Kawasaki Disease: Laboratory Findings and an Immunopathogenesis on the Premise of a ""Protein Homeostasis System

Lee, Kyung-Yil; Rhim, Jung-Woo; Kang, Jin-Han

Returning to the immunopathogenesis of KD, it is postulated that systemic inflammation of KD is caused by pathogenic proteins which are associated with an immune reaction of an unknown initial infection. In this infection, a majority of the patients may be asymptomatic. The toxic substances produced during the immune reaction against the initial infection may be removed in a majority of the patients, but some patients who have a genetic defect for this feedback process may lead to foci for which the pathogenic proteins are produced and released into systemic circulation. Although the foci producing pathogenic proteins responsible for KD or ARF are unknown, the secondary lymphoid organs around the initial infection sites (tonsils, lymph nodes or Payer's patches) are primary candidates (Fig. 3A) . The pathogenic Superantigens are virulent polypeptides (proteins) that are produced by a variety of infectious organisms including gram positive streptococci and staphylococci. Superantigens can induce activation of many T-cell clones which have specific Vβ chains. However, in any human disease including KD, clinical implications of polyclonal activation of T cells have not been clearly explained. 95 T cells together with other immune cells appear in nearly all pathologic lesions in early stages, before specific T-cells and specific antibodies appear, of infectious diseases, rheumatic disorders including KD and ARF, malignancies as tumor infiltration lymphocytes, tissue rejection, and in the repair processes of tissue injury (keloids). For example, in Mantoux skin tests for diagnosis of tuberculosis, skin tissue injury (positive result) is induced by proteins (purified protein derivatives) and corresponding immune cells, mainly T cells, which were previously sensitized to the proteins from tuberculosis bacilli or Mycobacterium bovis Bacillus Calmette-Guérin (BCG). Positive skin reactions can be abolished in states of depressed T cell function or an exhausted number of T cells in cases of corticosteroid treatment, systemic viral infections such as measles, and severe tuberculosis infections. 30 Furthermore, a clean skin injuries such as scar revision in plastic surgery, in which there are no foreign proteins or pathogens, on occasion result in hypertrophic scars or keloids in genetically susceptible patients. The substances (proteins) from injured skin cells and Immune cells start to control these substances, and clinical symptoms and signs begin to appear. The pathogenic proteins bind to receptors of endothelial cells of coronary arteries, and this process induces cell injury and /or other protein production from endothelial cells (B). Immune cells recruit to the lesions to control the action of the proteins including pathogenic proteins. Initially, non-specific T cells and nonspecific antibodies are involved in this reaction, while hyperactivated immune cells produce various inflammatory cytokines and counterinflammatory cytokines, leading to a cytokine imbalance associated with further endothelial cell injury (C). After emergence of specific T cell clones and specific antibodies for pathogenic proteins, tissue injury ceases and a repair reaction begins with the immune cells (D). KD, Kawasaki disease.