Kawasaki syndrome: role of superantigens revisited

Abstract

Kawasaki Syndrome (KS) is an acute vasculitis in children complicated by the development of heart disease. Despite its description over 50 years ago, the etiology of coronary artery disease in KS is unknown. High dose intravenous immunoglobulin is the most effective approach to reduce cardiovascular complications. It remains unclear why patients with KS develop coronary artery aneurysms. A subset of patients are resistant to immunoglobulin therapy. Given the heterogeneity of clinical features, variability of history, and therapeutic response, KS may be a cluster of phenotypes triggered by multiple infectious agents and influenced by various environmental, genetic, and immunologic responses. The cause of KS is unknown, and a diagnostic test remains lacking. A better understanding of mechanisms leading to acute KS would contribute to a more precision medicine approach for this complex disease. In the current viewpoint, we make the case for microbial superantigens as important causes of KS.

Impact of the COVID-19 pandemic on the frequency of the pediatric rheumatic diseases

“…Several microbes are capable of producing superantigens which cause excessive activation of the immune system. Superantigens have been implicated in the pathogenesis of Kawasaki disease [ 33 , 34 ]. The prevalence of classic KD decreased during the pandemic period probably due to protective measures and reduced transmission.…”

Superantigenic TCR Vbeta 21.3 signature in Multisystem Inflammatory Syndrome in Children

“…TSS is a severe toxic shock secondary to the superantigen TSST-1 that stimulates human T cells expressing TCR Vβ2(35). A superantigenic T cell response has been already suspected in KD but the multiple infectious agents associated with this disease hampered the exploration of this phenomenon(14). Yet, many KD features suggest this disease is indeed caused by an infectious agent(36).…”

“…Considering the similarities between MIS-C, KD and TSS, it has been hypothesized that SARS-CoV2 may act as a superantigen and induce a hyperinflammatory state in MIS-C(14, 15). Superantigens are molecular structures enabling polyclonal T cell response through binding external region of T cell receptor and MHC class II molecules(16).…”

“…For example, TSS is secondary to the effect of Staphylococcal TSS Toxin-1 (TSST-1) and leads to Vβ2+ T cell expansion(17). In KD, previous reports mentioned the expansion of different Vβ including Vβ2 in response to putative TSST1 but this point is controversial and there could be other causes and triggers of KD(14).…”

Multisystem Inflammatory Syndrome in Children (MIS-C), a Post-viral Myocarditis and Systemic Vasculitis—A Critical Review of Its Pathogenesis and Treatment

“…Superantigens are potent inducers of IL-1 and can induce antigen-independent polyclonal activation of T and B cells as well as activate complement by the alternative pathway (95,96). The role of superantigens has been of great interest in KD (113). The supporting evidence includes findings in the preclinical models (114) using Lactobacillus casei, S. aureus derived TSS toxin (115), or FK565 (116).…”