Whs Wong

Association of interleukin-10 promoter polymorphisms with systemic lupus erythematosus.

Several lines of evidence suggest interleukin-10 gene (IL-10) is a candidate gene in susceptibility to systemic lupus erythematosus (SLE). We investigated the association of IL-10 promoter single-nucleotide polymorphisms (SNPs) (−3575T/A, −2849G/A, −2763C/A, −1082A/G, −819T/C and −592A/C) and microsatellites (IL10.R, IL10.G) with SLE in 554 Hong Kong Chinese patients and 708 ethnically matched controls. Six haplotypes (hts) were identified from the SNPs. The genotype distribution of the ht1 (T-C-A-T-A), which is associated with low IL-10 production, was different in patients and controls (P=0.009). The homozygous genotype of non-ht1 was significantly increased in patients (P=0.009, odds ratio (OR)=1.80, 95% CI: 1.15–2.82). The frequency of IL10.G4 of IL10.G was also significantly increased in patients (P=0.017, OR=2.53, 95% CI: 1.18–5.40). We found that the homozygous non-ht1 combined with short allele (CA repeat number ⩽21) of IL10.G has a dose-dependent effect on SLE susceptibility: non-ht1/non-ht1 with homozygous short allele showed a higher OR (OR=4.11, 95% CI: 1.27–13.2, P=0.018) of association with SLE than the genotype of non-ht1/non-ht1 with heterozygous short/long allele (OR=2.98, 95% CI: 1.26–7.07, P=0.013) and homozygous long allele (OR=1.05, 95% CI: 0.62–1.78, P=0.848). The frequency of non-ht1 was significantly increased in patients with serositis (P<0.0001, OR=2.42, 95% CI: 1.55–3.80). In conclusion, the high expression promoter genotype is associated with SLE in Chinese.

Necrotizing fasciitis in rheumatic diseases

Necrotizing fasciitis is an uncommon but life-threatening complication in immunocompromised hosts. We reported four patients with rheumatic diseases complicated by necrotizing fasciitis and reviewed 14 others from literature search. Most patients were on corticosteroid treatment. Septic shock, disseminated intravascular coagulopathy and acute renal deterioration were common giving rise to an overall mortality rate of 27.8%. Septic arthritis may also complicate the condition. Statistical analysis on the series showed the lack of major surgical debridement as the only risk factor associated with increased mortality (RR 7.5, 95% CI 2.1-27.3, P = 0.01). Timely debridement of necrotic tissue is important for reducing mortality.

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.

Coronary atherosclerosis using computed tomography coronary angiography in patients with systemic sclerosis

Background: Impaired coronary artery reserve has previously been demonstrated in patients with systemic sclerosis (SSc). Both micro- and macrovascular factors are probably contributory to the underlying pathogenesis. Objectives: To examine the frequency of coronary atherosclerosis in a series of SSc patients by computed tomography coronary angiography (CTCA), a less invasive method than conventional coronary angiography, the current gold standard in the detection of coronary atherosclerosis, and to explore its clinical associations. Methods: Nineteen consecutive SSc patients [six with diffuse (dSSc) and 13 with limited disease (lSSc)] with disease duration of ≥ 3 years were recruited. Coronary calcium score and contrast angiography were examined by CT scan. Conventional cardiovascular factors and inflammatory markers were measured and correlated with CT findings. Results: The mean±SD age of these patients was 52.5±12.5 years with median disease duration of 12.5 years. Six (31.6%) patients were found to have coronary artery calcification (calcium score 13–2008). Coronary calcium was detected in one dSSc patient but contrast angiography was not performed because of interference from an in situ implantable cardiac device. Some parts of the coronary arteries were not assessable in two patients who had ectopic cardiac rhythm. Five lSSc patients had calcified plaques causing variable coronary luminal stenosis. All patients were asymptomatic. Patients with abnormal CTCA findings were more likely to be older (p < 0.001) and were less likely to have serum anti-Scl70 antibodies (p = 0.003) than those without, after Bonferroni correction. Conclusions: Coronary atherosclerosis is not uncommon in asymptomatic SSc patients. CTCA is a convenient and non-invasive method for studying coronary atherosclerosis.