[Show abstract][Hide abstract] ABSTRACT: Background:
The responses of immunological factors to different subtypes of Kawasaki disease (KD) remain poorly understood.
We recruited 388 patients with KD, 160 patients with infectious febrile disease and 85 normal children who served as control subjects. Both the levels and percentages of T lymphocyte subsets, natural killer cells (NK cells) and B cells were analyzed via flow cytometry. The levels of serum IgG, IgM, IgA and C3, C4 were assessed via velocity scatter turbidimetry.
The most significant differences noted between the patients with infectious febrile disease and the normal children were the elevated levels of B cells, C3 and the ratio of CD4/CD8, and the decreased levels of CD8+ T cells and NK cells, as well as the moderate increase in the absolute value of the CD3+ cells. The decreased T cell levels and the elevated B cell levels were helpful in distinguishing typical KD from atypical KD; the elevated T cell levels, the elevated NK cell and B cell levels and the decreased B cell levels were helpful in predicting the effectiveness of IVIG; low C3 and C4 levels were linked with prodromal infections.
Lymphocytes subsets and complement markers may be useful in differentiating among the different subtypes of KD and in helping clinicians understand the pathophysiology of KD.
[Show abstract][Hide abstract] ABSTRACT: Objective
To explore the association of congenital heart disease (CHD) with serum levels of Ghrelin, tumor necrosis factor-alpha (TNF-α) and IL-6.Method
Sixty three children with CHD, hospitalized between Jan. 2012 and Sep. 2014 at Wuhan Women and Children's Health Care Center, were selected as experimental group. Additionally, 28 healthy individuals who had physical examinations at this hospital were selected as control group. Enzyme linked immunosorbent assays (ELISA) was employed to determine serum Ghrelin, TNF-α and IL-6 levels. SPSS 18.0 and Comprehensive Meta-analysis 2.0 were performed for our data analysis.ResultsThere was significant difference in weight, height and body mass index (BMI) (all P < 0.05) but not in age and sex (both P > 0.05) in cyanotic congenital heart disease (CCHD), acyanotic congenital heart disease (ACHD) and control groups. One-way analysis of variance suggested serum Ghrelin, TNF-α and IL-6 levels in both CCHD and ACHD groups were higher compared to control group (all P < 0.05). Pearson correlation analysis indicated, among the three groups, there was a correlation between serum Ghrelin levels and BMI (all P < 0.05), and TNF-α levels were negatively, IL-6 levels positively correlated with BMI (all P < 0.05). Meta-analysis further demonstrated that serum Ghrelin, TNF-α and IL-6 levels in both CCHD and ACHD groups were higher than control group (all P < 0.05).Conclusion
Our study provided conclusive evidence that serum Ghrelin, TNF-α and IL-6 levels are elevated in children with CHD, and play a potential role in development and progression of CHD. This article is protected by copyright. All rights reserved.
Pediatrics International 08/2015; DOI:10.1111/ped.12773 · 0.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study the association of single nucleotide polymorphisms (SNPs, rs223895 and rs223899) in TARC/CCL17 gene with Kawasaki disease (KD) and its clinical characteristics in Han children from Central China.
A case-control study was performed on 218 children with KD and 248 normal control children. The genotypes of SNPs (rs223895 and rs223899) in TARC/CCL17 gene were determined by polymerase chain reaction-restriction fragment length polymorphism. The association between the SNPs in TARC/CCL17 gene and the clinical characteristics of KD was assessed.
There were significant differences in the genotype (CC, CT, TT) and allele frequencies of SNP rs223895 between children with KD and controls (P<0.05), and C allele was a risk factor (OR=1.397). However, no significant differences were found between the two groups in the genotype and allele frequencies of SNP rs223899. Compared with those with other genotypes (CT+TT) of SNP rs223895, patients with CC genotype had significantly lower hemoglobin (Hb) and albumin (Alb) levels (P<0.05) and a significantly higher erythrocyte sedimentation rate (ESR) (P<0.05).
The SNP rs223895 in TARC/CCL17 gene is associated with the susceptibility to KD, and C allele is a risk factor. Moreover, SNP rs223895 may influence the levels of Hb, Alb, and ESR.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 07/2015; 17(7):668-671. DOI:10.7499/j.issn.1008-8830.2015.07.005
[Show abstract][Hide abstract] ABSTRACT: IgA vasculitis (IgAV), previously named as Henoch-Schönlein purpura, is the most common systematic vasculitis with unknown etiology. Lack of appropriate study system and/or animal model limits the understanding of its molecular pathogenesis and hinders the identification of targets for rational therapy, especially for its long-term complication, IgAV nephritis (IgAVN). In this study, we applied comparative analysis of serum proteomes to obtain an insight about disease pathogenesis. This study has utilized high sensitivity nanoscale ultra performance liquid chromatography-mass spectrometry (nanoLC-MS/MS) to investigate the alterations in serum proteomic profiles in patients with IgAV (n=6), IgAVN (n=6) and healthy subjects (n=7). The differentially expressed proteins were subjected to functional pathway analysis by PANTHER and DAVID software. We identified 107 differentially expressed proteins among three different groups, and functional analysis suggested that, in addition to earlier reported pathways, such as acute phase response, immune response, complement and blood coagulation pathways, hemostasis and Wnt signaling pathway were probably involved in pathogenesis of IgAV. A few differentially abundant proteins identified, such as C4a, serum amyloid A, angiotensinogen, and kininogen 1, were further validated by ELISA. More importantly, we found that angiotensinogen concentration is correlated with IgAVN and could be used as a potential marker for the progression of IgAV. This is the first report of analyzing the proteomic alterations in IgAV patients and the differentially proteins identified in this study may enhance understanding of the pathology of IgAV and a few of them may be used to monitor disease progression.
PLoS ONE 06/2015; 10(6):e0130536. DOI:10.1371/journal.pone.0130536 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the expression of soluble intercellular adhesion molecule-1 (sICAM-1) and itd significance in children with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD).
A total of 271 children with KD who received IVIG treatment (including 252 IVIG-sensitive cases and 19 IVIG-resistant cases) were selected in the study; 78 of the 271 children had coronary artery dilation. Thirty-six age-matched healthy children were selected as the control group. Plasma sICAM-1 levels were measured using enzyme-linked immunosorbent assay. White blood cell count (WBC), neutrophil count, C-relative protein (CRP), aspartate aminotransferase(AST), serum sodium, and serum potassium were measured by laboratory tests.
Before IVIG treatment, the IVIG-sensitive cases and IVIG-resistant cases had significantly higher sICAM-1 levels than the control group (P<0.05), and the IVIG-resistant cases had significantly higher sICAM-1 levels than the IVIG-sensitive cases (P<0.05). After 24-48 hours of IVIG treatment, the IVIG-resistant cases had significantly higher sICAM-1 levels than the IVIG-sensitive cases (P<0.05). Before IVIG treatment, among the IVIG-sensitive cases, the sICAM-1 level was significantly higher in those with coronary artery dilation than in those without coronary artery dilation (P<0.05); among the IVIG-resistant cases, the sICAM-1 level was significantly higher in those with coronary artery dilation than in those without coronary artery dilation (P<0.05). In the IVIG-resistant cases, sICAM-1 level was positively correlated with WBC (before and after treatment) (r=0.7562, P<0.01; r=0.8435, P<0.01) and CRP (after treatment) (r=0.8936, P<0.01).
High sICAM-1 level may be used as a risk factor for resistance to IVIG and coronary artery dilation in children with KD.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 12/2013; 15(12):1109-12. DOI:10.7499/j.issn.1008-8830.2013.12.018
[Show abstract][Hide abstract] ABSTRACT: Henoch-Schönlein purpura (HSP) is the most common form of systemic vasculitis of unknown etiology. This study aimed at reviewing published studies investigating the association of genetic polymorphisms with HSP and its severity. We systematically reviewed all published data on genetic risk factors for HSP by searching MEDLINE. We also performed a meta-analysis of association studies of HLA-DRB1-01, 07, and 11, angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) polymorphism. We identified 45 studies investigating polymorphisms in 39 genes in association with HSP and/or its severity. Most of these genes are involved in immunological and/or inflammatory responses or vasomotor regulation. Most results were negative. The most convincing finding is the association of HLA-DRB1*01, 07, and 11 with HSP susceptibility. The overall odds ratios (ORs) for the three loci were significant for HSP: HLA-DRB1*01 (OR = 1.805, 95 % CI 1.259-2.588, p = 0.0012); HLA-DRB1*07 (OR = 0.671, 95 % CI 0.469-0.961, p = 0.058); HLA-DRB1*11 (OR = 2.001, 95 % CI 1.50-2.67, p = 0.027). Genetic regulation of endothelial function, such as polymorphisms in genes coding rennin-angiotensin system (RAS) components, endothelial nitric oxide synthases, Inter-Cellular Adhesion Molecule 1, and vascular endothelial growth factor, could also confer effect on HSP. In addition, MEFV, whose mutations cause familial Mediterranean fever, could be an important candidate gene for HSP. Further large studies are required to investigate the association between genetic polymorphisms and HSP. Alternative approaches, such as genome-wide association study, are necessary to help to identify genetic risks for HSP.
Rheumatology International 01/2013; 33(6). DOI:10.1007/s00296-012-2661-4 · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Henoch-Schönlein purpura nephritis (HSPN) is the most serious long-term complication of Henoch-Schönlein purpura and aberrant galactosylation of IgA1 plays a role in its development. However, the precise role of genetic factors contributing to the abnormal IgA1 galactosylation remains unknown.
In order to examine the effects of C1GALT1 gene encoding core 1 β1,3-galactosyltransferase, an important role in the β1,3 glycosylation of IgA1, on HSPN susceptibility, we conducted a case-control association genetic study in 269 HSP and 61 HSPN in China. Five tagging SNPs, SNP1(-734 C/T), SNP4(-465A/G), SNP6(-330 G/T), SNP7(-292 C/-), and SNP8(1365 G/A) in C1GALT1 were studied using single-locus and haplotype-based multilocus analysis.
Our results demonstrated that 1365 G allele frequency was significantly higher in HSPN patients than in HSP patients without nephritis (0.459 vs 0.331, p = 0.0008, adjusted p' = 0.004) with an odds ratio (OR) = 1.716, 95%CI 1.151-2.560). The GG genotype of 1,365 G/A was significantly different in HSP without nephritis and HSPN (p = 0.008, adjusted p'' = 0.04). We did not observe statistically significant differences in haplotype frequencies between HSPN and HSP patients.
In conclusion, our study suggested that the 1365 G/A polymorphism of the C1GALT1 gene may contribute to HSPN development.
[Show abstract][Hide abstract] ABSTRACT: Henoch-Schönlein purpura (HSP) is considered as an immune-mediated inflammatory disease. Serum amyloid A (SAA) is an acute-phase protein with proinflammatory effects. We investigated the levels of SAA in HSP patients and examined whether SAA levels are associated with organ involvement and disease severity. Seventy patients with HSP, including 35 with nephritis (HSPN) and 35 without HSPN, and 20 controls were recruited in our study. SAA levels were measured and other clinical laboratory parameters, including C-reactive protein, erythrocyte sedimentation rate, complement 3 (C3), C4, and immunoglobulin (Ig) A, were recorded. SAA levels were not found to be independently associated with renal, joint involvement, and disease severity. However, higher SAA levels were observed in HSP patients with gastrointestinal (GI) manifestations (p=0.006, p (c)=0.048). Moreover, the levels of SAA were significantly associated with duration of disease (p<0.005, p(c)<0.04). Our findings suggested that SAA was significantly associated with disease duration and GI manifestations in HSP patients.
[Show abstract][Hide abstract] ABSTRACT: To assess the association of nuclear factor-kappa B (NF-κB) and complications of Kawasaki disease (KD) in Chinese children.
Based on color Doppler examination results, 86 affected children in the KD group were divided into two groups: 39 cases in coronary artery lesion group (CALs subgroup) and 47 cases in non-coronary artery lesion group (Non-CALs subgroup). Infection control group consisted of 65 cases of hospitalized infected children with fever, having same age as the affected children. Healthy control group consisted of 102 cases of healthy children of the same age, visiting the hospital for physical examination. Western blot was used to detect the expression of NF-кBp65 and IкBα proteins in periphery blood mononuclear cells (PBMC); reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of TNF-α and MCP-1 mRNA.
The value of NF-kBp65 (optical density) in the PBMC cell nuclei in the KD group was significantly higher than that in the two control groups (p < 0.01). The value of NF-κBp65 in the CALs subgroup was significantly higher than that in the Non-CALs subgroup (p < 0.05). The value of NF-κBp65 inhibitor IκBα in the KD group was significantly lower than that in the infection control group and the healthy control group (p < 0.01). There was a positive correlation between the ratio nucleus NF-κBP65/ IκBα and the severity degree of CALs(r = 0.536, p < 0.05). The value of TNF-α mRNA (O.D ratio) in the KD group was significantly higher than that in the two control groups (P < 0.01), and the value of TNF-α mRNA in the CALs subgroup was significantly higher than that in the Non-CALs subgroup (P < 0.05). The value of MCP-1 mRNA in the KD group was significantly higher than that in the two control groups (P < 0.01), and the value of MCP-1 mRNA in the CALs subgroup was significantly higher than that in the Non-CALs subgroup (P < 0.05).
NF-κBp65 participates in the pathogenesis of vasculitis of KD in acute stage, and may aggravate the vasculitis in KD and plays a part in the formation of CALs.
The Indian Journal of Pediatrics 06/2011; 78(11):1378-82. DOI:10.1007/s12098-011-0478-x · 0.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Henoch-Schönlein purpura (HSP) is an immune complex-mediated systemic vasculitis. Its genetic etiology remains unknown. CD18, the subunit of integrin beta2 in leukocytes, has essential roles in the expression and function of ITGB2, mediating immune responses. CD18 has been proved to be associated with some systemic vasculitides, such as microscopic polyangiitis and Churg-Strauss syndrome. We aimed to assess the influence of CD18 AvaII polymorphism (rs235326, C->T) in the incidence of HSP and determine its possible implication in severe systemic complications by studying 73 patients with HSP and 156 controls in China. Our results showed that AvaII polymorphism was not associated with HSP susceptibility (odd ratio (OR)=0.48, 95% confidence interval (CI)=0.53-1.39, p=0.63) or with HSP nephritic syndrome (OR=0.88, 95%CI=0.35-2.06, p=0.90). Moreover, we did not observe any significant association between serum parameters, such as CRP, IgA, IgE, C3 and C4, and HSP severity. In conclusion, our results suggested that CD18 AvaII is not associated with HSP susceptibility and its clinical outcomes.
[Show abstract][Hide abstract] ABSTRACT: Henoch-Schönlein purpura (HSP) is a multifactorial inflammatory disease whose pathogenesis remains unknown. Pyrin encoded by the MEFV gene (NM_000243; OMIM 608107) is an important active member of the inflammasome and has been shown to affect the expression of many of the genes involved in immune and inflammatory responses. The aim of our study was to elucidate the possible roles of MEFV genetic variants on the susceptibility to HSP and its clinical outcomes in 78 patients with HSP and 189 controls in China. A significant association was found between the E148Q polymorphism (G->C) and HSP susceptibility (odds ratio 2.76, 95% confidence interval 1.76-4.34, P=0.0001). The C allele of E148Q was associated with joint involvement (P=0.014) but not with HSP nephritis (P=0.1). The clinical score was higher in subjects with the CC genotype than in those with the CG or GG genotype (4.13+/-3.53 vs. 1.94+/-1.70, respectively; P=0.011). P369S was not associated with HSP or other phenotypes. M694V and M680I were absent in our patients. Our results suggest that MEFV E148Q could be a contributory genetic factor to HSP and HSP-related joint syndromes.