Immune Responses in Kawasaki Disease

Kawasaki disease (KD) is a febrile vasculitis associated with mucocutaneous lesions, lymphadenopathy and cardiovascular events. Typical KD mostly occurs in children less than 5 years of age but atypical KD complicated with macrophage activation syndrome (MAS) or KD shock syndrome (KDSS) occurs in relatively older children, even adults. The etiology of KD remains unclear; however, the immune response is known to mediate by an autoinflammatory innate immune response associated with an imbalance of adaptive immunity showing augmented T helper 17 (Th17)/Th1 responses with higher IL-6, IL-10, IP-10, and IL-17 levels and reduced Th2/Treg responses with lower IL-4, IL-5, FoxP3, and TGFβ expression. This acute autoinflammatory vasculitis may be induced by an exogenous antigen derived from pathogen-associated molecular pattern (PAMP) or an endogenous antigen derived from damage-associated molecular pattern (DAMP). The altered immunity would manifest typical or atypical KD under genetic and environmental backgrounds. Some patients of KD (3-5%) are complicated with KDSS associated with over-production of nitric oxide, coagulopathy and shock symptom, and few patients (1-2%) are complicated with MAS, showing hemophagocytosis, thrombocytopenia, and hyperferritinemia. KD patients with these variant complications usually manifest intravenous immunoglobulin (IVIG) resistance and require additional anti-inflammatory medication. The immune reaction of KD reveals a kinetic progression for early administration of IVIG within 4 days of the illness did not provide a better outcome, and early administration of corticosteroids alone exacerbated the prognosis, but a combination of corticosteroids with IVIG provided the best treatment response. Further studies are proposed to identify the immunopathogenesis of IVIG-resistance, MAS and KDSS, to protect hosts from antigen exposure, and genetic susceptibility, and to combat MAS and/or KDSS by blockade of mechanistic biomarkers, anti-signal transduction, manipulations of host milieu, hit the brakes for immunosuppression and anti-hemophagocytosis.