Kw Lee

Population differences in SLE susceptibility genes: STAT4 and BLK, but not PXK, are associated with systemic lupus erythematosus in Hong Kong Chinese.

In this study, we compared the association of several newly discovered susceptibility genes for systemic lupus erythematosus (SLE) between populations of European origin and two Asian populations. Using 910 SLE patients and 1440 healthy controls from Chinese living in Hong Kong, and 278 SLE patients and 383 controls in Thailand, we studied association of STAT4, BLK and PXK with the disease. Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 × 10−23) and BLK (rs13277113, OR=0.77, P=1.34 × 10−5) with SLE. It was showed that rs7574865 of STAT4 is also linked to hematologic disorders and potentially some other subphenotypes of the disease. More than one genetic variant in STAT4 were found to be associated with the disease independently in our populations (rs7601754, OR=0.59, P=1.39 × 10−9, and P=0.00034 when controlling the effect of rs7574865). With the same set of samples, however, our study did not detect any significant disease association for PXK, a risk factor for populations of European origin (rs6445975, joint P=0.36, OR=1.06, 95% confidence interval: 0.93–1.21). Our study indicates that some of the susceptibility genes for this disease may be population specific.

Association of BANK1 and TNFSF4 with systemic lupus erythematosus in Hong Kong Chinese

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. Recently, single nucleotide polymorphisms (SNPs) in BANK1 and TNFSF4 have been shown to be associated with SLE in Caucasian populations, but it is not known whether they are also involved in the disease in other ethnic groups. Recent data from our genome-wide association study (GWAS) for 314 SLE cases and 920 controls collected in Hong Kong identified SNPs in and around BANK1 and TNFSF4 to be associated with SLE risk. On the basis of the results of the reported studies and our GWAS, SNPs were selected for further genotyping in 949 SLE patients (overlapping with the 314 cases in our GWAS) and non-overlapping 1042 healthy controls. We confirmed the associations of BANK1 and TNFSF4 with SLE in Chinese (BANK1, rs3733197, odds ratio (OR)=0.84, P=0.021; BANK1, rs17266594, OR=0.61, P=4.67 × 10−9; TNFSF4, rs844648, OR=1.22, P=2.47 × 10−3; TNFSF4, rs2205960, OR=1.30, P=2.41 × 10−4). Another SNP located in intron 1 of BANK1, rs4522865, was separately replicated by Sequenom in 360 cases and 360 controls and was also confirmed to be associated with SLE (OR=0.725, P=2.93 × 10−3). Logistic regression analysis showed that rs3733197 (A383T in ankyrin domain) and rs17266594 (a branch point-site SNP) from BANK1 had independent contributions towards the disease association (P=0.037 and 6.63 × 10−8, respectively). In TNFSF4, rs2205960 was associated with SLE independently from the effect of rs844648 (P=6.26 × 10−3), but not vice versa (P=0.55). These findings suggest that multiple independent genetic variants may be present within the gene locus, which exert their effects on SLE pathogenesis through different mechanisms.

Safety of Hormonal Replacement Therapy in Postmenopausal Patients with Systemic Lupus Erythematosus

It remains controversial whether administration of exogenous estrogens is safe in systemic lupus erythematosus (SLE). The current study was undertaken to determine the effect of hormone replacement therapy (HRT) on the rate and magnitude of flares in a cohort of postmenopausal SLE patients. Thirty-four patients were prospectively followed. The frequency and severity of disease exacerbations in 11 patients who received HRT was compared with 23 patients who did not receive HRT. Our results showed that both users and non-users of HRT had a comparable age of disease onset, duration of disease, clinical manifestations, and duration of follow-up. No significant increase in the rate (0.12 relapses/patient-year in HRT group vs 0.16 relapses/patient-year in the non-HRT group, p = 0.90) or magnitude (total SLEDAI score increase during flares/patient-year in the HRT and non-HRT groups were 0.55 and 1.22, respectively, p = 0.57) of flares could be demonstrated in patients who received HRT over a median follow-up period of 35 months. We concluded that HRT appeared to be well tolerated and safe in postmenopausal SLE patients. Its potential beneficial effect may outweigh its deleterious effect on disease activity.

Evaluating different imaging strategies in children after first febrile urinary tract infection

We conducted a retrospective multicenter review to estimate the prevalence of urological abnormalities in Chinese children with first febrile urinary tract infection (UTI) and to evaluate the selective imaging strategy recommended by the NICE guideline for detecting underlying abnormalities. Atypical UTI was defined as in the NICE UTI guideline. Overall, 576 boys and 244 girls aged below 24 months were reviewed. All underwent ultrasound (US) and micturating cystourethrogram (MCUG) and 612 underwent DMSA scans. US was abnormal in 73 (8.9%) and vesicoureteral reflux was shown in 195 patients (23.8%). A total of 126 patients were considered to have remediable urological abnormalities requiring additional surgical or medical interventions. The NICE guideline yielded excellent negative predictive values (NPV) of 100–94.4% in girls but 91% in boys. If all boys underwent US and DMSA and only those with atypical UTI or abnormal US or DMSA proceeded to MCUG, then the NPV increased to 95.2% and 97.4% for boys aged below and above 6 months, respectively. These revised strategies would substantially save invasive studies—DMSA and MCUG in 27 and 74% of girls aged below and above 6 months, respectively, or MCUG in 23 and 59% of boys aged below and above 6 months, respectively.

Association of CD247 with systemic lupus erythematosus in Asian populations

Objective: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. CD247 (CD3Z, TCRZ) plays a vital role in antigen recognition and signal transduction in antigen-specific immune responses, and is known to be involved in SLE pathogenesis. Weak disease association was reported for genetic variants in this gene in Caucasian studies for SLE, Crohns disease and systemic sclerosis, but its role as a genetic risk factor was never firmly established. Methods: In this study, using a collection of 612 SLE patients and 2193 controls of Chinese ethnicity living in Hong Kong in a genome-wide study, single nucleotide polymorphisms (SNPs) in and around CD247 were identified as being associated with SLE. The two most significant SNPs in this locus were selected for further replication using TaqMan genotyping assay in 3339 Asian patients from Hong Kong, Mainland China, and Thailand, as well as 4737 ethnically and geographically matched controls. Results: The association of CD247 with SLE in Asian populations was confirmed (rs704853: odds ratio [OR] = 0. 81, p = 2.47 × 10−7; rs858543: OR = 1.10, p = 0.0048). Patient-only analysis suggested that rs704853 is also linked to oral ulcers, hematologic disorders and anti-double-stranded DNA (dsDNA) antibody production. Conclusion: A significant association between variants in CD247 and SLE was demonstrated in Asian populations. Understanding the involvement of CD247 in SLE may shed new light on disease mechanisms and development of new treatment paradigms.

Oscillometric 24-h ambulatory blood pressure reference values in Hong Kong Chinese children and adolescents

Objectives: We aimed to establish community-based normal reference values of 24-h ambulatory blood pressure monitoring (ABPM) for Chinese children and adolescents. Furthermore, we investigated how excluding overweight children affects BP percentiles and compared them with German references. Methods: In this territory-wide cross-sectional prospective cohort study, 1445 Hong Kong Chinese children and adolescents aged 8–17 years with body height between 119 and 185 cm were recruited. Their ABPM assessment was performed using validated arm oscillometric recorders (A&D TM-2430) and complied with American Heart Associations recommendations. The reference tables were constructed using the LMS method to normalize skewed distribution of ABP data to sex and age or height. Results: The ambulatory BP was higher among boys and the difference between boys and girls progressively widened with age. An increasing trend in daytime and night-time SBP and DBP with age and height was observed in both sexes. The age-specific and sex-specific 95th percentiles from nonoverweight children (n = 1147; 79%) were lower than the whole cohort by up to 2.5 and 1 mmHg for SBP and DBP, respectively. In comparison, our overall and nonoverweight reference standards were generally higher than corresponding German references. Conclusion: The study provides ambulatory BP standards for Chinese children, with sex-related age-specific and height-specific percentiles. Further longitudinal studies are required for investigating its clinical utility in Chinese.

Clinical course and outcome of steroid sensitive nephrotic syndrome in children: a single center experience

Abstract It is difficult at present to predict the long-term course of steroid sensitive nephrotic syndrome (SSNS) regarding the probability of relapse. We retrospectively reviewed 42 SSNS patients who had been followed up for a mean duration of 10 ±3 years. Male was predominantly affected (M:F = 3.5:1). Sixty percent of our children presented between 2 to 5 years old. At the time of last follow- up, seven patients (17%) never had a relapse. Twenty-three patients (55%) went into long-term remission and 12 (28%) continued to have active disease. Kidney biopsies were performed in 18 patients (43%). The most common histology was minimal change disease (71%), followed by IgM nephropathy (28%). Thirty-four patients (81%) followed the steroid treatment protocol of the International Study of Kidney Disease in Childhood (ISKDC). Sixteen patients (38%) required second line medications. The most common steroid sparing agents used were levamisole, followed by cyclophosphamide and cyclosporin A. The nonrelapsers had a higher serum albumin than the relapsers, with a p value of 0.03. From the second year of follow-up onwards, the long-term remission group had fewer episodes of relapses than the active disease group, with a p value of ≤ 0.034 at the second subsequent years. The median time to achieve the long-term remission is 3 years (95% confidence interval: 1.85-4.15) in our patients. Among all the prognostic factors studied, a higher serum albumin at presentation and a fewer number of relapses per year appeared to be related to a less relapsing course.