Jin-Kyong Chun

Predicting Factors for Refractory Kawasaki Disease

Background and Objectives About 10-15% of Kawasaki disease (KD) is refractory to intravenous immunoglobulin (IVIG) therapy. This study was designed to investigate the predicting factors for refractory KD. Subjects and Methods We reviewed retrospectively the clinical records of 77 patients with typical KD admitted at Wonju Christian Hospital from January, 2005, to December, 2008. The variance of laboratory and demographic parameters between the IVIG-responsive group and IVIG-resistant group were analyzed. Thirteen patients with urinary tract infections were randomly collected as a febrile control group. Results Among 77 patients diagnosed with complete KD, 13 patients (16.9%) were IVIG-resistant. The febrile period and hospital days were significantly longer in the IVIG-resistant group than IVIG-responsive group (p<0.001, p=0.002). Serum levels of albumin and sodium were significantly lower in the IVIG-resistant group (p=0.025). The Kobayashi score could differentiate these two groups (p=0.015). Fewer lymphocytes was observed during the subacute phase in the IVIG-resistant group (p=0.032). Coronary arterial dilatations (CADs) were observed in 10.9% (7/64) of IVIG-responders and 38.5% (5/13) of IVIG-resistant patients (p=0.038). Conclusion The percentage of neutrophils and lymphocytes in patients with KD, in addition to known risk factors for refractory KD, may help predict IVIG-resistance in patients with KD.

Elevated anti-α-enolase antibody levels in Kawasaki disease

Objective: By functioning as a heat‐shock protein (HSP), α‐enolase has an important role in the pathophysiology of multivariant vasculitis. Kawasaki disease (KD) is a type of vasculitis occurring primarily in children. The role of α‐enolase in KD was assessed by measuring anti‐α‐enolase antibody (Ab) titres in patients with KD and the usefulness of anti‐α‐enolase Ab as a diagnostic tool in atypical KD patients was evaluated. Methods: Anti‐α‐enolase Ab titres were measured by using an enzyme‐linked immunosorbent assay (ELISA) in seven normal control patients, nine febrile control patients and 14 KD patients (10 typical KD, four atypical KD). A standard deviation (SD) of 3 above the mean of the normal control group was considered to be positive reactivity. Western blotting using recombinant human α‐enolase was performed in four KD patients and three normal controls. Results: With the positive reactivity limited to +3 SD over the mean (>0.6), 10 out of 14 patients (71%) were positive at the acute onset and 12 out of 14 patients (85.7%) were positive before discharge. In total, 12 out of 14 patients (85.7%) were positive either at acute onset or before discharge. All four atypical KD patients showed positive reactivity. Specific positive bands against recombinant human α‐enolase were detected by western blotting in all four KD patients, but no reactivity was seen in three patients with normal controls. Conclusion: This is the first study to demonstrate that autoantibodies against the α‐enolase are present in the sera of KD patients. We suggest that anti‐α‐enolase Ab should be a good candidate for a diagnostic tool in atypical KD.

Prevalence and patterns of anti‐nuclear antibodies in Korean children with juvenile idiopathic arthritis according to ILAR criteria

Objectives: To investigate the prevalence and patterns of anti‐nuclear antibodies (ANA) in different subtypes of juvenile idiopathic arthritis (JIA) according to the International League of Associations for Rheumatology (ILAR) criteria. Methods: One hundred and fifty‐three Korean patients (M:F 83:70) with JIA were followed between 1990 and 2006 and were tested for ANA by an indirect immunofluorescence method using HEp‐2 cells as the substrate. ANA tests were repeated in 37 patients during the course of the disease. The median age at onset was 7.5 years (range 0.8–15.9 years). Results: ANA were positive in 50 (33%) of the 153 patients at a dilution of 1:40 or higher (>1:40 in 70%, >1:80 in 2%, >1:160 in 16%, >1:320 in 2%, and >1:640 in 10%). The patterns of immunofluorescence staining were homogeneous in 50%, speckled in 38%, nucleolar in 8%, and centromere in 4%. ANA titres were decreased in 25 (68%) of the 37 patients, and the nuclear fluorescence patterns changed in 14 (38%) during follow‐up. ANA seropositivity was associated with female sex (p<0.0001), negative HLA‐B27 (p = 0.01), and a persistently elevated erythrocyte sedimentation rate (ESR) at follow‐up (p = 0.014). Furthermore, a high ANA titre (>1:160) was associated with a poor clinical outcome (active patients at follow‐up) (p = 0.005). Conclusions: ANA may be an important marker of disease activity in patients with JIA. ANA titres tend to decrease during disease remission but the fluorescence patterns do not appear to be related to disease activity or clinical outcome.

Evaluation of new hemagglutinin-based rapid antigen test for influenza A pandemic (H1N1) 2009

BACKGROUND A new rapid antigen test (RAT), based on hemagglutinin, was developed for the improvement of influenza A pandemic (H1N1) 2009 detection. OBJECTIVE To evaluate the performance of the new RAT for the diagnosis of influenza A pandemic (H1N1) 2009. STUDY DESIGN The new RAT included 2009 H1N1 hemagglutinin-based band and influenza A and influenza B nucleoprotein-based bands. During the period from November 24, 2009 to December 14, 2009, 948 patients underwent the new RAT and real-time reverse transcriptase polymerase chain reaction (rRT-PCR) at the same time. The result of the new RAT was compared with that of rRT-PCR, and the results of hemagglutinin-based and nucleoprotein-based antigen tests were compared. RESULT Among the 260 patients confirmed by rRT-PCR, 153 (58.8%) were positive in the nucleoprotein-based antigen test, and 182 (70.0%) were positive in the hemagglutinin-based antigen test. These results show that the new hemagglutinin-based antigen test was more sensitive than the nucleoprotein-based antigen test for the detection of influenza A pandemic (H1N1) 2009 (p<0.001, the McNemar test). CONCLUSION The new hemagglutinin-based antigen test improved the sensitivity of diagnosis for influenza A pandemic (H1N1) 2009 and it might be helpful for the diagnosis of influenza A pandemic (H1N1) 2009.

Elevated Serum Levels of IL-21 in Kawasaki Disease

Purpose The serum level of immunoglobulin (Ig)E has been reported to be elevated in patients with Kawasaki disease (KD). We investigated whether interleukin (IL)-21, rather than IL-4, could be related to elevated serum levels of IgE in KD. Methods Sera from 48 patients with KD and 12 controls with high fever were collected to determine the level of IgE using an immunoassay system and the levels of IL-4 and IL-21 were determined using enzyme-linked immunosorbent assay kits. Results The median IL-21 level of KD patients was significantly elevated, at 499.5 pg/mL (range: <62.5-1,544 pg/mL), whereas that of controls was <62.5 pg/mL (<62.5-825 pg/mL; P<0.001). The median IL-4 level of KD patients was not elevated (4.0 pg/mL; 2.1-7.6 pg/mL). The median level of total IgE in KD patients was 58.0 IU/mL (5-1,109 IU/mL). No statistically significant correlation was found between IL-21 and total IgE levels (Spearmans R=0.2; P=0.19). Conclusions Patients with KD have elevated levels of IL-21 in the serum. IL-21 may play a role in the pathogenesis of KD.

Increased serum levels of macrophage migration inhibitory factor in patients with Kawasaki disease

Objective: To determine whether serum levels of macrophage migration inhibitory factor (MIF) increase in patients with Kawasaki disease (KD) and also correlate with other inflammatory indices. Methods: Serum samples from 10 patients with KD, 15 normal healthy subjects, and seven febrile control subjects were assayed for MIF by enzyme‐linked immunosorbent assay (ELISA). Results: There was a significant increase in the serum levels of MIF in the acute stage of KD [113.06 (range 20.6–157.36) ng/mL] compared with those in the subacute stage [28.11 (8.57–143.48) ng/mL, p<0.01], normal controls [12.95 (8.40–18.67) ng/mL, p<0.001], and febrile controls [36.58 (21.31–59.67) ng/mL, p = 0.01]. The increase in MIF correlated with an increase in interleukin‐6 (IL‐6) (r = 0.52, p = 0.047). Conclusion: MIF may be a useful marker in the acute stage of KD and may provide important clues to the pathogenesis of this disease.