the present research, AK auto Ab were purified from pooled rabbit serum using keratin affinity column prepared with activated Sepharose 4B and epidermal keratins extracted from rabbit skin. In expertimental group, rabbits were injected with purified AK...