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

Intrathecal immunoglobulin production in patients with systemic lupus erythematosus with neuropsychiatric manifestations [9]

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Pregnancy outcome in patients with adult onset Still's disease

Pregnancy outcome of patients with adult onset Still's disease (AOSD) has not been addressed. We report the maternal and fetal morbidity of 5 pregnancies from 3 Chinese patients with AOSD and review another 17 pregnancies from 14 patients reported in the English literature. Nine patients had their first manifestation in the 5th to 6th gestational month. Disease relapse in patients with known AOSD occurred most commonly in the post-partum period. Most did not respond satisfactorily to nonsteroidal antiinflammatory agents alone, but responded to administration of corticosteroids, especially in high doses.link_to_subscribed_fulltex

Tuberculosis in systemic lupus erythematosus in an endemic area and the role of isoniazid prophylaxis during corticosteroid therapy

Objective. The efficacy of isoniazid (INAH) prophylaxis against tuberculosis (TB) in patients taking corticosteroid remains controversial. Hong Kong is an endemic area for TB, with an annual risk of 0.11/100 in the general population. Patients with systemic lupus erythematosus (SLE) have an increased susceptibility to TB because of their intrinsic immunocompromised state and the use of corticosteroid therapy. We examined the usefulness of INAH in the prevention of recurrences of TB in patients with SLE receiving high dose corticosteroid therapy. Methods. Medical records of a cohort of patients with SLE were reviewed. Patients with a history of TB who had previously been adequately treated were retrospectively examined for subsequent recurrence of TB. A comparison was performed based on the use of INAH at the discretion of the attending physician in some patients (INAH group) but not others (non-INAH group) during lupus exacerbation that required the use of prednisolone ≥ 15 mg/day or equivalent. Results. A total of 91 episodes of TB from 76 individuals in a cohort of 652 SLE patients with a duration of followup of 13.9 ± 7.5 years were identified (prevalence of 1.06/100 patient-years). 43 episodes were given INAH while 48 were not. There were 18 recurrences of TB (recurrence rate of 1.66/100 patient-years). Recurrence rates in the INAH and non-INAH groups were 1.59 and 1.74 per 100 patient-years (p = 0.72). However, patients in the INAH group had more lupus exacerbations. Further, extrapulmonary TB was also found to have a higher recurrence rate than pulmonary TB. A case-controlled analysis was thus performed (n = 46) matching patients for the number of lupus exacerbations, cumulative doses of prednisolone, and initial site of TB. There was no difference in the recurrence rates of TB between the matched INAH (0.55/100 patient-years) and non-INAH (1.04/100 patient-years) groups (p = 0.66). Conclusion. Patients with SLE have a higher prevalence of TB infection than the general population. They are at risk of TB recurrence when given immunosuppressive doses of corticosteroid.link_to_subscribed_fulltex

Antiphospholipid antibody profiles and their clinical associations in Chinese patients with systemic lupus erythematosus

Objective. Different prevalences of antiphospholipid antibodies (aPL) have been reported in different populations of patients with systemic lupus erythematosus (SLE). Chinese are generally believed to have lower risk of vascular thrombosis. We examined the prevalence of aPL including lupus anticoagulant (LAC), anticardiolipin (aCL) and anti-β 2- glycoprotein I (anti-β 2-GPI) antibodies, the level of thrombotic risk, and the association of aPL with thrombotic and pregnancy outcomes in a Chinese cohort with SLE at the university lupus clinic during the period 1986-2003. Methods. aPL were measured in 272 SLE patients, and medical records were reviewed for vascular thrombosis and pregnancy outcomes. Results. The prevalence of LAC, IgG aCL, and IgG anti-β 2-GPI antibodies was 22.4%, 29.0%, and 7.7%, respectively. There were 38 episodes of thrombosis after a mean duration of followup of 11.0 ± 6.8 SD years, giving a thrombotic rate of 1.26/100 patient-years. All aPL were shown to be associated with vascular thrombosis. IgG anti-β 2-GPI antibodies were found to be associated with recurrent thrombosis [8.0/100 patient-years or 25.0% (7/28)]. Patients taking hydroxychloroquine were found to have fewer thrombotic complications than those who were not (OR 0.17, 95% CI 0.07-0.44; p < 0.0001). LAC was the strongest factor associated with recurrent miscarriages [relative risk 12.3, 95% CI 1.22-123.31; p = 0.03). The diagnosis of secondary antiphospholipid syndrome was satisfied in 8.9% of patients. Conclusion. The lifetime and recurrent thrombotic rates in our patients with aPL were not particularly different from those in the literature. However, the lower prevalence of aPL in our cohort may suggest a role of other prothrombotic factors in predisposition to thrombosis.link_to_subscribed_fulltex

Antiphospholipid antibody profiles and their clinical associations in Chinese patients with systemic lupus erythematosus

Objective. Different prevalences of antiphospholipid antibodies (aPL) have been reported in different populations of patients with systemic lupus erythematosus (SLE). Chinese are generally believed to have lower risk of vascular thrombosis. We examined the prevalence of aPL including lupus anticoagulant (LAC), anticardiolipin (aCL) and anti-β 2- glycoprotein I (anti-β 2-GPI) antibodies, the level of thrombotic risk, and the association of aPL with thrombotic and pregnancy outcomes in a Chinese cohort with SLE at the university lupus clinic during the period 1986-2003. Methods. aPL were measured in 272 SLE patients, and medical records were reviewed for vascular thrombosis and pregnancy outcomes. Results. The prevalence of LAC, IgG aCL, and IgG anti-β 2-GPI antibodies was 22.4%, 29.0%, and 7.7%, respectively. There were 38 episodes of thrombosis after a mean duration of followup of 11.0 ± 6.8 SD years, giving a thrombotic rate of 1.26/100 patient-years. All aPL were shown to be associated with vascular thrombosis. IgG anti-β 2-GPI antibodies were found to be associated with recurrent thrombosis [8.0/100 patient-years or 25.0% (7/28)]. Patients taking hydroxychloroquine were found to have fewer thrombotic complications than those who were not (OR 0.17, 95% CI 0.07-0.44; p < 0.0001). LAC was the strongest factor associated with recurrent miscarriages [relative risk 12.3, 95% CI 1.22-123.31; p = 0.03). The diagnosis of secondary antiphospholipid syndrome was satisfied in 8.9% of patients. Conclusion. The lifetime and recurrent thrombotic rates in our patients with aPL were not particularly different from those in the literature. However, the lower prevalence of aPL in our cohort may suggest a role of other prothrombotic factors in predisposition to thrombosis.link_to_subscribed_fulltex