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

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

Since KD was first seen in the early 1960's in Japan, 1 KD has been recognized worldwide. Epidemiological studies in Far East Asian countries including Japan, Korea, Taiwan and China have revealed that KD is a new disease with similar epidemiologic patterns in these countries; after the initial appearance of KD, the incidence of KD showed a gradual increase for a decade up to a nationwide occurrence (becoming an endemic disease), and then KD occurred everywhere with relatively constant but slowly growing rates. [19] [20] [21] The appearance and subsequent incidence of KD may be associated with the time of industrialization and westernization of these countries. 13 Therefore, it could be postulated that in the past, KD (infantile polyarteritis nodosa) might have appeared in Western countries around the beginning of the 20th century. Throughout the past decade, KD has appeared in rapidly modernizing countries, including India, where KD is more prevalent in modernized cities of economically higher income. 22 Environmental factors such as improved public hygiene or westernized lifestyles may be associated with the emergence and establishment of KD. In South Korea, although yearly incidence rates show no remarkable spatial (geographical) and temporal (seasonal) differences, 19 recently, clinical features of KD seem to be changing to milder phenotypes with greater numbers of incomplete KD cases. 23 In children of other ethnicities, it was also reported that the clinical features of a disease in an outbreak seem to differ from previous outbreaks. 24, 25 These findings suggest that the etiology of KD may not be due to a single agent and raise aseptic meningitis, anterior uveitis, gall bladder hydrops, urethritis and lung involvement can be seen. 2 Some more severely affected patients show cardiac complications, particularly coronary artery lesions (CALs) such as aneurysms and ectasias, which develop in approximately one quarter of untreated children and 5-10% of intravenous immunoglobulin (IVIG) treated children. 3, 4 These diverse systemic inflammations (mainly vasculitis) may be caused by inflammatory mediators with circulating immune cells (neutrophils, lymphocytes, natural killer cells and monocytes), and there may be various immune cell infiltrations in all affected pathologic lesions from affected lymph nodes to skin rashes. Particularly, a larger number of T cells (more CD8 cells than CD4 cells), large mononuclear cells, macrophages and plasma cells, with a smaller number of neutrophils, are observed in various organ tissues of fatal cases of acute KD. [5] [6] [7] [8] In addition, peripheral blood analysis of acute KD patients showed T lymphocytopenia with depressed CD8 T cells, increased activated CD4 T cells and depressed CD4+CD25+ regulatory T cells. [9] [10] [11] These findings suggest that the majority of circulating T cells move to the pathologic lesions of various tissues in acute KD. Therefore, circulating immune cells, especially T cells, control the inflammation of the majority of the affected regions of KD patients without sequelae, but they also may be involved in the progression of the disease, such as in the case of CALs. Epidemiological and clinical data suggest that KD is an immunological reaction to infectious triggers occurring in genetically susceptible children. Although studies have provided hypothetical explanations for the pathogenesis of KD, the etiologic agents, the immunopathogenesis of the vasculitis, and the m