OBJECTIVES: To study the expression of interleukin-17A (IL-17A) in the serum of children with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) and its clinical significance. METHODS: A total of 143 children with KD who were hospitalized in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from June 2021 to June 2022 were enrolled in this prospective study, among whom 115 had IVIG-sensitive KD and 28 had IVIG-resistant KD. After matching for sex and age, 110 children with acute respiratory infectious diseases (fever time ≥5 days but without KD) were enrolled as the control group. The enzyme-linked immunosorbent assay was used to measure the serum level of IL-17A. The levels of white blood cell count (WBC), neutrophil count (NE), platelet count, erythrocyte sedimentation rate, and C-reactive protein (CRP) were measured. The receiver operating characteristic curve was plotted to analyze the value of WBC, NE, CRP, and IL-17A in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis was used to evaluate the predictive factors for resistance to IVIG in children with KD. RESULTS: Before IVIG treatment, the KD group had a significantly higher serum level of IL-17A than the control group (P<0.05), and the children with IVIG-resistant KD had a significantly higher serum level of IL-17A than those with IVIG-sensitive KD (P<0.05). The receiver operating characteristic curve analysis showed that WBC, NE, CRP, and IL-17A had an area under the curve of 0.718, 0.741, 0.627, and 0.840, respectively, in the prediction of IVIG-resistant KD. With serum IL-17A ≥44.06 pg/mL as the cut-off value, IL-17A had a sensitivity of 84% and a specificity of 81% in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis showed that a high serum level of IL-17A was a predictive factor for resistance to IVIG in children with KD (OR=1.161, P=0.001). CONCLUSIONS Serum IL-17A levels are elevated in children with IVIG-resistant KD, and serum IL-17A level (≥44.06 pg/mL) may have a predictive value for resistance to IVIG in children with KD.
Humans ; Child ; Infant ; Aged, 80 and over ; Immunoglobulins, Intravenous/therapeutic use* ; Mucocutaneous Lymph Node Syndrome/drug therapy* ; Interleukin-17 ; Clinical Relevance ; Prospective Studies ; C-Reactive Protein/analysis* ; Retrospective Studies

OBJECTIVES: To summarize the clinical features of liver damage in children in the acute stage of Kawasaki disease (KD), and to investigate the clinical value of liver damage in predicting coronary artery lesion and no response to intravenous immunoglobulin (IVIG) in children with KD. METHODS: The medical data were collected from 925 children who were diagnosed with KD for the first time in Beijing Children's Hospital from January 1, 2016 to December 31, 2017. According to the presence or absence of abnormal alanine aminotransferase (ALT) level on admission, the children were divided into a liver damage group (n=284) and a non-liver damage group (n=641). A logistic regression analysis was used to investigate the clinical value of the indicators including liver damage in predicting coronary artery lesion and no response to IVIG in children with KD. RESULTS: Compared with the non-liver damage group, the liver damage group had a significantly earlier admission time and significantly higher serum levels of inflammatory indicators (P<0.05). The liver damage group had a significantly higher incidence rate of coronary artery lesion on admission than the non-liver damage group (P=0.034). After initial IVIG therapy, the liver damage group had a significantly higher proportion of children with no response to IVIG than the non-liver damage group (P<0.001). In children with KD, coronary artery lesion was associated with the reduction in the hemoglobin level and the increases in platelet count, C-reactive protein, and ALT (P<0.05), and no response to IVIG was associated with limb changes, the reduction in the hemoglobin level, the increases in platelet count, C-reactive protein, and ALT, and coronary artery lesion (P<0.05). CONCLUSIONS Compared with those without liver damage, the children in the early stage of KD with liver damage tend to develop clinical symptoms early and have higher levels of inflammatory indicators, and they are more likely to have coronary artery lesion and show no response to IVIG treatment.
C-Reactive Protein/analysis* ; Child ; Coronary Vessels/pathology* ; Hemoglobins/analysis* ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Liver Diseases ; Mucocutaneous Lymph Node Syndrome/drug therapy* ; Retrospective Studies

Immunoglobulin G4 (IgG4)-related dacryoadenitis and sialoadenitis (IgG4-DS) are part of a multiorgan fibroinflammatory condition of unknown etiology termed IgG4-related disease (IgG4-RD), which has been recognized as a single diagnostic entity for less than 15 years. Histopathologic examination is critical for diagnosis of IgG4-RD. CD4+ T and B cells, including IgG4-expressing plasma cells, constitute the major inflammatory cell populations in IgG4-RD and are thought to cause organ damage and tissue fibrosis. Patients with IgG4-RD who have active, untreated disease exhibit significant increase of IgG4-secreting plasmablasts in the blood. Considerable insight into the immunologic mechanisms of IgG4-RD has been achieved in the last decade using novel molecular biology approaches, including next-generation and single-cell RNA sequencing. Exploring the interactions between CD4+ T cells and B lineage cells is critical for understanding the pathophysiology of IgG4-RD. Establishment of pathogenic T cell clones and identification of antigens specific to these clones constitutes the first steps in determining the pathogenesis of the disease. Herein, the clinical features and mechanistic insights regarding pathogenesis of IgG4-RD were reviewed.
B-Lymphocytes ; Clone Cells ; Dacryocystitis ; Diagnosis ; Fibrosis ; Humans ; Immunoglobulins ; Molecular Biology ; Plasma Cells ; Sequence Analysis, RNA ; Sialadenitis ; T-Lymphocytes

Adult ; Aged ; Aged, 80 and over ; Air Pollutants ; adverse effects ; Blood Chemical Analysis ; Coke ; adverse effects ; Environmental Exposure ; Female ; Humans ; Immunoglobulins ; metabolism ; Male ; Middle Aged ; Polycyclic Aromatic Hydrocarbons ; adverse effects ; Young Adult

PURPOSE: Intravenous immunoglobulin (IVIG) is the standard treatment for Kawasaki disease (KD). However, there is still no standard treatment for IVIG-resistant KD. This study aimed to evaluate the efficacy of low-dose methotrexate (MTX) as a treatment for IVIG-resistant KD. MATERIALS AND METHODS: We retrospectively analyzed 10-year data for patients with IVIG-resistant KD who were administered MTX at Severance Children's Hospital. RESULTS: The subjects included 75 patients with KD aged 5 months to 9.2 years who had been administered MTX. Their maximum body temperatures decreased significantly within 24 h of therapy. The patients' C-reactive protein levels were significantly lower 1 week after administering the first dose of MTX than those before treatment. No adverse effect for MTX was observed. CONCLUSION: MTX treatment of IVIG-resistant KD resulted in rapid defervescence, improvement of clinical symptoms, and normalization of acute-phase reactants in all patients. Thus, MTX could be a candidate treatment for IVIG-resistant KD.
C-Reactive Protein/analysis ; Child ; Child, Preschool ; Coronary Vessels/pathology ; Demography ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Infant ; Male ; Methotrexate/administration & dosage ; Methotrexate/therapeutic use ; Mucocutaneous Lymph Node Syndrome/blood ; Mucocutaneous Lymph Node Syndrome/drug therapy ; Retrospective Studies ; Steroids/therapeutic use ; Treatment Outcome

PURPOSE: The immunological characteristics of young Korean children with walnut (WN) allergy and the influence of different cooking methods on WN proteins have not been evaluated to date. This study aimed to evaluate the major WN allergens identified among Korean children, together with changes in WN antigenicity caused by common cooking methods. METHODS: We enrolled children under the age of 13 years with WN serum-specific immunoglobulin (Ig) E concentrations. The protein fractions of dry-fried and boiled WN extracts were compared with those of raw WNs using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), 2-dimentional gel electrophoresis (2DE) and a proteomic analysis using electrospray ionization (liquid chromatography-mass spectrometry [LC-MS]). An immunoblotting analysis was conducted to examine IgE reactivity toward raw WNs using serum samples from 6 children with a clinical WN allergy. To determine the processed WN proteins with IgE-binding capacity, a 2D-immunoblotting analysis was performed using the pooled sera of 20 WN-sensitized children. RESULTS: Protein bands from raw WNs were identified at 9, 16, 28, 52, 58, and 64 kDa via SDS-PAGE. The 9- and 16-kDa protein bands were enhanced by boiling, whereas the 52- and 64-kDa bands were considerably diminished. On LC-MS analysis, of the 66 IgE-binding proteins present in raw WNs, 57 were found in dry-fried WNs, but only 4 in boiled WNs. The sera of 5 out of 6 participants reacted with the 52-kDa protein bands and those of 4 out of 6 participants reacted with the 16- and 28-kDa protein bands, respectively. Meanwhile, a 2D-immunoblotting result confirmed the presence of different binding patterns among children who consumed cooked WNs. CONCLUSIONS: The protein profile of boiled WNs is substantially different from that of raw WNs. However, 4 proteins including prolamins remained stable after dry-frying or boiling. Further studies are needed to evaluate the clinical relevance of these findings.
Allergens ; Child* ; Cooking ; Electrophoresis ; Electrophoresis, Polyacrylamide Gel ; Humans ; Hypersensitivity ; Immunoblotting ; Immunoglobulin E ; Immunoglobulins* ; Juglans* ; Prolamins ; Sodium Dodecyl Sulfate ; Spectrum Analysis

BACKGROUND: The zoonotic disease Q fever is caused by Coxiella burnetii and usually affects high-risk human populations. We conducted a serological survey of dairy cattle farmers in Korea to determine seroreactivity and identify risk factors for C. burnetii infection. METHODS: This cross-sectional study included 1,824 of 7,219 dairy cattle farms (25.3%) in the study region. The selected dairy cattle farmers visited the nearest public health centers or branches with completed questionnaires. Serum samples from the farmers were tested using an indirect immunofluorescence assay to detect phase II C. burnetii immunoglobulin (Ig) G or M antibodies. RESULTS: A total of 1,222 dairy cattle farmers from 784 dairy cattle farms (43.0%) participated in this study, and 11.0% (134/1,222) exhibited seroreactivity, defined as a phase II antigen IgG or IgM titer ≥ 1:16. In the multivariate analysis, male sex, residence in Gyeonggi Province, a larger herd size, and ocular/oral contact with birth products during calf delivery were significantly associated with a higher risk of C. burnetii infection. Furthermore, the risk was significantly lower among farmers who always wore protective gloves while cleaning cattle excretion, compared to those who sometimes or rarely wore protective gloves. CONCLUSION: Dairy cattle farmers should exercise caution by avoiding ocular/oral contact with birth products during calf delivery and by using protective equipment (including gloves).
Agriculture ; Animals ; Antibodies ; Cattle* ; Coxiella burnetii* ; Coxiella* ; Cross-Sectional Studies ; Farmers* ; Fluorescent Antibody Technique, Indirect ; Gloves, Protective ; Gyeonggi-do ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Immunoglobulins ; Korea* ; Male ; Multivariate Analysis ; Parturition ; Public Health ; Q Fever* ; Risk Factors* ; Serologic Tests ; Zoonoses

PURPOSE: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is an emerging immune response molecule related to T-cell anergy. There has been tremendous interest in breast cancer targeting immune checkpoint molecules, especially in the triple-negative breast cancer (TNBC). This study was designed to investigate TIM-3 expression on tumor infiltrating lymphocytes (TILs), its relationships with clinicopathological para-meters and expression of programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), and its prognostic role. METHODS: Immunohistochemistry on tissue microarray blocks produced from 109 samples of invasive ductal carcinoma type TNBC was performed with antibodies toward TIM-3, PD-1, PD-L1 and breast cancer-related molecular markers. Associations between their expression and clinicopathological parameters as well as survival analyses were performed. RESULTS: TIM-3 was expressed in TILs from all 109 TNBCs, consisting of 17 cases ( < 5%), 31 cases (6%–25%), 48 cases (26%–50%), and 13 cases (>51%). High TIM-3 was significantly correlated with younger patients (p=0.0101), high TILs (p=0.0029), high tumor stage (p=0.0018), high PD-1 (p=0.0001) and high PD-L1 (p=0.0019), and tended to be associated with higher histologic grade, absence of extensive in situ components and microcalcification. High TIM-3 expression was significantly associated with a combinational immunophenotype group of high PD-L1 and high PD-1 (p < 0.0001). High TIM-3 demonstrated a significantly better disease-free survival (DFS) (p < 0.0001) and longer overall survival (OS) (p=0.0001), together with high TILs and high PD-1. In univariate survival analysis, high TIM-3 showed reduced relapse risk (p < 0.0001) and longer OS (p=0.0003), together with high PD-1 expression. In multivariate analysis, high TIM-3 was statistically significant in predicting prognosis, showing better DFS (hazard ratio [HR], 0.0994; 95% confidence interval [CI], 0.0296–0.3337; p=0.0002) and longer OS (HR, 0.1109; 95% CI, 0.0314–0.3912; p=0.0006). CONCLUSION: In this study, we demonstrate that TIM-3 expression is an independent positive prognostic factor in TNBC, despite its association with poor clinical and pathologic features.
Antibodies ; Breast ; Breast Neoplasms ; Carcinoma, Ductal ; Disease-Free Survival ; Humans ; Immunoglobulins* ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating* ; Mucin-3* ; Mucins* ; Multivariate Analysis ; Prognosis ; Recurrence ; T-Lymphocytes* ; Triple Negative Breast Neoplasms*

OBJECTIVETo study the values of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in predicting the sensitivity to intravenous immunoglobulin (IVIG) in Kawasaki disease (KD).

METHODSA retrospective cohort study was conducted in 404 children with newly diagnosed KD. The data on routine blood tests, NLR, and PLR were collected before and after IVIG treatment. The receiver operating characteristic (ROC) curve was used to determine the cut-off values of NLR and PLR in predicting the insensitivity to IVIG. A logistic regression analysis was used to identify independent predictive factors for insensitivity to IVIG.

RESULTSOf all patients, 31 were insensitive to IVIG. Compared with the IVIG sensitivity group, the IVIG insensitivity group had a significantly higher incidence rate of coronary artery ectasia (P<0.01), a shorter course of disease when IVIG therapy was initiated (P<0.05), and significantly higher NLR, PLR, and C-reactive protein (CRP) level before and after treatment (P<0.05). The optimal cut-off values for NLR and PLR to predict IVIG insensitivity were 4.36 and 162 before IVIG treatment and 1.45 and 196 after treatment. The multivariate regression analysis showed that the course of disease before IVIG treatment, CRP before IVIG treatment, and NLR and PLR before and after IVIG treatment were independent predictive factors for IVIG insensitivity.

CONCLUSIONSNLR and PLR can be used to predict IVIG insensitivity in children with KD.

Blood Platelets ; C-Reactive Protein ; analysis ; Child, Preschool ; Female ; Humans ; Immunoglobulins, Intravenous ; therapeutic use ; Infant ; Logistic Models ; Lymphocytes ; Male ; Mucocutaneous Lymph Node Syndrome ; blood ; drug therapy ; Neutrophils

BACKGROUND: Allergens tend to sensitize simultaneously. Etiology of this phenomenon has been suggested to be allergen cross-reactivity or concurrent exposure. However, little is known about specific allergen sensitization patterns. OBJECTIVE: To investigate the allergen sensitization characteristics according to gender. METHODS: Multiple allergen simultaneous test (MAST) is widely used as a screening tool for detecting allergen sensitization in dermatologic clinics. We retrospectively reviewed the medical records of patients with MAST results between 2008 and 2014 in our Department of Dermatology. A cluster analysis was performed to elucidate the allergen-specific immunoglobulin (Ig)E cluster pattern. RESULTS: The results of MAST (39 allergen-specific IgEs) from 4,360 cases were analyzed. By cluster analysis, 39items were grouped into 8 clusters. Each cluster had characteristic features. When compared with female, the male group tended to be sensitized more frequently to all tested allergens, except for fungus allergens cluster. CONCLUSION: The cluster and comparative analysis results demonstrate that the allergen sensitization is clustered, manifesting allergen similarity or co-exposure. Only the fungus cluster allergens tend to sensitize female group more frequently than male group.
Allergens ; Cluster Analysis* ; Dermatology ; Female ; Fungi ; Humans ; Immunoglobulins ; Korea* ; Male ; Mass Screening ; Medical Records ; Retrospective Studies