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Systemic lupus erythematosus (SLE) has a strong but incompletely understood genetic architecture. We conducted an association study with replication in 4,492 SLE cases and 12,675 controls from six East-Asian cohorts, to identify novel and better localize known SLE susceptibility loci. We identified 10 novel loci as well as 20 known loci with genome-wide significance. Among the novel loci, the most significant was GTF2IRD1-GTF2I at 7q11.23 (rs73366469, Pmeta=3.75×10−117, OR=2.38), followed by DEF6, IL12B, TCF7, TERT, CD226, PCNXL3, RASGRP1, SYNGR1 and SIGLEC6. We localized the most likely functional variants for each locus by analyzing epigenetic marks and gene regulation data. Ten putative variants are known to alter cis- or trans-gene expression. Enrichment analysis highlights the importance of these loci in B- and T-cell biology. Together with previously known loci, the explained heritability of SLE increases to 24%. Novel loci share functional and ontological characteristics with previously reported loci, and are possible drug targets for SLE therapeutics.

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse manifestations, and its pathogenesis is unclear and complicated. Infection and SLE are similar in that they both cause inf lammatory reactions in the immune system; however, one functions to protect the body, whereas the other is activated to damage the body. Infection is known as one of the common trigger factors for SLE; there are a number of reports on infectious agents that provoke autoimmune response. Several viruses, bacteria, and protozoa were revealed to cause immune dysfunction by molecular mimicry, epitope spreading, and bystander activation. In contrast, certain pathogens were revealed to protect from immune dysregulation. Infection can be threatening to patients with SLE who have a compromised immune system, and it is regarded as one of the common causes of mortality in SLE. A clinical distinction between infection and lupus f lare up is required when patients with SLE present fevers. With a close-up assessment of symptoms and physical examination, C-reactive protein and disease activity markers play a major role in differentiating the different disease conditions. Vaccination is necessary because protection against infection is important in patients with SLE.

Vitamin D is a pleiotrophic hormone with immunoregulatory properties. Low levels of vitamin D have been discovered in various autoimmune diseases. Here, we investigated serum vitamin D levels in Koreans with systemic lupus erythematosus (SLE) and examined whether levels correlate with disease activity of SLE. Blood samples were prospectively collected from patients with SLE (n = 104) and normal controls (NC, n = 49) during the spring from March to May 2008. The level of serum 25-hydroxyvitamin D (25(OH)D3) was measured by radioimmunoassay. The serum 25(OH)D3 levels of patients with SLE (42.49 ± 15.08 ng/ml) were significantly lower than NC (52.72 ± 15.19 ng/ml, P \ 0.001). Additionally, 17 patients with SLE (16.3%) had vitamin D insufficiency, while two NC had vitamin D insufficiency (4.1%). The risk of vitamin D insufficiency was 4.6-fold increased in SLE (P = 0.032). The serum 25(OH)D3 levels, adjusted with BMI, were positively correlated only with hemoglobin (b = 0.256, P = 0.018) and serum complement 3 (b = 0.365, P = 0.002). Serum vitamin D levels were lower, and vitamin D insufficiency was more common in Korean patients with SLE, however, our study demonstrated that vitamin D levels might not be a good marker of disease activity.

ObjectiveTo demonstrate pharmacokinetic equivalence of CT-P10 and innovator rituximab (RTX) in patients with rheumatoid arthritis (RA) with inadequate responses or intolerances to antitumour necrosis factor agents.MethodsIn this randomised phase I trial, patients with active RA were randomly assigned (2:1) to receive 1000 mg CT-P10 or RTX at weeks 0 and 2 (alongside continued methotrexate therapy). Primary endpoints were area under the serum concentration–time curve from time zero to last quantifiable concentration (AUC0–last) and maximum serum concentration after second infusion (Cmax). Additional pharmacokinetic parameters, efficacy, pharmacodynamics, immunogenicity and safety were also assessed. Data are reported up to week 24.Results103 patients were assigned to CT-P10 and 51 to RTX. The 90% CIs for the ratio of geometric means (CT-P10/RTX) for both primary endpoints were within the bioequivalence range of 80%–125% (AUC0–last: 97.7% (90% CI 89.2% to 107.0%); Cmax: 97.6% (90% CI 92.0% to 103.5%)). Pharmacodynamics and efficacy were comparable between groups. Antidrug antibodies were detected in 17.6% of patients in each group at week 24. CT-P10 and RTX displayed similar safety profiles.ConclusionsCT-P10 and RTX demonstrated equivalent pharmacokinetics and comparable efficacy, pharmacodynamics, immunogenicity and safety.Trial registration numberNCT01534884.

To date, the treatment of adult-onset Still's disease (AOSD) has been largely empirical; therefore, this study was conducted to investigate the response to therapy and prognostic factors of AOSD. Fifty-four Korean patients with AOSD were enrolled based on Yamaguchi's criteria. We retrospectively analyzed the treatments and prognosis. Thirty-nine patients (72.2%) were female, and the average age at disease onset was 37.3 years. Twenty-nine patients had a monocyclic disease (53.7%), five had a polycyclic (9.3%) and fifteen had a chronic articular disease (27.7%) and five died (9.3%). The elevated ESR and corticosteroids refractoriness were associated with poor prognosis (P = 0.023 and P = 0.009, respectively). The patients that died were older than those survived (49.2 ± 11.8 vs. 42.2 ± 14 year old, P = 0.024). Forty-two patients were treated with non-steroidal anti-inflammatory drugs; however, they also needed corticosteroids and intravenous immunoglobulin (IVIG). Among 50 patients treated with high-dose corticosteroids, 21 patients (42%) were resistant to corticosteroids and treated with IVIG or anti-tumor necrosis factor (TNF) agents. Of the 23 patients medicated with IVIG, the prognosis was better in IVIG-responsive patients, indicating a therapeutic effect. Methotrexate was the most commonly used disease modifying anti-rheumatic drugs (27 patients, 50%), and the corticosteroid requirements were lower in the methotrexate-responsive patients. Approximately half of AOSD patients had a poor prognosis and were corticosteroids resistance. An elevated ESR and non-response to corticosteroids were associated with poor prognosis. Patients who died were older than those survived.