Superantigens as Contributors to the Etiology of Kawasaki Disease Shock Syndrome.

Background: Before the COVID-19 pandemic, the higher prevalence of gastrointestinal symptoms, severe inflammatory response, and cardiac failure in patients with Kawasaki Disease Shock Syndrome (KDSS) lets us hypothesize that KDSS is triggered by superantigens produced by bacteria that colonize the gastrointestinal tract and activate TCRVβ2+ and TCRVβ8+ cells, leading to a massive proinflammatory stage and cardiovascular instability. Methods: This is a case-control study in patients with KDSS (cases, 8 patients) or with Kawasaki disease (KD; controls, 71 patients), in the acute phase before intravenous immunoglobulin (IVIG) treatment, from the National Institute of Pediatrics, Mexico City, from 2016 to 2019. Clinical and laboratory data were obtained with quantification of TCRVβ2+ and TCRVβ8+ T cells by flow cytometry. Superantigen-associated gene-positive bacterial isolates from stool cultures were obtained by final point-PCR assay. Statistical analysis was done with one-way ANOVA and Welch's post hoc test, Chi-square test and odds ratio (OR). Statistical significance was defined as p < 0.05. Results: The peripheral proportion of CD4+TCRVβ2+ T cells was lower in the KDSS group than in the KD group, whereas the CD25-positive T-cell subsets showed no statistically significant differences between groups. Significant associations between staphylococcus enterotoxin A (SEA)/KDSS [OR = 23.3, CI95% = 1.8-296.2, p = 0.014] and superantigen/coronary aneurysms (p < 0.001) were found. Conclusions: These results suggest that SEA produced by bacteria that colonize the gastrointestinal tract and cross the intestinal barrier may activate CD3+/CD4+/TCRVβ2+ T cells, as a trigger of shock in a group of patients with KD. Also, each subtype of KD could have different etiologies explaining the inconsistencies in the detection of superantigens in patients with KD.