Brief Report: Influence of HLA-DRB1 Susceptibility Alleles on the Clinical Subphenotypes of Systemic Lupus Erythematosus in Koreans.

OBJECTIVE: To investigate the association between HLA-DRB1 alleles and systemic lupus erythematosus (SLE) susceptibility and features of SLE, such as clinical manifestations and autoantibody profiles, in a Korean population. METHODS: We tested the genetic associations between HLA-DRB1 alleles and SLE susceptibility and clinical subphenotypes in 1,089 patients with SLE and 2,161 control subjects, including a discovery set (475 patients and 1,119 controls) and a replication set (614 patients and 1,042 controls). We used a relative predispositional effects (RPEs) method to examine the independent effect of each allele associated with SLE or its subphenotypes. RESULTS: We identified 4 HLA-DRB1 alleles that were associated with increased susceptibility to SLE, 2 of which had been detected previously (*15:01; P for RPE = 1.11 × 10(-13) , odds ratio [OR] 1.88) and *09:01 (P for RPE = 1.59 × 10(-5) , OR 1.46), and 2 of which were novel alleles (*08:03 [P for RPE = 8.80 × 10(-8) , OR 1.62]) and *07:01 (P for RPE = 1.14 × 10(-6) , OR 1.57)]. In addition, protective effects on the development of SLE were observed for 2 novel alleles (HLA-DRB1*12:02 [P for RPE = 6.35 × 10(-4) , OR 0.49]) and *11:01 [P for RPE = 1.24 × 10(-3) , OR 0.59]). The SLE risk alleles had an additive genetic effect, as demonstrated by the finding that double copies of these alleles (OR 3.38) had larger risk effects size compared with single copies (OR 1.95) and no copy (OR 1 [reference]). In a subphenotype analysis, various HLA-DRB1 alleles (including SLE risk alleles) were observed to have significant predispositional effects on diverse clinical manifestations. In particular, HLA-DRB1*15:01 (OR 2.30), *09:01 (OR 2.46), *07:01 (OR 2.61), and *08:03 (OR 2.97) were strongly associated with the risk of anti-Sm antibody production. CONCLUSION: We detected 6 HLA-DRB1 alleles that were associated with SLE in Koreans. The SLE risk alleles promoted the production of autoantibodies, including anti-Sm, and diverse clinical manifestations.

Impact of low-dose aspirin on coronary artery spasm as assessed by intracoronary acetylcholine provocation test in Korean patients.

High-dose aspirin has been reported to aggravate coronary artery spasm (CAS). However, it is unknown whether low-dose aspirin (LDA; 100 mg) has deleterious impact on CAS. We assessed the impact of LDA on CAS induced by intracoronary acetylcholine (ACh) provocation test. A total of 2789 consecutive patients without significant coronary artery disease who underwent ACh test between November 2004 and March 2010 were enrolled. The patients were divided into two groups: the aspirin group taking LDA before ACh test (n=221) and the no aspirin group not taking aspirin (n=2568). At baseline, the prevalence of old age, diabetes mellitus, hypertension, and hyperlipidemia were higher in the aspirin group. During the ACh test, the incidence of significant CAS, ischemic chest pain, as well as severe and multivessel spasm was higher in the aspirin group. The response rate to lower ACh dose was higher in the aspirin group. Multivariate analysis showed that the previous use of LDA was an independent predictor of CAS (adjusted odds ratio, 1.6, 95% confidence interval, 1.0-2.3; p=0.031). However, it is likely that the association of LDA and CAS that we have observed is not causal but may be hypothesis generating due to significant baseline differences. Further, male gender, old age, lipid-lowering drugs, baseline spasm, and myocardial bridge were independent predictors of CAS. LDA was more frequently associated with CAS and ischemic symptoms, as well as severe and multivessel spasm, suggesting the patients who have received LDA would require more intensive medical therapies and close follow up.

Etanercept treatment in rheumatoid arthritis patients with chronic kidney failure on predialysis.

Rheumatoid arthritis (RA) patients with chronic kidney failure are intolerant to most disease-modifying antirheumatic drugs (DMARDs) and NSAIDs due to their potential toxicities. Although the tumor necrosis factor (TNF) inhibitors have emerged as a highly effective treatment for RA, their safety and efficacy in RA patients with chronic kidney failure have not been well reported. We retrospectively evaluated the safety and efficacy of etanercept treatment in RA patients with chronic kidney failure. We describe three RA patients with chronic kidney failure who had been treated with DMARDs, steroids and NSAIDs, but were discontinued from these classical agents due to several side effects and nephrotoxicity. The patients were treated with 25 mg of etanercept once or twice a week. We evaluated disease activity and used decreasing renal function and increasing number of infections to monitor safety. All three patients improved after starting etanercept treatment and their steroid requirements were decreased. Linear relationships between Modification of Diet in Renal Disease study equation (MDRD) glomerular filtration rate (GFR) and time were observed. Thus, in all patients, the changes in GFR did not represent superimposed acute drug toxicity, but rather chronic progressive renal failure. These cases show that etanercept may be a safe and effective treatment option for RA patients with chronic kidney failure.