Single-cell multi-omics sequencing reveals the immunological disturbance underlying Kawasaki disease.

Macrophage activation syndrome (MAS) is a rare, life-threatening complication of Kawasaki disease (KD). Early recognition and treatment of MAS are very important, but sometimes it is difficult to distinguish MAS from a severe form of KD. A PubMed search was performed in Clinical Queries using the key terms "macrophage activation syndrome or secondary hemophagocytic lymphohistiocytosis (HLH)" and "Kawasaki disease". KD patients with MAS show high intravenous immunoglobulin (IVIG) resistance and coronary complications. Mortality is also as high as MAS in other diseases. Persistent fever greater than 10days is highly associated with development of MAS in KD. Splenomegaly is observed in more than two-thirds of KD patients with MAS. Thrombocytopenia is often the earliest laboratory finding of MAS. Hyperferritinemia is highly specific and sensitive for detecting MAS in KD; so, ferritin levels should be checked if there are unexplained clinical exacerbations in KD patients. Given the under-recognition of MAS in KD, it is prudent to consider resistant KD as occult/subclinical MAS. Many KD patients with MAS have good outcomes on immune modulators. However, if KD patients fulfill the HLH-2004 diagnostic criteria, they may undergo longer and more intensive treatment than needed. The possible existence of MAS should be taken into account when a KD patient shows persistent fever, splenomegaly, thrombocytopenia, hyperferritinemia, or IVIG resistance. The under-diagnosis of MAS in patients with KD is an important issue to be addressed. Therapeutically, however, there is a possibility of over-treatment of MAS in patients with KD.

Background Intravenous immunoglobulin (IVIG) resistance is of prime importance in Kawasaki disease (KD). In this study, we examined the value and mechanism of serum amyloid A (SAA) level in predicting IVIG resistance in patients with KD. Methods SAA levels were measured in 497 consecutive patients with KD before IVIG therapy in the training set. The patients were divided into two groups (IVIG-responsive and IVIG-resistant) according to the American Heart Association (AHA) definition of IVIG resistance. Demographic, echocardiographic, and laboratory data were also retrospectively analyzed and tabulated to predict IVIG resistance. The predictive value of SAA was validated on test sets of prospective data. Cytokine microarrays were analyzed from 4 patients with resistant to IVIG, 4 patients with responsive to IVIG and 4 healthy volunteers. Results During the training set, 409 patients with KD were enrolled, of whom 43 (10.5%) were resistant to initial IVIG treatment and 47 (11.49%) had coronary artery lesions (CALs). Serum levels of SAA were higher in the IVIG resistant group compared to the IVIG responsive group, (380.00 [204.40–547.25] vs 230.85 [105.40–490.00] mg/L; p = .008). The values of total bilirubin, C-reactive protein, neutrophils, alanine aminotransferase, aspartate aminotransferase, interleukin-6(IL-6), and procalcitonin were significantly higher in the IVIG-resistant group than in the IVIG-responsive group (p < .05); however, the lymphocytes, platelets, serum sodium levels, and duration of fever before IVIG therapy were significantly lower (p < .05). There was no significant difference in SAA levels between patients with KD with and without CALs. Binary logistic regression analysis showed that SAA (p = .008), neutrophils (p < .001), total bilirubin (p = .001), platelet count (p = .004), and serum sodium level (p = .019) were independent factors influencing IVIG resistance. The optimal cutoff value of SAA for IVIG resistance prediction was 252.45 mg/L, with a corresponding clinical sensitivity of 69.8% and specificity of 54.4%. Based on receiver operating characteristic (ROC) curve analyses, the area under the curve (AUC) of combined detection with these five indicators was 0.800, clinical sensitivity was 69.8%, and specificity was 76.2%. In the prospective data, the sensitivity, specificity, and accuracy of SAA for identifying IVIG resistance KD were 77.8%,69.0%, and 70.0%, respectively. Compared with IVIG- responsive group and healthy children, the levels of IL-6 was upregulated significantly in IVIG-resistant group through cytokine microarrays. Conclusions SAA may be a potential biomarker for predicting IVIG responsiveness to KD, Combined detection of SAA levels, total bilirubin, neutrophil count, platelet count, and serum sodium levels is superior to that of any other single indicator for predicting IVIG resistance in KD. And elevated SAA may accompany with IL-6 in KD patients, its use in clinical practice may be helpful for treatment management.

Intravenous immunoglobulin (IVIG) resistance was a major cause of coronary artery lesions in children with Kawasaki disease (KD). However, the cause of IVIG resistance in KD remains unknown. miR-221-3p has been confirmed involved in cardiovascular diseases and rheumatoid arthritis. The purpose of this study was to investigate the association between miR-221-3p and IVIG resistance in children with KD. Fifty-five KD patients and 29 healthy controls (HCs) were enrolled in this study. KD patients were divided into group of sensitive to IVIG (IVIG-response, n = 42) and group of resistant to IVIG (IVIG-resistance, n = 13), group of 10 KD patients with coronary artery lesions (CALs, KD-CALs) and group of 10 sex- and age-matched KD patients without CALs (KD-NCALs). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the levels of miR-221-3p. Compared with the HCs group, miR-221-3p were significantly increased in the KD group (p < 0.05), and the IVIG-resistance group had higher levels of miR-221-3p than those in the IVIG-response group (p < 0.05). CRP (C-reactive protein), PCT (procalcitonin), NLR (neutrophil-lymphocyte ratio) were positively correlated with miR-221-3p in KD patients. In addition, the group of IVIG resistance had a higher level of Kobayashi Score (p < 0.001). The receiver operating characteristic curve showed that miR-221-3p had a better value for diagnosis IVIG resistance in children with KD than Kobayashi Score with the AUC of 0.811 (95% CI, 0.672-0.951), 0.793 (95% CI, 0.618-0.968), respectively. Additionally, miR-221-3p was elevated (p < 0.05) and showed an AUC value of 0.83 (95% CI, 0.648-1.000, p < 0.05) for the prediction of the complication of coronary artery abnormalities in the group of KD with CALs. miR-221-3p might be involved in the pathogenesis of KD and IVIG resistance and miR-221-3p can be used as a new potential biomarker to predict IVIG resistance in children with KD.

To assess the risk factors of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) and to evaluate the performance of the three Japanese risk-scoring systems, namely the Kobayashi, Egami, and Sano scores in predicting IVIG resistance among the Indian patients. Prospective observational study on children admitted with KD at Institute of Child Health, Kolkata, over a period of 16months, from January 2019 to April 2020. The study included 70 KD patients all of whom were treated with IVIG. Clinical parameters, laboratory variables, and risk scores were compared between the IVIG-responsive and the IVIG-resistant groups. A total of 31.4% were IVIG non-responders. Skin rash was found to be significantly associated with IVIG-resistant KD. The IVIG-resistant group had higher total bilirubin, lower albumin, higher CRP levels, and higher ALT and AST levels. High Kobayashi score, high Egami score, and high Sano score were significantly associated with IVIG resistance, individually. Sano score had the highest sensitivity (81.8%) and Kobayashi score had the highest specificity (77.1%) in our cohort. The presence of skin rash, high total bilirubin, high CRP, high AST, high ALT, and low albumin were important predictors of IVIG resistance in our population. Among the three scores, Sano score is the most reliable in identifying potential non-responders to IVIG. But Sano score lacked good specificity. Therefore, Indian KD patients may need an exclusive scoring system to predict non-responsiveness to IVIG so that a more aggressive therapy can be instituted at the earliest. Key points • Early prediction of IVIG-resistant KD is necessary to limit cardiac injuries. • Sano score has high sensitivity to predict IVIG resistance in Indian population.

Background: Children with Kawasaki disease (KD) under 1-year old are at high risk for intravenous immunoglobulin (IVIG) resistance. The study was designed to explore the predictive measure of IVIG resistance in infants under 1-year old with KD.Methods: This study enrolled children under 1-year old suffering from KD in Peking University First Hospital and Wuhan Children's Hospital. All infants were divided into IVIG-responsive and IVIG-resistant groups. The differences in demographic characteristics, clinical features, and laboratory examinations were compared and the risk factors of IVIG resistant KD were analyzed. Furthermore, a scoring system was developed for predicting IVIG resistance in KD infants and an external validation was performed.Result: A total of 282 infants (194 boys, median age of 7.0 months) were enrolled in this study, of whom 23 children were IVIG-resistant. Compared with IVIG-responsive infants, those in the IVIG-resistant group had a high neutrophil-to-lymphocyte ratio (NLR), high platelet-to-lymphocyte ratio (PLR), high mean platelet volume-to-lymphocyte ratio (MPVLR) in peripheral blood, and low serum albumin, and low serum sodium before IVIG therapy (all P < 0.01). Multiple regression analysis indicated that high levels of peripheral NLR and MPVLR, and low levels of serum albumin and serum sodium were independent risk factors for IVIG resistant KD infants. A scoring system, which included peripheral NLR ≥ 2.69 (1 point), MPVLR ≥ 2.78 (1 point), serum albumin ≤ 30.7 g/L (1 point), and serum sodium ≤ 135.2 mmol/L (1 point), was established. A cut-off value of a total score of 2 points or higher yielded a sensitivity of 87.0% and a specificity of 78.4%, with an area under the curve of 0.891. External validation with clinical diagnostic standard showed that a cut-off value of total score of 2 points or higher for predicting the IVIG-resistance yielded a sensitivity of 70.0% and a specificity of 75.1%.Conclusion: For the first time, we proposed a predictive model of IVIG resistance in KD infants under 1-year old. The scoring system, which accounts for baseline peripheral NLR, MPVLR, and serum albumin and sodium, predicts with relatively high sensitivity and specificity for IVIG-resistant infants with KD under 1-year old.

ObjectiveThis systematic review and meta-analysis aimed to evaluate the relationship between the prognostic nutritional index (PNI) and intravenous immunoglobulin (IVIG) resistance and coronary artery lesion (CAL) in Kawasaki disease (KD).MethodsThe relevant literature was searched on PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar up to August 5, 2023. A pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under curve (AUC) were calculated to assess the predicted values of PNI in KD patients with IVIG resistance and CAL.ResultsA total of 8 articles containing 10 studies involving 7,047 participants were included. The pooled results revealed a pooled sensitivity of 0.44 (0.25–0.65), a pooled specificity of 0.87 (0.73–0.94), a pooled PLR of 3.4 (2.0–5.9), a pooled NLR of 0.65 (0.48–0.87), a pooled DOR of 5.26 (2.76–10.02), and a pooled AUC of 0.75 (0.71–0.78) in the diagnosis of KD with CAL. The pooled results suggested that a pooled sensitivity was 0.69 (0.60–0.77), specificity was 0.76 (0.69–0.82), PLR was 2.9 (2.1–4.1), NLR was 0.40 (0.29–0.56), DOR was 7.27 (3.89–13.59), and AUC was 0.79 (0.75–0.82) in the diagnosis of KD with IVIG resistance. The combined results revealed the pooled sensitivity was 0.63 (0.58–0.67), specificity was 0.82 (0.80–0.83), PLR was 3.09 (1.06–8.98), NLR was 0.38 (0.07–2.02), DOR was 8.23 (0.81–83.16) in differentiating KD from febrile patients. These findings demonstrated low sensitivity and relatively high specificity of PNI for KD, KD-CAL, and IVIG-resistant KD.ConclusionIn conclusion, this study was the first systematic review and meta-analysis of the diagnostic value of PNI in KD with IVIG resistance and CAL. The results suggested that PNI could be used as biomarkers for distinguish KD, KD with CAL, and KD with IVIG resistance.

Background: Patients with Kawasaki disease (KD) who have intravenous immunoglobulin (IVIG) resistance are at increased risk for development of coronary artery abnormalities. Although in Japan several risk scoring systems are able to predict patients with IVIG-resistant (KD), they do not accurately predict non-responders in other regions.Aim: The objectives of this study were to determine the predictors of IVIG resistance and coronary artery aneurysm (CAA) and to develop risk scoring systems for predicting IVIG-resistant KD in the Thai population.Methods: A total of 217 patients with KD between 2004 and 2014 were retrospectively reviewed. All patients including 116 with complete KD and 101 with incomplete KD were diagnosed and treated with 2 g/kg IVIG.Results: Twenty-six patients (85% male) with IVIG-resistant KD had a reduced platelet count and increased neutrophil-to-lymphocyte ratio compared with those with an IVIG response. Fifty-five patients with CAA eight weeks after diagnosis had a longer duration of fever (≥8 days) and increased platelet count (≥550 × 109/L) than those with non-CAA. Based on analysis by multivariate logistic regression, haematocrit ≤30%, platelet count ≤300 × 109/L, aspartate aminotransferase ≥40 U/L and neutrophil-to-lymphocyte ratio ≥3.2 were predictors of IVIG resistance. The new scoring system using these significant factors had a sensitivity of 80.8% and a specificity of 66.8% in identifying patients with IVIG resistance. Japanese scoring systems had low sensitivity and specificity.Conclusions: KD patients with reduced mean haemoglobin, increased AST level, increased neutrophil-to-lymphocyte ratio and reduced platelet count should be considered for conjunctive therapy such as a corticosteroid in combination with standard treatment. Duration of fever ≥8 days and platelet count ≥550 × 109/L were predictors of CAA. To prevent cardiovascular complications, patients should be treated promptly after KD has been diagnosed.

Kawasaki disease (KD) is a febrile vasculitis associated with mucocutaneous lesions, lymphadenopathy and cardiovascular events. Typical KD mostly occurs in children less than 5 years of age but atypical KD complicated with macrophage activation syndrome (MAS) or KD shock syndrome (KDSS) occurs in relatively older children, even adults. The etiology of KD remains unclear; however, the immune response is known to mediate by an autoinflammatory innate immune response associated with an imbalance of adaptive immunity showing augmented T helper 17 (Th17)/Th1 responses with higher IL-6, IL-10, IP-10, and IL-17 levels and reduced Th2/Treg responses with lower IL-4, IL-5, FoxP3, and TGFβ expression. This acute autoinflammatory vasculitis may be induced by an exogenous antigen derived from pathogen-associated molecular pattern (PAMP) or an endogenous antigen derived from damage-associated molecular pattern (DAMP). The altered immunity would manifest typical or atypical KD under genetic and environmental backgrounds. Some patients of KD (3–5%) are complicated with KDSS associated with over-production of nitric oxide, coagulopathy and shock symptom, and few patients (1–2%) are complicated with MAS, showing hemophagocytosis, thrombocytopenia, and hyperferritinemia. KD patients with these variant complications usually manifest intravenous immunoglobulin (IVIG) resistance and require additional anti-inflammatory medication. The immune reaction of KD reveals a kinetic progression for early administration of IVIG within 4 days of the illness did not provide a better outcome, and early administration of corticosteroids alone exacerbated the prognosis, but a combination of corticosteroids with IVIG provided the best treatment response. Further studies are proposed to identify the immunopathogenesis of IVIG-resistance, MAS and KDSS, to protect hosts from antigen exposure, and genetic susceptibility, and to combat MAS and/or KDSS by blockade of mechanistic biomarkers, anti-signal transduction, manipulations of host milieu, hit the brakes for immunosuppression and anti-hemophagocytosis.KeywordsKawasaki disease (KD)Kawasaki Disease Shock Syndrome (KDSS)Macrophage Activation Syndrome (MAS)Intravenous Immunoglobulin (IVIG) resistanceTh17/Treg imbalanceImmunotherapy

BackgroundIntravenous immunoglobulin (IVIG) resistance prediction remains substantial in Kawasaki disease (KD), with limited data on the predictive value of coagulation profile for IVIG resistance, particularly for repeated IVIG resistance. Therefore, the aim of our study was to testify the predictive validity of coagulation profile for both initial IVIG resistance and repeated IVIG resistance in KD.MethodsA total of 385 KD patients were prospectively recruited between April 2015 and May 2019. Coagulation and other profiles were evaluated between the IVIG‐responsive and IVIG‐resistant groups. Multivariate logistic regression analysis was applied to determine the association between coagulation profiles and IVIG resistance. ROC curves analysis was further performed to assess the validity of coagulation profiles in predicting both initial IVIG resistance and repeated IVIG resistance.ResultsProthrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen degradation products (FDPs), and D‐dimer were significantly increased in the initial IVIG‐resistant group with antithrombin III (ATIII) and thrombin time (TT) significantly reduced. Meanwhile, ATIII was declined markedly in repeated IVIG‐resistant patients. Multivariate logistic regression analysis showed that PT, APTT, D‐dimer, and ATIII were independent risk factors for predicting initial IVIG resistance and ATIII for predicting repeated IVIG‐resistant patients with KD. PT, APTT, D‐dimer, and ATIII cutoff values of 13.95 s, 41.15 s, 1.48 mg/L, and 89.5% yielded sensitivities of 73%, 32%, 71%, and 81%, and specificities of 55%, 88%, 62%, and 51% for predicting initial IVIG resistance, respectively. The cutoff value of ATIII for predicting repeated IVIG resistance was 68.5%, with sensitivity of 71% and specificity of 55%.ConclusionsKD patients who have hypercoagulation during the acute phase might be at higher risk of developing IVIG resistance.

We aimed to explore predictive measures for intravenous immunoglobulin (IVIG) resistance in children with Kawasaki disease (KD). Patients diagnosed with KD were enrolled in this study. Univariate analysis and multiple logistic regression were utilized to analyze the clinical features and laboratory results prior to IVIG-treatment of the two groups. Independent predictors of IVIG resistance were analyzed, and a predictive model for KD children with IVIG resistance was constructed. A total of 277 children with KD, 180 boys and 97 girls, aged 2-128 (median 23) months, were enrolled in the study. Compared with the IVIG-responsive group, the IVIG-resistant group had higher levels of the peripheral neutrophil count, mean platelet volume, mean platelet volume-to-lymphocyte ratio and C-reactive protein, and total serum bilirubin, but lower levels of peripheral lymphocyte count, serum albumin and serum prealbumin. Age (in months), peripheral neutrophil count, lymphocyte count and mean platelet volume and serum albumin were independent indicators for IVIG resistance by multivariate logistic regression analysis. A logistic regression model and a scoring system were set up, where cut-off values of -0.46 and 6.5 points yielded sensitivities of 83.9% and 77.4%, and specificities of 74.8% and 61.0%, respectively. The areas under the curve (AUC) were 0.808 in the logistic regression model, and 0.750 in the scoring system. Our model for predicting IVIG-resistant children with KD, involving age (months), peripheral neutrophil count, lymphocyte count and mean platelet volume and serum albumin prior to IVIG-treatment, is helpful for clinical prediction of children with IVIG-resistant KD.

We aimed to compare the ten different scores (by Kobayashi, Egami, Harada, Formosa, Sano, Piram et al., Wu et al., Yang et al., Tan et al., and Kanai et al.) to assess their performance in predicting IVIG resistance in Turkish children. Complete and incomplete KD patients diagnosed with KD at Hacettepe University between June 2007 and September 2019 were evaluated retrospectively. A total of 129 patients, 79 boys (61.2%), with a median age 36 (IQR 19.5-57.0) months were evaluated. Sixteen patients (12.4%) had IVIG resistance. Sensitivity was low for all the ten scores. Tan, Sano, and Egami predictive models had the highest specificity (97.3, 89.4, 86.7%, respectively). Almost all scoring systems distinguished the group of patients with low risk for IVIG resistance but could not differentiate IVIG-resistant patients. Multivariate analysis for the laboratory features showed that platelet count <300 × 109/L and GGT serum levels were independent risk factors for IVIG resistance (OR: 3.896; 95% CI: 1.054-14.404; p = 0.042 and OR: 1.008; 95% CI: 1.001-1.015; p = 0.050). The current scoring systems had a low sensitivity for predicting the risk for IVIG resistance in Turkish children. On the other hand, increased serum GGT levels and low platelet count were risk factors for predicting IVIG resistance. Intravenous immunoglobulin (IVIG) resistance may be observed in 10-20% of patients diagnosed with Kawasaki disease. Coronary artery involvement is more frequent in IVIG-resistant patients. It is important to predict the patients who might develop IVIG resistance to improve prognosis. The performance of the IVIG resistance predictive models in Kawasaki disease in our population is limited due to the low sensitivity.

Transcript abundance patterns in Kawasaki disease patients with intravenous immunoglobulin resistance

Background: C-reactive protein (CRP) to albumin ratio (CRP/Alb) has emerged as a novel marker of inflammation, but few studies have evaluated the role of CRP/Alb ratio in Kawasaki disease (KD). Coronary artery lesions (CAL) in children with KD is a major acquired heart disease. We aimed to assess the association between CRP/Alb ratio and CAL formation in children with KD.Methods: This retrospective study enrolled children diagnosed with KD and divided them into two groups, KD with CAL and KD without CAL. We compared the difference in gender, age, laboratory data, intravenous immunoglobulin (IVIG) resistance rate, and incidence of CAL between the two groups. Multivariable logistic regression analysis was used to assess the independent risk factors of CAL. We adopted receiver operating characteristic (ROC) curve analysis to determine the predictive ability of CRP/Alb ratio in predicting CAL.Results: In total, 410 KD patients were reviewed, with 143 in the KD with CAL group and 267 in the KD without CAL group. KD children with CAL had a higher CRP/Alb ratio than those without CAL (3.14 ± 3.17 vs. 2.12 ± 2.04, p < 0.001). Multivariable logistic regression analysis demonstrated that male gender (OR = 3.222, p < 0.001), incomplete KD (OR = 1.968, p = 0.031), greater platelet count (OR = 1.004, p < 0.001), higher CRP (OR = 0.982, p = 0.048), and higher CRP/Alb ratio (OR = 1.994, P = 0.016) were all independent risk factors for predicting CAL. KD children with a high CRP/Alb ratio (≥2.94) had a higher incidence rate of CAL and IVIG resistance than those with a low CRP/Alb ratio (<2.94) (49.6 vs. 28.7%, p < 0.001 and 11.6 vs. 3.5%, p = 0.001, respectively).Conclusions: This report is the first to show the role of CRP/Alb ratio in KD children. CRP/Alb ratio can serve as a novel predicting marker for CAL formation and IVIG resistance in KD.

Predicting intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) can aid early treatment and prevent coronary artery lesions. A clinically consistent predictive model was developed for IVIG resistance in KD. In this retrospective cohort study of children diagnosed with KD from January 1, 2016 to December 31, 2021, a scoring system was constructed. A prospective model validation was performed using the dataset of children with KD diagnosed from January 1 to June 2022. The least absolute shrinkage and selection operator (LASSO) regression analysis optimally selected baseline variables. Multivariate logistic regression incorporated predictors from the LASSO regression analysis to construct the model. Using selected variables, a nomogram was developed. The calibration plot, area under the receiver operating characteristic curve (AUC), and clinical impact curve (CIC) were used to evaluate model performance. Of 1975, 1,259 children (1,177 IVIG-sensitive and 82 IVIG-resistant KD) were included in the training set. Lymphocyte percentage; C-reactive protein/albumin ratio (CAR); and aspartate aminotransferase, sodium, and total bilirubin levels, were risk factors for IVIG resistance. The training set AUC was 0.825 (sensitivity, 0.723; specificity, 0.744). CIC indicated good clinical application of the nomogram. The nomogram can well predict IVIG resistance in KD. CAR was an important marker in predicting IVIG resistance in Kawasaki disease.

Background and Objectives: Most cases of Kawasaki disease (KD) occur between the ages of 6 months and 5 years. Differences in immunological reaction and CAL (coronary artery lesion) by the age subgroups classified according to the prevalence of KD and those particularly in the earlier life of KD should be investigated. Materials and Methods: The laboratory data of 223 infantile and 681 non-infantile KD cases from 2003 to 2018 at Korea University Hospital were retrospectively analyzed. Patients with KD were divided into infants and non-infants and further subdivided into four subgroups by age. The age-adjusted Z-values were compared among the subgroups. Febrile controls were identified as patients with fever for >5 days and who showed some of the KD symptoms. Results: IVIG (intravenous immunoglobulin) resistance at the age of 6 months or less was significantly lower than that at the ages of 7–12 months and 13–60 months (respectively, p < 0.05). The significant risk factors for CAL in total KD patients were age, incomplete KD, post-IVIG fever, IVIG resistance, convalescent Z-eosinophil, and subacute platelet (p < 0.05). The significant risk factors for CAL at the age of 6 months or less were IVIG resistance, acute Z-neutrophil, subacute Z-neutrophil, subacute NLR (neutrophil to lymphocyte ratio), and subacute platelet (respectively, p < 0.05). Conclusion: Younger age and incomplete presentation in KD can be independent risk factors for CAL. The immune reactions of KD at a younger age are more tolerated compared with those at older ages during the acute phase. The immune response at the age of 6 months or less showed immune tolerance in terms of incomplete presentation and IVIG responsiveness. The risk factors such as IVIG resistance, subacute platelet, subacute NLR, and acute or subacute Z-neutrophil at the age of 6 months or less can be very useful parameters to predict CAL in young, incomplete KD.