Sorting nexin 24 genetic variation associates with coronary artery aneurysm severity in Kawasaki disease patients

Lin, Ying; Chang, Jen‐Ping; Liu, Xiang; Lin, Ting Hsu; Huang, Shao Mei; Liao, Chien-Chang; Lin, Cheng Wen; Chien, Wen Kuei; Chen, Jin Hua; Wu, Jer Yuarn; Chen, Chien Hsiun; Chang, Li; Tsang, Hsinyi; Jeang, Kuan Teh; Chen, Chia Yen; Tsai, Fuu Jen

doi:10.1186/2045-3701-3-44

Cited by 15 publications

(12 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During the acute phase of KD, the immune system is activated resulting in an increase in pro-inflammatory cytokines in the circulation. That these inflammatory cytokines may cause local and systemic damage has been supported by clinical findings and in the animal model [27–30]. In the Lactobacillus casei cell-wall extract (LCWE) induced mouse model of KD, IL-1 signaling pathways were involved in vasculitis, coronary arteritis and abdominal aortic aneurysm [31, 32].…”

Section: Discussionmentioning

confidence: 99%

Kawasaki disease shock syndrome: clinical characteristics and possible use of IL-6, IL-10 and IFN-γ as biomarkers for early recognition

et al. 2019

View full text Add to dashboard Cite

BackgroundAs an acute febrile and inflammatory disease, Kawasaki disease (KD) could develop Kawasaki disease shock syndrome (KDSS) sometimes. However its pathogenesis was still not well known. This study was to learn more about the clinical features and evaluate the role of cytokines in the pathogenesis of KDSS.MethodsWe collected clinical and laboratory data retrospectively for all patients with KDSS(KDSS, n = 27)who were hospitalized at our hospital from Jan 2014 to Oct 2017. For patient with KDSS, we randomly identified 43 patients with KD as control subjects (KD, n = 43). Clinical features, laboratory evaluations were collected. Cytokines IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in serum were assayed using flow cytometric bead array.ResultsThe patients with KDSS were older age (43.41 ± 31.42 vs 28.81 ± 21.51 months, P < 0.05), longer duration of fever (10.63 ± 5.12 vs 6.98 ± 2.45 days, P < 0.05), higher WBC count, neutrophils, CRP, ESR, PCT and D-dimer, and lower hemoglobin and albumin, more severe hyponatremia and hypokalemia, more refractory to IVIG therapy, more coronary artery abnormalities (CAAs), aseptic meningitis, and longer duration of hospitalization than patients with KD (all P < 0.05). The levels of serum IL-6 [184.1 (27.7–2577.3) vs 54.1 (4–425) pg/ml], IL-10 [42.6 (5–236.7) vs 9.4 (3–94) pg/ml], TNF-α [2.6 (1.0–23.4) vs 2.1 (1–6) pg/ml] and IFN-γ [18.3 (4.5–94.4) vs 6.7 (2–56) pg/ml] in KDSS patients were significant higher than KD patients (all P < 0.05). ROC curves showed that 66.7 pg/ml of IL-6, 20.85 pg/ml of IL-10 and 8.35 pg/ml of IFN-γ had sensitivity and specificity for identifying KDSS as 85.2 and 62.8%; 66.7 and 83.7%; 74.1 and 74.4% respectively. No fatality was recorded in this series.ConclusionsKDSS were characteristic as more cytokine production and prone to developing IVIG non-responsiveness and CAAs. KD patients with IL-6 above 66.7 pg/ml, IL-10 above 20.85 pg/ml, and IFN-γ above 8.35 pg/ml suggested higher risk for KDSS.

show abstract

Section: Discussionmentioning

confidence: 99%

Kawasaki disease shock syndrome: clinical characteristics and possible use of IL-6, IL-10 and IFN-γ as biomarkers for early recognition

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Written informed consent was obtained from the participants or their parent or legal guardian. Two hundred and sixty-two unrelated patients fulfilling the KD diagnostic criteria were identified and enrolled from the Children’s Hospital of China Medical University in Taichung, Taiwan 25 42 52 53 54 . There were 76 patients with KD with CAA complications and 186 patients with KD without CAA complications, with an average age at onset of 1.86 ± 1.78 and 1.70 ± 1.51 years old, respectively ( Table S1 ).…”

Section: Methodsmentioning

confidence: 99%

Genetic variants in PLCB4/PLCB1 as susceptibility loci for coronary artery aneurysm formation in Kawasaki disease in Han Chinese in Taiwan

Lin

Chang

Liu

et al. 2015

Sci Rep

Self Cite

View full text Add to dashboard Cite

Kawasaki disease (KD) is an acute, inflammatory, and self-limited vasculitis affecting infants and young children. Coronary artery aneurysm (CAA) formation is the major complication of KD and the leading cause of acquired cardiovascular disease among children. To identify susceptible loci that might predispose patients with KD to CAA formation, a genome-wide association screen was performed in a Taiwanese KD cohort. Patients with both KD and CAA had longer fever duration and delayed intravenous immunoglobulin treatment time. After adjusting for these factors, 100 susceptibility loci were identified. Four genes were identified from a single cluster of 35 using the Ingenuity Pathway Analysis (IPA) Knowledge Base. Silencing KCNQ5, PLCB1, PLCB4, and PLCL1 inhibited the effect of lipopolysaccharide-induced endothelial cell inflammation with varying degrees of proinflammatory cytokine expression. PLCB1 showed the most significant inhibition. Endothelial cell inflammation was also inhibited by using a phospholipase C (PLC) inhibitor. The single nucleotide polymorphism rs6140791 was identified between PLCB4 and PLCB1. Plasma PLC levels were higher in patients with KD and CC+CG rs6140791genotypes, and these genotypes were more prevalent in patients with KD who also had CAA. Our results suggest that polymorphism of the PLCB4/B1 genes might be involved in the CAA pathogenesis of KD.

show abstract

“…Furthermore, a wide variety of underlying etiologies, other than atherosclerosis, were found later to be associated with CAE. Nonetheless, genetic predisposition and environmental factors may play a role as well in this complex phenomenon [6,25,26].…”

Section: Pathogenesismentioning

confidence: 99%

Coronary Artery Ectasia in Atherosclerotic Coronary Artery Disease, Inflammatory Disorders, and Sickle Cell Disease

Dahhan

2015

Cardiovascular Therapeutics

View full text Add to dashboard Cite

SUMMARYCoronary artery ectasia (CAE) or aneurysm is usually defined as dilation ≥1.5-fold the normal vessel diameter. It has an incidence of 1.4-5.3% and is associated with a wide variety of etiologies-mainly congenital, atherosclerotic, and inflammatory ones. CAE is very common in sickle cell disease, and possibly sickle cell trait, with an incidence of 17.7%. It is likely related to the inflammatory process associated with hemoglobin S. Prognosis depends mainly on the underlying etiology. Atherosclerotic CAE does not carry additional risks compared to atherosclerotic coronary artery disease (ACAD) without ectasia. However, isolated CAE in the absence of ACAD carries an increased risk of myocardial infarction (MI) due to vasospasm, slower coronary blood flow, and thrombosis, typically within the dilated segments. Due to lack of studies and guidelines, management recommendations are based on personal experiences. Therapy should be tailored to each individual case after assessment of severity, history of complications, underlying etiology, and comorbidities. Treatment of underlying condition and avoidance of exacerbating factors are essential. Medical therapy in general may include antiplatelets, b-blockers, angiotensin-converting enzyme inhibitors statins, and dihydropyridine calcium channel blockers. In severe CAE or history of MI, the addition of anticoagulation therapy after assessing bleeding risk may be warranted. In acute MI, the large thrombus burden in the dilated segment makes the percutaneous approach very challenging. Aspiration attempts can result in distal thromboembolization. Survival is better in bypass grafting than with medical therapy. Nonetheless, bypass grafting does not improve survival in atherosclerotic CAE. Depending on the physical characteristics of aneurysm, different surgical approaches can be sought; however, the ideal one is unclear.

show abstract

Sorting nexin 24 genetic variation associates with coronary artery aneurysm severity in Kawasaki disease patients

Cited by 15 publications

References 41 publications

Kawasaki disease shock syndrome: clinical characteristics and possible use of IL-6, IL-10 and IFN-γ as biomarkers for early recognition

Kawasaki disease shock syndrome: clinical characteristics and possible use of IL-6, IL-10 and IFN-γ as biomarkers for early recognition

Genetic variants in PLCB4/PLCB1 as susceptibility loci for coronary artery aneurysm formation in Kawasaki disease in Han Chinese in Taiwan

Coronary Artery Ectasia in Atherosclerotic Coronary Artery Disease, Inflammatory Disorders, and Sickle Cell Disease

Contact Info

Product

Resources

About