Plasma Clusterin Concentrations May Predict Resistance to Intravenous Immunoglobulin in Patients with Kawasaki Disease

Abstract

Kawasaki disease (KD) is an acute febrile vasculitic syndrome of early childhood often complicated by coronary artery lesion that drastically reduces the quality of life. The study aimed to identify a reliable marker for predicting nonresponsiveness to the first course of intravenous immunoglobulin (IVIG) in KD patients. A total of 63 patients with KD were enrolled in the study (IVIG response, 58; IVIG resistance, 5). Plasma samples were collected before and after IVIG infusion for measurement of biomarkers. Patients' clinical characteristics and laboratory data were also analyzed. A receiver operating characteristic curve was generated to identify a cut-off value for predicting IVIG resistance. Among the biomarkers, the difference in plasma clusterin concentrations before and after IVIG infusion (CLUSTER 12) was significantly related to IVIG resistance (P = 0.040; 95% confidence interval (CI): −25.8% to −6.0%). Using a CLUSTER 12 cut-off value of <8.52 mg/L, the odds ratio for IVIG resistance was 11.467 (95% CI: 1.186 to 110.853). Patients with plasma CLUSTER 12 concentrations >8.52 mg/L had a much higher risk of IVIG resistance than those with CLUSTER 12 concentrations <8.52 mg/L. Plasma clusterin concentration shows promise as a candidate biomarker for predicting IVIG resistance in patients with KD.

Prediction for Intravenous Immunoglobulin Resistance by Using Weighted Genetic Risk Score Identified From Genome-Wide Association Study in Kawasaki Disease

“…The biomarkers include patients’ age, illness day, serum markers (including platelet count, erythrocyte sedimentation rate, hemoglobin concentration, C-reactive protein, eosinophil counts, lactate dehydrogenase, plasma level of albumin, alanine aminotransferase, clusterin, and granulocyte colony-stimulating factor), and sonographic gallbladder abnormalities. 42 – 47 In addition, genetic variations were reported to associate with IVIG resistance in KD patients. The genetic markers include FcγR family, inositol 1,4,5-trisphosphate 3-kinase C ( ITPKC ), caspase-3 ( CASP3 ), CD209, CCR2-CCR5, CCL3L1, interleukin 1 beta (IL-1B) , and platelet-activating factor acetylhydrolase .…”

Predictors of intravenous immunoglobulin-resistant Kawasaki disease in children: a meta-analysis of 4442 cases

“…The results of 20 studies were combined in this study comprising 18 Asian studies [4, 6, 9, 10, 13, 17, 19, 20, 22, 24–26, 29, 32, 33, 37, 41, 44] and 2 North American studies [18, 38]. Each subgroup analysis showed the results had statistical significance; however, Baek et al [2] reported that ESR and platelet count could not predict IVIG-resistant Kawasaki disease from their statistical meta-analysis, which is contrary to the results of the present study.…”

Association of HMGB1, S100A12 and IL-17A Expression with Immunoglobulin-Resistant in Kawasaki Disease and the Comparisons Between Different Adjunctive Therapeutic Approaches

“…Kawasaki disease (KD) is an acute febrile illness associated with vasculitis of early childhood often complicated by coronary artery lesion that signi cantly impair the quality of life [28][29][30]. The study aimed to identify some reliable indicators for predicting nonresponsiveness to the rst course of intravenous immunoglobulin (IVIG) in KD patients [3,17].Developing the early judgment of IVIG-resistant in patients with KD is crucial for earlier and more effective initial therapy in patients [2].Although several predictive biomarkers and genes have been described. There have been no reliable criteria and consistent reported for identifying children most at risk of IVIG-resistant and developing CAL.…”