IgA Levels Are Associated with Coronary Artery Lesions in Kawasaki Disease

Background and Objectives@#Kawasaki disease (KD) is an acute systemic vasculitis that affects the coronary arteries. Abnormal immune reactions are thought to contribute to disease pathogenesis. The effect of immunoglobulin (Ig) isotype (IgG, IgA, IgM, and IgE) on inflammatory data and clinical outcomes of patients with KD was examined. @*Methods@#Ig levels in 241 patients with KD were measured during the acute, subacute, convalescent, and normal phases of the disease. @*Results@#Compared with reference Ig values, IgG, IgA, and IgM levels were significantly higher in the subacute phase, while IgE levels were elevated in 73.9% (178/241) of patients with KD in all clinical phases. However, high IgE levels were not associated with clinical outcomes, including intravenous immunoglobulin unresponsiveness and coronary artery lesions (CALs).Significantly more CALs were observed in the high IgA group than in the normal IgA group (44.7% vs. 20.8%, respectively; p<0.01). In addition, IgA levels in the acute phase (p=0.038) were 2.2-fold higher, and those in the subacute phase were 1.7-fold higher (p <0.001), in the CAL group than in the non-CAL group. IgA concentrations increased along with the size of the coronary artery aneurysm (p <0.001). Furthermore, there was a strong correlation between IgA levels and CAL size (r=0.435, p<0.001), with a high odds ratio of 2.58 (p=0.022). @*Conclusions@#High IgA levels in patients with KD are prognostic for the risk of CALs.

IgA Levels Are Associated with Coronary Artery Lesions in Kawasaki Disease

Background and Objectives@#Kawasaki disease (KD) is an acute systemic vasculitis that affects the coronary arteries. Abnormal immune reactions are thought to contribute to disease pathogenesis. The effect of immunoglobulin (Ig) isotype (IgG, IgA, IgM, and IgE) on inflammatory data and clinical outcomes of patients with KD was examined. @*Methods@#Ig levels in 241 patients with KD were measured during the acute, subacute, convalescent, and normal phases of the disease. @*Results@#Compared with reference Ig values, IgG, IgA, and IgM levels were significantly higher in the subacute phase, while IgE levels were elevated in 73.9% (178/241) of patients with KD in all clinical phases. However, high IgE levels were not associated with clinical outcomes, including intravenous immunoglobulin unresponsiveness and coronary artery lesions (CALs).Significantly more CALs were observed in the high IgA group than in the normal IgA group (44.7% vs. 20.8%, respectively; p<0.01). In addition, IgA levels in the acute phase (p=0.038) were 2.2-fold higher, and those in the subacute phase were 1.7-fold higher (p <0.001), in the CAL group than in the non-CAL group. IgA concentrations increased along with the size of the coronary artery aneurysm (p <0.001). Furthermore, there was a strong correlation between IgA levels and CAL size (r=0.435, p<0.001), with a high odds ratio of 2.58 (p=0.022). @*Conclusions@#High IgA levels in patients with KD are prognostic for the risk of CALs.

Identification of rare coding variants associated with Kawasaki disease by whole exome sequencing

Kawasaki disease (KD) is an acute pediatric vasculitis that affects genetically susceptible infants and children. To identify coding variants that influence susceptibility to KD, we conducted whole exome sequencing of 159 patients with KD and 902 controls, and performed a replication study in an independent 586 cases and 732 controls. We identified five rare coding variants in five genes (FCRLA, PTGER4, IL17F, CARD11, and SIGLEC10) associated with KD (odds ratio [OR], 1.18–4.41; p = 0.0027–0.031). We also performed association analysis in 26 KD patients with coronary artery aneurysms (CAAs; diameter > 5 mm) and 124 patients without CAAs (diameter < 3 mm), and identified another five rare coding variants in five genes (FGFR4, IL31RA, FNDC1, MMP8, and FOXN1), which may be associated with CAA (OR, 3.89–37.3; p = 0.0058–0.0261). These results provide insights into new candidate genes and genetic variants potentially involved in the development of KD and CAA.

Clinical Significance of the Bacille Calmette-Guérin Site Reaction in Kawasaki Disease Patients Aged Less than 18 Months

PURPOSE: The purpose of this study was to investigate the clinical significance of Bacille Calmette-Guérin (BCG) site reaction in terms of diagnosis and outcome prediction in young children with Kawasaki disease (KD). METHODS: The incidence of BCG site reaction in the respective age ranges was investigated in 1,058 patients who were admitted at Asan Medical Center between January 2006 and February 2017. The 416 patients under 18 months of age were enrolled as subjects for the analysis of the association between BCG site reaction and other laboratory and clinical findings. The analysis was performed separately in complete and incomplete KD groups. RESULTS: The incidence rate of BCG site reaction was peaked at 6–12 months (83%) and decreased with increasing age after 12 months in 1,058 patients (P < 0.001). The incidence rate was above 70% in KD aged less than 18 months and more frequent than those of cervical lymphadenopathy. The logistic regression analyses showed that the principal clinical findings including conjunctivitis (P=0.781), red lips/oral mucosa (P=0.963), rash (P=0.510), cervical lymphadenopathy (P=0.363), changes in extremities (P=0.283) and the coronary artery aneurysm (P=0.776) were not associated with the BCG site reaction. CONCLUSIONS: The BCG site reaction could be a useful diagnostic tool independent to principal clinical findings in KD developing in children aged < 18 months, who underwent BCG vaccination. Outcome of KD patients was not different between groups with or without the BCG site reaction in both complete KD and incomplete KD.

A comparative study of established z score models for coronary artery diameters in 181 healthy Korean children / 소아과

PURPOSE: The aim of this study was to investigate the statistical properties of four previously developed pediatric coronary artery z score models in healthy Korean children. METHODS: The study subjects were 181 healthy Korean children, whose age ranged from 1 month to 15 years. The diameter of each coronary artery was measured using 2-dimensional echocardiography and converted to the z score in the four models (McCrindle, Olivieri, Dallaire, and Japanese model). Descriptive statistical analyses and 1-sample t tests were performed. RESULTS: All calculated z scores had P values of ≥0.050 using the Kolmogorov-Smirnov test. The one sample t test showed that the mean z scores did not converge to zero except in 1 model, and the mean right coronary artery (RCA) z score was less than zero in all 4 models. The smaller RCA diameter in this study could be associated with the more distal measuring point used to avoid the conal branch. The percentage of subjects with extreme z score values (≥2.0 and ≥2.5) for the left main coronary artery (LMCA) seems to be higher in the Dallaire (4.9% and 3.3%) and Japanese models (7.1% and 3.8%). CONCLUSION: All 4 models showed statistical feasibility of normal distribution. More precise instructions would be needed for the measurement of the RCA. The higher percentage of extreme z scores for the LMCA is compatible with the basic understanding of anatomic variation in the LMCA.

Prediction of unresponsiveness to second intravenous immunoglobulin treatment in patients with Kawasaki disease refractory to initial treatment / 소아과

PURPOSE: This study investigated predictors of unresponsiveness to second-line intravenous immunoglobulin (IVIG) treatment for Kawasaki disease (KD). METHODS: This was a single-center analysis of the medical records of 588 patients with KD who had been admitted to Asan Medical Center between 2006 and 2014. Related clinical and laboratory data were analyzed by univariate and multivariate logistic regression analyses. RESULTS: Eighty (13.6%) of the 588 patients with KD were unresponsive to the initial IVIG treatment and received a second dose. For these 80 patients, univariate analysis of the laboratory results obtained before administering the second-line IVIG treatment showed that white blood cell count, neutrophil percent, hemoglobin level, platelet count, serum protein level, albumin level, potassium level, and C-reactive protein level were significant predictors. The addition of methyl prednisolone to the second-line regimen was not associated with treatment response (odds ratio [OR], 0.871; 95% confidence interval [CI], 0.216–3.512; P=0.846). Multivariate analysis revealed serum protein level to be the only predictor of unresponsiveness to the second-line treatment (OR, 0.160; 95% CI, 0.028–0.911; P=0.039). Receiver operating characteristic curve analysis to determine predictors of unresponsiveness to the second dose of IVIG showed a sensitivity of 100% and specificity of 72% at a serum protein cutoff level of <7.15 g/dL. CONCLUSION: The serum protein level of the patient prior to the second dose of IVIG is a significant predictor of unresponsiveness. The addition of methyl prednisolone to the second-line regimen produces no treatment benefit.

Diagnostic characteristics of supplemental laboratory criteria for incomplete Kawasaki disease in children with complete Kawasaki disease / 소아과

PURPOSE: In 2004, the American Heart Association (AHA) had published an algorithm for the diagnosis of incomplete Kawasaki disease (KD). The aim of the present study was to investigate characteristics of supplemental laboratory criteria in this algorithm. METHODS: We retrospectively examined the medical records of 355 patients with KD who were treated with intravenous immunoglobulin (IVIG) during the acute phase of the disease. Laboratory data were obtained before the initial IVIG administration and up to 10 days after fever onset. In 106 patients, laboratory testing was performed more than twice. RESULTS: The AHA supplemental laboratory criteria were fulfilled in 90 patients (25.4%), and the frequency of laboratory examination (odds ratio [OR], 1.981; 95% confidence interval [CI], 1.391-2.821; P<0.001) was a significant predictor of it. The fulfillment of AHA supplemental laboratory criteria was significantly associated with refractoriness to the initial IVIG administration (OR, 2.388; 95% CI, 1.182-4.826; P=0.013) and dilatation of coronary arteries (OR, 2.776; 95% CI, 1.519-5.074; P=0.001). CONCLUSION: Repeated laboratory testing increased the rate of fulfillment of the AHA supplemental laboratory criteria in children with KD.