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

Kuo, Ho-Chang; Wong, Henry Sung Ching; Chang, Wei Pin; Chen, Ben Kuen; Wu, Mei; Yang, Kuender D.; Hsieh, Kai‐Sheng; Hsu, Yu Wen; Liu, Shih-Feng; Liu, Xiao; Chang, Wei Chiao

doi:10.1161/circgenetics.116.001625

Cited by 32 publications

(24 citation statements)

References 47 publications

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“…The pathological development of KD is a systemic inflammatory process, during which the severity degree of inflammation is reflected in the duration of fever, more severe or clearer diagnostic clinical manifestations, and higherly activated laboratory parameters such as hemoglobin, baseline platelet count, percentage of neutrophils, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), total bilirubin, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum sodium and other inflammatory biomarkers, which once have been reported to differ remarkably between IVIG non-responders and responders before IVIG infusion. But these factors have no clear consensus on predicting IVIG resistance so far and the conflicting data may derived from ethnic and genetic backgrounds (9,10).…”

Section: Introductionmentioning

confidence: 99%

Risk Factors of Intravenous Immunoglobulin Resistance in Children With Kawasaki Disease: A Meta-Analysis of Case-Control Studies

Liu

Wang

2020

Front. Pediatr.

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Previous studies have shown that children with Kawasaki disease (KD) who fail to respond to intravenous immunoglobulin (IVIG) therapy are at higher risk of developing coronary artery lesions (CALs). We aimed to conduct a meta-analysis to uncover the risk factors associated with IVIG resistance in children with KD. PubMed, Embase, and Cochrane Library databases were searched up to 31st October 2019, and 23 case-control studies were finally eligible, enrolling 2,053 patients of IVIG resistance and 16,635 patients of IVIG sensitivity. Potential factors were comprehensively analyzed by using stata15 software with a standard meta-analysis procedure and consequently found that in addition to patients with polymorphous rash or swelling of extremities symptoms had a tendency to be non-responders, IVIG resistance was more likely to occur in patients with severe anemia, hypoalbuminemia, decreased baseline platelet count, and elevated levels of erythrocyte sedimentation rate (ESR), total bilirubin, alanine aminotransferase (ALT) and neutrophils percentage. Particularly, male sex, hyponatraemia, increased aspartate aminotransferase (AST), and C-reactive protein (CRP) were confirmed as the risk factors favor IVIG resistance in Mongoloids from Asia countries, but not in Caucasians from non-Asia regions. In summary, we report several risk factors relevant to IVIG resistance in children with KD, which may provide guidance for the prediction of IVIG resistance. But a proposing of an optimal prediction system with high specificity and sensitivity needs further studies because of confounding factors.

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Section: Introductionmentioning

confidence: 99%

Risk Factors of Intravenous Immunoglobulin Resistance in Children With Kawasaki Disease: A Meta-Analysis of Case-Control Studies

Liu

Wang

2020

Front. Pediatr.

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“…Kuo et al developed a genetic model to predict IVIG resistance in KD. They identified 11 candidate SNPs in ADTRP, KLF6, EX0C2, ZNF438-ZEB1, and MIR548A3-ZPLD1 genes to calculate a weighted genetic risk score (wGRS) in 126 IVIG responders and 24 IVIG non-responders (52). Patients with IVIG resistance had higher wGRS scores than individuals who were IVIG responsive; however, the wide confident intervals (CIs) for the OR suggest that these findings should be replicated in larger cohorts of patients.…”

Section: Related Risk and Referencesmentioning

confidence: 99%

Current State of Precision Medicine in Primary Systemic Vasculitides

et al. 2019

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“…KD is now the most common cause of acquired heart disease in developing countries [2]which can lead to serious coronary artery lesion [3,4]. Timely a single infusion of 2 g/kg intravenous immunoglobulin (IVIG) along with aspirin [5] can declined the incidence of coronary artery lesions (CALs) effectively [1,6].…”

Section: Introductionmentioning

confidence: 99%

Association of HMGB1, S100A12 and IL-17A Expression with IVIG-Resistant Kawasaki Disease and Treatment Options

Liu¹,

Liu²,

Liu³

et al. 2020

Preprint

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Background: Kawasaki disease (KD) is a medium vessel vasculitis of unknown aetiology that predominantly affecting coronary arteries. The damage-associated molecular pattern molecules (DAMPs) such as HMGB1, S100A12 and IL-17A have been reported to predict poor response to IVIG. Here, we explored the the role of HMGB1, S100A12 and IL-17A in the detection of intravenous immunoglobulin (IVIG)-resistant in KD patients, and to investigate the value of different adjunctive therapy.Method: 126 KD patients and as well as age- and sex-matched 16 febrile control subjects were enrolled in our study. The fresh peripheral blood were collected from KD patients and febrile controls, analyzed the demographic or clinical data and various laboratory parameters. We also measured changes in serum levels of IL-17A and mRNA expression levels of HMGB1 and S100A12 were tested in IVIG-resistant KD patients. Further we explored the association between coronary arteries lesions and different treatment options about IVIG retreatment, methylprednisolone and infliximab for IVIG-resistant KD patients. Result: Regarding laboratory parameters, KD individuals were found to have lower levels of lymphocyte(L)%, prealbumin, CD4+, CD8+ and higher levels of WBC, neutrophil (N)%, CRP, ESR, NT-proBNP, ALT, CD4+/CD8+ (P<0.05 or P<0.01). For KD group, the 53 IVIG-resistant patients had significantly higher levels of S100A12, HMGB1, serum IL-17A, N%, CRP, NT-proBNP, TBIL, ALT, AST and lower levels of L%, PLT (P<0.05 or P<0.01) in comparison to the IVIG-responsive patients. For patients with IVIG-resistant, IVIG retreatment, methylprednisolone or infliximab were used. Methylprednisolone showed better in improving clinical symptoms and CRP than the IVIG retreatment and infliximab (P> 0.05).Conclusion: IVIG-resistant was associated with overreaction of inflammation.The levels of HMGB1,S100A12 and IL-17A suggested to be reliable predictors for IVIG-resistant in KD. In addition, the adjunctive therapy of methylprednisolone and infliximab showed more effective in relieving clinical symptoms than IVIG retreatment.

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

Abstract: Supplemental Digital Content is available in the text.

Cited by 32 publications

References 47 publications

Risk Factors of Intravenous Immunoglobulin Resistance in Children With Kawasaki Disease: A Meta-Analysis of Case-Control Studies

Risk Factors of Intravenous Immunoglobulin Resistance in Children With Kawasaki Disease: A Meta-Analysis of Case-Control Studies

Current State of Precision Medicine in Primary Systemic Vasculitides

Association of HMGB1, S100A12 and IL-17A Expression with IVIG-Resistant Kawasaki Disease and Treatment Options

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