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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.

Objective. To compare the incidence and risk factors for thromboembolic events in systemic lupus erythematosus (SLE) patients of different ethnic backgrounds.Methods. SLE patients who were newly diagnosed or were referred within 6 months of diagnosis between 1996 and 2002 were prospectively followed up for the occurrence of thromboembolic events. Cumulative hazard and risk factors for thromboembolism were evaluated and compared among patients of different ethnic origins.Results. We studied 625 patients who fulfilled the American College of Rheumatology criteria for SLE (89% women): 258 Chinese, 140 African Americans, and 227 Caucasians. The mean ؎ SD age at SLE diagnosis was 35.7 ؎ 14 years. After a followup of 3,094 patientyears, 48 arterial events and 40 venous events occurred in 83 patients. The overall incidence of arterial and venous thromboembolism was 16/1,000 patient-years and 13/1,000 patient-years, respectively. The cumulative hazard of arterial events at 60 months after the diagnosis of SLE was 8.5%, 8.1%, and 5.1% for the Chinese, African Americans, and Caucasians, respectively. The corresponding cumulative risk of venous events was 3.7%, 6.6%, and 10.3%, respectively (P ‫؍‬ 0.008 for Chinese versus Caucasians, by log rank test). Smoking, obesity, antiphospholipid antibodies, and use of antimalarial agents and exogenous estrogens were less frequent in the Chinese patients. In Cox regression models, low levels of high-density lipoprotein (HDL) cholesterol, Chinese ethnicity, oral ulcers, and serositis predicted arterial events, whereas male sex, low levels of HDL cholesterol, antiphospholipid antibodies, non-Chinese ethnicity, obesity, renal disease, and hemolytic anemia predicted venous events.Conclusion. There are ethnic differences in the incidence of arterial and venous thromboembolism in patients with SLE that cannot be fully explained by the clinical factors studied. Further evaluation of other genetic and immunologic factors is warranted.Premature atherosclerosis is a major cause of mortality and late morbidity in patients with systemic lupus erythematosus (SLE) (1-3). In several cohort studies, it was found that atherosclerotic cardiovascular and cerebrovascular diseases are more common causes of late deaths than active SLE itself (1,(4)(5)(6). More recent studies have demonstrated that subclinical coronary heart disease and carotid plaque were present in a significantly higher proportion of SLE patients than in age-and sex-matched control subjects with similar risk factors (7,8). The etiology of accelerated atherosclerosis in SLE is multifactorial and cannot be fully explained by traditional risk factors (9).Compared with individuals without SLE, the risk of myocardial infarction in SLE patients is 2-50 times higher, and the risk of stroke is 2-10 times higher (2,9,10). The prevalence of symptomatic coronary heart disease in SLE patients has been reported to be 6-20%, The Hopkins Lupus Cohort is supported by NIH grants R01-AR-43727 and M01-RR-00052 (to the outpatient Clinical Research Center).

Objective. To evaluate the prevalence of the metabolic syndrome in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA). Methods. Consecutive patients with RA, AS, or PsA who attended our outpatient arthritis clinics between July and November 2009 were recruited for a study of atherosclerotic risk factors and the metabolic syndrome, defined according to the 2009 joint statements using the Asian criteria for central obesity. Results. Nine hundred thirty patients were studied (699 with RA, 122 with AS, and 109 with PsA; 70% women, mean ؎ SD age 51.1 ؎ 12.7 years). The mean ؎ SD disease duration for patients with RA, AS, and PsA was 5.3 ؎ 5.4, 6.0 ؎ 5.6, and 3.6 ؎ 3.1 years, respectively. The prevalence of metabolic syndrome was significantly higher in PsA (38%) than RA (20%) or AS (11%; P < 0.001). The odds ratios (ORs) for the metabolic syndrome compared to age-and sex-matched controls were 0.98 (95% confidence interval [95% CI] 0.78 -1.23, P ‫؍‬ 0.88), 0.59 (95% CI 0.30 -1.15, P ‫؍‬ 0.12), and 2.68 (95% CI 1.60 -4.50, P < 0.001), respectively, for RA, AS, and PsA. Patients with PsA had a significantly higher prevalence of impaired fasting glucose (30%; P < 0.001), low high-density lipoprotein (HDL) cholesterol (33%; P < 0.001), high triglycerides level (21%; P ‫؍‬ 0.008), central obesity (65%; P < 0.001), and high blood pressure (56%; P ‫؍‬ 0.045). In a logistic regression model, the adjusted OR for the metabolic syndrome in PsA was 2.44 (95% CI 1.48 -4.01, P < 0.001) relative to RA or AS. The adjusted ORs for central obesity, impaired fasting glucose, hypertriglyceridemia, and low HDL cholesterol were also significantly higher in PsA patients. Conclusion. Patients with PsA, but not RA or AS, have a significantly higher prevalence of the metabolic syndrome compared to the general population. Among the 3 diseases studied, PsA has the highest prevalence of the metabolic syndrome and is associated with the highest cardiovascular risk.

Objective. To study the genetic association of interleukin-10 (IL-10) promoter polymorphisms in Southern Chinese patients with systemic lupus erythematosus (SLE), and to investigate possible associations with clinical manifestations of the disease.Methods. DNA was extracted from 88 Chinese patients with SLE and 83 ethnically matched controls. The IL-10 promoter region between positions -533 and -1120 was amplified by polymerase chain reaction, and polymorphisms were detected by restriction-enzyme cleavage.Results. No significant difference in the allele or haplotype frequencies between SLE patients and controls could be demonstrated. The *A and aC alleles at the -597 position were linked to the *T and *C alleles at the -824 position, respectively. However, when clinical features were examined, the *A allele at the -597 position and the *T allele at the -824 position were significantly associated with lupus nephritis, by chisquare analysis ( 2 ' < 0.001, odds ratio 4.19, 95% confidence interval 2.02-8.71). Similarly, the haplotype -1087*A/-824*T/-597*A was also associated with renal involvement (P < 0.001, odds ratio 3.62, 95%confidence interval 1.80-7.31).Conchsion. IL-10 promoter polymorphisms are not strong determinants of susceptibility to the development of SLE, per se, in Southern Chinese individuals. However, IL-10 genotypes are strongly associated with certain clinical manifestations of SLE and may have a role in predicting disease prognosis.

The aims were to study the gender differences in clinical manifestations, disease course and organ damage in systemic lupus erythematosus (SLE). Clinical manifestations, autoantibody profile, relapses and damage scores were obtained from 51 Chinese males with SLE and compared with 201 consecutive female SLE controls. Fifty-one males were identified among 630 SLE patients who attended our clinics, giving a male prevalence of 8% and a female to male ratio of 11.4-1. Both the male SLE patients and the female controls had similar age and SLEDAI score at disease onset. Male SLE patients had less alopecia (P = 0.03), Raynaud's phenomenon (P = 0.01) and anti-Ro (P = 0.049) during the course of the disease but none of the differences were statistically significant after correction for multiple observations. The prevalence of major organ involvement in either sex was not different. Both groups of patients had a comparable mean duration of follow-up (104 vs. 102 months, P = 0.87). Males had a significantly lower rate of relapses (total No. of flares/patient-year: 0.23 in men vs. 0.33 in women, P = 0.04), but the frequency of severe flares (No. of severe flares/patient-year in men 0.08 vs. 0.12 in women, P = 0.16) was not significantly different from the females. Male patients with positive anti-Ro had significantly less overall flares than their female counterparts who were anti-Ro positive (0.16 vs. 0.34, P = 0.006). However, the use of immunosuppressive agents for disease control in patients of both sexes was similar. 22 (43%) of the males and 78 (39%) of the females had organ damage. A higher percentage of male patients had impairment of renal function (P = 0.006) but the proportion of patients who required dialysis was not different (4% in men vs. 2% in females. P = 0.92). There was also a trend of more cardiovascular damage in the males but the difference was not statistically significant (P = 0.09). The mean SLICC/ACR scores were not significantly higher in the males than the females (0.71 vs. 0.60, P = 0.47). Males tend to differ from females in clinical manifestations, immunological profile and disease course in SLE. However, there was no gender difference in the involvement of major organs/systems. Males had less overall disease flares than the females but the rate of severe flares was not significantly lower. For patients who were anti-Ro positive, males had significantly less total number of flares/patient-year than their female counterparts. More renal impairment and cardiovascular damage was present in our male lupus patients but the overall damage scores were not significantly higher.

The survival of SLE in our southern Chinese patients is similar to that of the Caucasian series reported in the 1990s. Although nephritis contributes to organ damage, it is not a major determinant for survival. Infection remains the commonest cause of death. High-dose steroid treatment and thrombocytopenia are independent risk factors for mortality. Judicious use of immunosuppressive agents is necessary to improve the short-term survival of SLE.