Association of Toll-like receptor 2-positive monocytes with coronary artery lesions and treatment nonresponse in Kawasaki disease

Abstract

PurposeActivation of Toll-like receptor 2 (TLR2) present on circulating monocytes in patients with Kawasaki disease (KD) can lead to the production of proinflammatory cytokines and interleukin-10 (IL-10). We aimed to determine the association of the frequency of circulating TLR2+/CD14+ monocytes (FTLR2%) with the outcomes of KD, as well as to compare FTLR2% to the usefulness of sIL-10.MethodsThe FTLR2% in patients with KD was measured by flow cytometry. Serum levels of IL-10 (sIL-10) were determined in 31 patients with KD before the initial treatment with intravenous immunoglobulin (IVIG) and in 21 febrile controls by using enzyme-linked immunosorbent assay. Patients were classified as having coronary artery lesions (CALs) based on the maximal internal diameters of the proximal right coronary artery and proximal left anterior descending coronary artery one month after the initial diagnosis.ResultsWe found that FTLR2% greater than 92.62% predicted CALs with 80% sensitivity and 68.4% specificity, whereas FTLR2% more than 94.61% predicted IVIG resistance with 66.7% sensitivity and 71.4% specificity. Moreover, sIL-10 more than 15.52 pg/mL predicted CALs and IVIG resistance with 40% and 66.7% sensitivity, respectively, and 73.7% and 76.2% specificity, respectively.ConclusionWe showed that measuring FTLR2% before the initial treatment could be useful in predicting CAL development with better sensitivity than sIL-10 and with results comparable to sIL-10 results for the prediction of IVIG resistance in patients with KD. However, further studies are necessary to validate FTLR2% as a marker of prognosis and severity of KD.

Comparable bidirectional neutrophil immune dysregulation between Kawasaki disease and severe COVID-19

“…Mounting evidence has indicated that the regulation of toll-like receptors participates in the pathogenesis of KD ( 30 ) by stimulating neutrophil migration ( 31 – 33 ). More importantly, both neutrophil migration and transformation were associated with shock syndrome, a refractory response to IVIG and coronary artery lesions (CAL) in KD ( 34 – 36 ). Neutrophil activation has been reported to be enhanced with a marked increase in ROS, which contributes to the excessive formation of neutrophil extracellular traps (NETs), which has been suggested as being involved in the pathogenesis of KD ( 31 , 37 – 39 ), as well as the severity of acute respiratory syndrome caused by SARS-CoV-2 and severe COVID-19 patients who have cardiovascular injuries ( 40 – 42 ).…”

Epigenetic Regulation of Macrophage Marker Expression Profiles in Kawasaki Disease

“…Previous research has found that toll-like receptors, particularly toll-like receptor 2 (TLR2) is associated with the development of KD. In human patients with KD, increased expression of TLR2 positive CD14 monocytes occurs in the acute phase of KD (22), and is down regulated after IVIG therapy (30), and can successfully predict risk of coronary artery lesions and IVIG resistance (31). In mouse models of KD, mice which were TLR2 or MyD88 deficient failed to develop KD after induction by Lactobacillus casei cell-wall extract (LCCWE), suggesting that TLR2 signaling through the MyD88 pathway is crucial for the development of KD (32).…”

Combination of S100A12/TLR2 signaling molecules and clinical indicators in a new predictive model for IVIG-resistant Kawasaki disease

“…The typical treatment for this disease is a single intravenous injection of immunoglobulin (IVIG) at a dose of 2 g/kg in combination with oral aspirin, which reduces the chances of coronary artery damage to 5% 2 . Moreover, the incidence of coronary artery damage is high in patients with IVIG resistance 4 , with approximately 10–20% of patients experiencing coronary artery damage 5 . Thus, this condition requires clinician attention and effective treatment to resolve the inflammatory process and improve patient prognosis.…”