Yonsei Med J.  2012 Mar;53(2):262-275. 10.3349/ymj.2012.53.2.262.

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

• Lee KY
• Rhim JW
• Kang JH

• KMID: 1120191
• DOI: http://doi.org/10.3349/ymj.2012.53.2.262

Abstract

Kawasaki disease (KD) is a self-limited systemic inflammatory illness, and coronary artery lesions (CALs) are a major complication determining the prognosis of the disease. Epidemiologic studies in Asian children suggest that the etiologic agent(s) of KD may be associated with environmental changes. Laboratory findings are useful for the diagnosis of incomplete KD, and they can guide the next-step in treatment of initial intravenous immunoglobulin non-responders. CALs seem to develop in the early stages of the disease before a peak in inflammation. Therefore early treatment, before the peak in inflammation, is mandatory to reduce the risk of CAL progression and severity of CALs. The immunopathogenesis of KD is more likely that of acute rheumatic fever than scarlet fever. A hypothetical pathogenesis of KD is proposed under the premise of a "protein homeostasis system"; where innate and adaptive immune cells control pathogenic proteins that are toxic to host cells at a molecular level. After an infection of unknown KD pathogen(s), the pathogenic proteins produced from an unknown focus, spread and bind to endothelial cells of coronary arteries as main target cells. To control the action of pathogenic proteins and/or substances from the injured cells, immune cells are activated. Initially, non-specific T cells and non-specific antibodies are involved in this reaction, while hyperactivated immune cells produce various cytokines, leading to a cytokine imbalance associated with further endothelial cell injury. After the emergence of specific T cells and specific antibodies against the pathogenic proteins, tissue injury ceases and a repair reaction begins with the immune cells.

Keyword

Kawasaki disease; coronary artery lesions; laboratory parameters; intravenous immunoglobulin; non-responders; pathogenesis; treatment

MeSH Terms

Animals
Coronary Artery Disease/drug therapy/etiology/metabolism
Humans
Immunoglobulins, Intravenous/therapeutic use
Mucocutaneous Lymph Node Syndrome/complications/*diagnosis/drug therapy/metabolism

Figure

• 

  Fig. 1 Inflammatory intensities of KD patients during febrile periods. a, b and c: Inflammatory intensities of the mildly affected patients (a), moderately affected patients (the average of the patients) (b), and the severely affected patients (c). d: An imaginary threshold line of coronary artery lesions. The severely affected patients reach the threshold line earlier, and before the peak in inflammation. KD, Kawasaki disease.

• 

  Fig. 2 Suspected patterns in the change of laboratory parameters during febrile period. a: bell shaped pattern; CRP, WBC, neutrophil and CPK, b: U shaped pattern; albumin and HDL-cholesterol, c: little changes; ESR and LDH, d: Steadily decrease; AST, ALT, e: steadily increase: total cholesterol, f: increase after the peak; platelet. CRP, C-reactive protein; WBC, white blood cells; CPK, creatine phosphokinase; HDL, high density lipoprotein; ESR, erythrocyte sedimentation rate; LDH, lactic dehydrogenase; ALT, alanine aminotransferase; AST, aspartate aminotransferase.

• 

  Fig. 3 A hypothetical pathogenesis of KD. After an infection by an unknown KD pathogen(s), substances including pathogenic proteins are produced in a focus (potentially secondary immune organs) (A). The substances spread and reach various tissues via systemic circulation. 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 non-specific antibodies are involved in this reaction, while hyperactivated immune cells produce various inflammatory cytokines and counter-inflammatory 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.

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