Marco k Kung Ho

Genome-Wide Association Study in Asian Populations Identifies Variants in ETS1 and WDFY4 Associated with Systemic Lupus Erythematosus

Systemic lupus erythematosus is a complex and potentially fatal autoimmune disease, characterized by autoantibody production and multi-organ damage. By a genome-wide association study (320 patients and 1,500 controls) and subsequent replication altogether involving a total of 3,300 Asian SLE patients from Hong Kong, Mainland China, and Thailand, as well as 4,200 ethnically and geographically matched controls, genetic variants in ETS1 and WDFY4 were found to be associated with SLE (ETS1: rs1128334, P = 2.33×10−11, OR = 1.29; WDFY4: rs7097397, P = 8.15×10−12, OR = 1.30). ETS1 encodes for a transcription factor known to be involved in a wide range of immune functions, including Th17 cell development and terminal differentiation of B lymphocytes. SNP rs1128334 is located in the 3′-UTR of ETS1, and allelic expression analysis from peripheral blood mononuclear cells showed significantly lower expression level from the risk allele. WDFY4 is a conserved protein with unknown function, but is predominantly expressed in primary and secondary immune tissues, and rs7097397 in WDFY4 changes an arginine residue to glutamine (R1816Q) in this protein. Our study also confirmed association of the HLA locus, STAT4, TNFSF4, BLK, BANK1, IRF5, and TNFAIP3 with SLE in Asians. These new genetic findings may help us to gain a better understanding of the disease and the functions of the genes involved.

Early clinical predictors of remission of peanut allergy in children

BACKGROUND Understanding predictors of clinical remission would assist in clinical management of peanut allergy. OBJECTIVE We sought to determine the early clinical predictors of peanut allergy remission using a longitudinal cohort of young children with peanut allergy. METHODS Consecutive patients less than 2 years of age with peanut allergy were identified on the basis of skin prick test (SPT) wheal size of 95% positive predictive value or greater. Baseline SPT responses to peanuts, tree nuts, and sesame and serum peanut-specific IgE antibody levels were documented, and follow-up studies were conducted at 1- to 2-year intervals for up to 8 years. Peanut food challenges were performed when SPT responses decreased to less than the 95% positive predictive value for peanut allergy. RESULTS SPT wheal diameters to peanut extract of 6 mm or greater (hazard ratio, 2.16; 95% CI, 1.23-3.786; P = .008) and peanut-specific IgE antibody of 3 kUA/L or greater (hazard ratio, 2.74; 95% CI, 1.13-6.61; P = .025) before the age of 2 years were independent predictors of persistent peanut allergy. Mean SPT wheal diameters of nonremitters increased (r = 0.31, P < .001), whereas those of remitters decreased (r = -0.26, P = .002) between 1 and 4 years of age. Twenty-one percent of young children with peanut allergy became clinically tolerant by age 5 years. CONCLUSIONS Remission of peanut allergy can be predicted by low levels of IgE antibodies to peanut in the first 2 years of life or decreasing levels of IgE sensitization by the age of 3 years.

Mercury Exposure in Children With Autistic Spectrum Disorder: Case-Control Study

Although mercury has been proven to be a neurotoxicant, there is a lack of data to evaluate the causal relationship between mercury and autism. We aim to see if there is increased mercury exposure in children with autistic spectrum disorder. We performed a cross-sectional cohort study over a 5-month period in 2000 to compare the hair and blood mercury levels of children with autistic spectrum disorder (n = 82; mean age 7.2 years) and a control group of normal children (n = 55; mean age 7.8 years). There was no difference in the mean mercury levels. The mean blood mercury levels of the autistic and control groups were 19.53 and 17.68 nmol/L, respectively (P = .15), and the mean hair mercury levels of the autistic and control groups were 2.26 and 2.07 ppm, respectively (P = .79). Thus, the results from our cohort study with similar environmental mercury exposure indicate that there is no causal relationship between mercury as an environmental neurotoxin and autism. (J Child Neurol 2004;19:431-434).

ITGAM is associated with disease susceptibility and renal nephritis of systemic lupus erythematosus in Hong Kong Chinese and Thai

ITGAM was recently found to be associated with systemic lupus erythematosus (SLE) in populations of not only European ancestry, but also in Hispanic- and African-Americans, Mexicans and Colombians. The risk alleles in the gene, however, were found to be monomorphic in two Asian populations examined: Japanese and Korean. In this study, using a collection of 910 SLE patients and 2360 controls from Chinese living in Hong Kong, analyzed by both genome-wide association and direct sequencing, we confirmed the association of the same risk alleles in ITGAM with the disease. These findings were further replicated in the Thai population with 278 patients and 383 ethnicity- and geography-matched controls. Subphenotype stratification analyses showed significantly more involvement of the gene in patients with renal nephritis and neurological disorders. Although our results support a pivotal role by rs1143679 (R77H) in disease association, our data also suggests an additional contribution from rs1143683, another non-synonymous polymorphism in this gene (A858V). Therefore, despite the low-allele frequencies of the risk alleles of the gene in our two Asian populations, ITGAM was confirmed to be a risk factor related to disease susceptibility and probably severe manifestations of SLE.

Increased high sensitivity C reactive protein concentrations and increased arterial stiffness in children with a history of Kawasaki disease

Objectives: To test the hypothesis that low grade inflammation persists after the acute phase and affects arterial stiffness in children with a history of Kawasaki disease. Design and patients: A cohort of 106 children was studied, which comprised 43 patients with Kawasaki disease with coronary aneurysms (group I), 28 patients with Kawasaki disease with normal coronary arteries (group II), and 35 healthy age matched children (group III). Their systemic blood pressure, fasting cholesterol concentrations, serum high sensitivity C reactive protein (hs-CRP) concentrations, and carotid artery stiffness index were compared. Significant determinants of serum hs-CRP concentration and carotid artery stiffness were identified and the relation between hs-CRP concentration and arterial stiffness was investigated. Setting: Tertiary paediatric cardiac centre. Results: Serum hs-CRP concentration of group I patients (median 0.39 mg/l, interquartile range 0.28–0.65 mg/l) was significantly greater than that of group II (median 0.24 mg/l, interquartile range 0.17–0.29 mg/l, p < 0.001) and of group III patients (median 0.25 mg/l, interquartile range 0.18–0.40 mg/l, p < 0.01). Likewise, carotid artery stiffness index of group I patients (mean (SD) 5.07 (1.11)) was significantly greater than that of group II (4.27 (0.83), p  =  0.002), and of group III patients (4.24 (0.86), p  =  0.001). For the entire cohort, the carotid artery stiffness index correlated positively with log serum hs-CRP concentration (r  =  0.24, p  =  0.013). In multiple linear regression analysis, age (standardised β  =  0.22, p  =  0.02), systolic blood pressure (standardised β  =  0.28, p  =  0.01), log serum hs-CRP concentration (standardised β  =  0.21, p  =  0.017), and patient grouping (standardised β  =  −0.36, p < 0.001) were all independently associated with the carotid artery stiffness index. Conclusions: These findings support the possibility of ongoing low grade inflammation late after the acute phase of Kawasaki disease in patients with coronary aneurysms. Furthermore, this low grade inflammation may have a role in increasing systemic arterial stiffness.

The prevalence of food allergy in infants in Chongqing, China

To cite this article: Chen J, Hu Y, Allen KJ., Ho MHK, Li H. The prevalence of food allergy in infants in Chongqing, China. Pediatric Allergy Immunology 2011; 22: 356–360.

ELF1 is associated with systemic lupus erythematosus in Asian populations

Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong genetic involvement. The susceptibility genes identified so far can only explain a small proportion of disease heritability. Through a genome-wide association in a Hong Kong Chinese cohort and subsequent replication in two other Asian populations, with a total of 3164 patients and 4482 matched controls, we identified association of ELF1 (E74-like factor 1) with SLE (rs7329174, OR = 1.26, joint P= 1.47 × 10(-8)). ELF1 belongs to the ETS family of transcription factors and is known to be involved in T cell development and function. Database analysis revealed transcripts making use of three alternative exon1s for this gene. Near equivalent expression levels of distinct transcripts initiated from alternative exon1s were detected in peripheral blood mononuclear cells from both SLE patients and healthy controls. Although a direct association of rs7329174 with the three forms of transcripts for this gene was not detected, these findings support an important role of ELF1 in SLE susceptibility and suggest a potentially tight regulation for the expression of this gene.

Scientific basis of botanical medicine as alternative remedies for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disorder that causes permanent disability and mortality to approximately 1 to 100 people in the world. Patients with RA not only suffer from pain, stiffness, swelling, and loss of function in their joints, but also have a higher risk of cardiovascular disease and lymphoma. Typically prescribed medications, including pain-relieving drugs, nonsteroidal anti-inflammatory drugs (NSAID), and disease-modifying antirheumatic drugs, can help to relieve pain, reduce inflammation and slow the course of disease progression in RA patients. However, the general effectiveness of the drugs has been far from satisfactory. Other therapeutic modalities like TNF-alpha (TNF-α) inhibitors and interleukin-1 receptor antagonists targeting precise pathways within the immune system are expensive and may be associated with serious side effects. Recently, botanical medicines have become popular as alternative remedies as they are believed to be efficacious, safe and have over a thousand years experience in treating patients. In this review, we will summarize recent evidence for pharmacological effects of herbs including Black cohosh, Angelica sinensis, Licorice, Tripterygium wilfordii, Centella asiatica, and Urtica dioica. Scientific research has demonstrated that these herbs have strong anti-inflammatory and anti-arthritic effects. A wide range of phytochemicals including phenolic acids, phenylpropanoid ester, triterpene glycosides, phthalide, flavonoids, triterpenoid saponin, diterpene and triterpene have been isolated and demonstrated to be responsible for the biological effects of the herbs. Understanding the mechanisms of action of the herbs may provide new treatment opportunities for RA patients.

Clinical Characteristics and Genotype-phenotype Correlation in 62 Patients with X-linked Agammaglobulinemia

IntroductionX-linked agammagobulinemia (XLA) is a primary immunodeficiency disorder caused by Brutons tyrosine kinase (Btk) gene mutation. Recent studies suggested genotype-phenotype correlation in XLA, but a definitive association remains controversial.Patients and MethodsWe examined the relationship between specific Btk gene mutations and severity of clinical presentation in 62 patients with XLA. Disease severity was assessed by the age of disease onset and the presence of severe infections, while mutations were classified into severe and mild based on structural and functional consequence by bioinformatics analysis.ResultsFifty-six Btk mutations were identified in 62 patients from 57 kindreds. Variation in phenotypes was observed, and there was a tendency of association between genotype and age of disease onset as well as occurrence of severe infections.ConclusionA critical analysis of the circumstances upon presentation also revealed that under-recognition of recurrent infections and relevant family history are important hurdles to timely diagnosis of XLA.

Environmental mercury exposure in children: South China's experience

Background : Environmental mercury levels significantly increased in the past decades following its increase in industrial applications. In spite of an increasing concern on the potential harmful effects of mercury on children, there is no reported data for the Chinese population. The relationship between dietary habit and environmental mercury exposure in Chinese children was studied.