Open AccessImmunologic aspects of Kawasaki disease: Implications for pathogenesis and therapy
Author(s) -
Leung Donald Y. M.
Publication year - 1991
Publication title -
clinical cardiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.263
H-Index - 72
eISSN - 1932-8737
pISSN - 0160-9289
DOI - 10.1002/clc.4960140603
Subject(s) - medicine , immunology , kawasaki disease , pathogenesis , antigen , vasculitis , rash , endothelium , cytokine , pathology , disease , artery
Summary : Kawasaki disease (KD) is an acute vasculitis primarily affecting infants and young children. It is characterized by prolonged fever, bilateral nonexudative conjunctivitis, induration and erythema of the hands and feet, inflammation of the lips and oropharynx, polymorphous skin rash, and cervical lymphadenopathy. Left untreated, up to 30% of cases may be associated with the development of coronary artery abnormalities. Reports that high‐dose intravenous immune globulin (IVIG) significantly reduces the occurrence of coronary artery aneurysms in patients with KD suggest that immunologic processes play a significant role in the pathogenesis of this syndrome. An immunologic basis for KD is further supported by the observation of a T‐cell imbalance during the acute phase of the disease and the increased production of cytokines that occurs during the acute phase but not during convalescence. Histologic evaluation of vascular lesions reveals adhesion of leukocytes to the endothelial wall, infiltration of neutrophils and mononuclear cells, and the expression of class II major histocompatibility complex antigens on coronary artery endothelium. It also has been demonstrated that during the acute phase, there is an appearance of circulating antibodies cytotoxic to endothelial cells that have been activated with interleukin‐1, tumor necrosis factor‐α, or interferon‐γ but not to unstimulated cells. These observations have led us to postulate that endothelial cell injury requires (1) the induction of new endothelial cell antigens in response to increased cytokine production and (2) the generation of antibodies directed against these antigens. A number of multicenter trials have demonstrated that high‐dose IVIG in combination with aspirin effectively reduces the prevalence of coronary artery abnormalities. The mechanism by which IVIG reduces vasculitis is not precisely known. However, there is evidence that the clinical benefit of IVIG in KD is derived from immunoregulatory effects that work to reduce cytokine secretion and thus reverse endothelial activation.