The etiology of systemic lupus erythematosus (SLE) involves a complex interaction of genetic and environmental factors. Investigations have shown that environmentally driven epigenetic changes contribute to the etiology of SLE. Here, we hypothesize that aberrant DNA methylation may contribute to the activation of the immune machinery and trigger lupus disease activity. A whole genome methylation array was applied to investigate the DNA methylation changes between 12 pairs of active SLE patients and healthy controls. The results were further confirmed in 66 SLE patients, 102 healthy controls. The methylation statuses of the IL10 and IL1R2 genes were significantly reduced in the SLE patient samples relative to the healthy controls (age-adjusted odds ratios, 64.2 and 16.9, respectively, Po0.0001). There was a trend toward SLE patients having hypomethylated IL10 and IL1R2 genes accompanied by greater disease activity. We observed that the methylation degree of IL10 and IL1R2 genes were reduced in the rheumatoid arthritis (RA) patients as well but the hypomethylation change was more significant in IL1R2 genes than in the IL10 genes in RA patients. This study demonstrated that DNA hypomethylation might be associated with SLE. Hypomethylated IL10 and IL1R2 genes may provide potential epigenetic markers as clinical predictors for autoimmune diseases.

We investigated whether premature telomeric loss occurred in peripheral polymorphonuclear neutrophils (PMN) as well as mononuclear cells (MNC) from patients with systemic lupus erythematosus (SLE). We measured the telomere length of MNC and PMN in 60 SLE patients and 26 sex-, race- and age-matched healthy volunteers by Southern blotting with chemiluminescence method. The possible predisposing factors associated with telomere change were also analysed. We found the telomere length of MNC and PMN shortened with age in different degrees in both SLE and control groups. Compared to the control group, the telomere length was shortened in both SLE-MNC (6.08 kb in SLE versus 6.71 kb in control, P = 0.0008) and PMN (6.24 kb in SLE versus 6.75 kb in control, P = 0.0025). The average reduction in telomere length in SLE patients was equivalent to a premature senescence of 16.5 years in MNC and 13.4 years in PMN. In addition, the accelerated telomere shortening was more prominent in SLE patients younger than 45 years old. SLE disease activity (SLEDAI) contributed remarkably to the accelerated telomere erosion, at least in PMN. Moreover, the telomere length of MNC was significantly shorter than PMN in the same SLE patients with leukopenia and lymphopenia. These data suggested that MNC and PMN from patients with SLE displayed premature and accelerated telomere shortening that SLE is an independent factor for it.

Scenarios were identified using the top 13 organ involvement combinations, then patients were grouped into 7 categories based on GC dose and 10 patients per category were selected. Scenario information included: SLEDAI-2K score, organ involvement combination and GC dose.3 rheumatologists ranked disease activity with PGA. An independent cohort was used for the validation in phase 3. We hypothesised that in patients with improvement/worsening by SLEDAI-2K, the change in SLEDAI-2K and SGI will correlate. Results Scenario development is summarised in table 1. 131 scenarios were ranked by 3 rheumatologists leading to 393 records. Perfect LS agreement was achieved; ICC (2, k) of 0.89 (95% CI: 0.83, 0.89). A quadratic linear regression model relating GC and SLEDAI-2K was structured; SGI score=SLEDAI-2K score+[3.65+0.29*GC-0.0027(GC*GC)]. The weight score of GC doses was derived (Table 2). Construct Validity: 109 of the 158 patients improved, 38 remained unchanged, 11 worsened. SLEDAI-2K and SGI correlated highly (r=0.87) and changed in the same direction in patients with improvement/worsening proving the validity of SGI. Conclusions We developed and validated a novel lupus disease activity index, SGI, that describes disease activity while accounting for GC dose. Background and aims While a "Treat-to-target" principle is widely advocated in management of systemic lupus erythematosus (SLE), there is currently no internationally agreed definition of low disease activity in lupus. In 2015, the Asia-Pacific Lupus Collaboration presented a novel consensus definition of a safe state in lupus, the "Lupus Low Disease Activity State" (LLDAS). (http://dx.doi.org/10.1136/annrheumdis-2015-207726) Methods This was a prospective study to determine whether LLDAS predicted lower flare-ups, damage and mortality. 339 SLE patients were recruited and followed for 30 months. Multivariable binomial regression was used to determine factors associated with LLDAS and Cox proportional hazard model to determine whether prior higher% of days in LLDAS would be associated with lower future flare-ups. Results Mean patient age was 48.1 years and mean disease duration 19.6 years. Female to male ratio=16 to 1. 79 flareups were documented. 92.6% of patients had ever achieved LLDAS during the study period and 62.1% of patient-days were in LLDAS. No major demographic or prior disease presentations were found to be associated with the attainment of LLDAS. Patients with prior higher percentage of days in LLDAS had lower hazard of lupus flare-ups (HR=0.420, p=0.015) after adjustment for gender and age. The numbers of patient damage and death were insufficient for analysis. Conclusions LLDAS is an independent construct achievable by most patients of different history or background. Our preliminary study shows LLDAS can predict the risk of future flareups though further studies are needed to determine whether it is associated less lupus-related damage and lower mortality. Neuropsychiatric lupus manifestations, especially the common disorders of mood and cogniti...