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OBJECTIVE Small fiber neuropathy (SFN) is clinically and etiologically heterogeneous. Although autoimmunity has been postulated to be pathophysiologically important in SFN, few autoantibodies have been described. We aimed to identify autoantibodies associated with idiopathic SFN (iSFN) by a novel high-throughput protein microarray platform that captures autoantibodies expressed in the native conformational state. METHODS Sera from 58 SFN patients and 20 age- and gender-matched healthy controls (HCs) were screened against >1,600 immune-related antigens. Fluorescent unit readout and postassay imaging were performed, followed by composite data normalization and protein fold change (pFC) analysis. Analysis of an independent validation cohort of 33 SFN patients against the same 20 HCs was conducted to identify reproducible proteins in both cohorts. RESULTS Nine autoantibodies were screened with statistical significance and pFC criteria in both cohorts, with at least 50% change in serum levels. Three proteins showed consistently high fold changes in main and validation cohorts: MX1 (FC��=���2.99 and 3.07, respectively, p��=���0.003, q��=���0.076), DBNL (FC��=��2.11 and 2.16, respectively, p��=���0.009, q��

Systemic lupus erythematosus (SLE) is an autoimmune disease with protean manifestations that predominantly affects young women. Certain ethnic groups are more vulnerable than others to developing SLE and experience increased morbidity and mortality. Reports of the global incidence and prevalence of SLE vary widely, owing to inherent variation in population demographics, environmental exposures and socioeconomic factors. Differences in study design and case definitions also contribute to inconsistent reporting. Very little is known about the incidence of SLE in Africa and Australasia. Identifying and remediating such gaps in epidemiology is critical to understanding the global burden of SLE and improving patient outcomes. Mortality from SLE is still two to three times higher than that of the general population. Internationally, the frequent causes of death for patients with SLE include infection and cardiovascular disease. Even without new therapies, mortality can potentially be mitigated with enhanced quality of care. This Review focuses primarily on the past 5 years of global epidemiological studies and discusses the regional incidence and prevalence of SLE and top causes of mortality. In this Review, the authors summarize and discuss the existing evidence on the incidence, prevalence and mortality of systemic lupus erythematosus across different world regions, with a focus on studies from the past 5 years.

Objectives Brain white matter (WM) microstructural changes evaluated by diffusion MRI are well documented in patients with SLE. Yet, the conventional diffusion tensor imaging technique fails to differentiate WM changes that originate from tissue alterations from those due to increased extracellular free water (FW) related to neuroinflammation, microvascular disruption, atrophy, or other extracellular processes. Here, we sought to delineate changes in WM tissue microstructure and extracellular FW volume and examine their relationships with neurocognitive function in SLE patients. Methods Twenty SLE patients [16 females, aged 36.0 (10.6)] without clinically overt neuropsychiatric manifestation and 61 healthy controls (HCs) [29 females, aged 29.2 (9.4)] underwent diffusion MRI and computerized neuropsychological assessments cross-sectionally. The FW imaging method was applied to compare microstructural tissue changes and extracellular FW volume of the brain WM between SLE patients and HCs. Association between extracellular FW changes and neurocognitive performance was studied. Results SLE patients had higher WM extracellular FW compared with HCs (family-wise-error-corrected P Conclusion The association between WM extracellular FW increases and reduced neurocognitive performance suggest possible microvascular degradation and/or neuroinflammation in SLE patients with clinically inactive disease. The mechanistic impact of cumulative glucocorticoids on WM FW deserves further evaluation.

Cognitive dysfunction (CD) is a common yet often clinically subtle manifestation that considerably impacts the health-related quality of life in patients with systemic lupus erythaematosus (SLE). Given the inconsistencies in CD assessment and challenges in its attribution to SLE, the reported prevalence of CD differs widely, ranging from 3 to 88%. The clinical presentation of CD in SLE is non-specific and may manifest concurrently with overt neuropsychiatric illness such as psychosis or mood disorders or as isolated impairment of attention, working memory, executive dysfunction or processing speed. Despite the lack of standardized and sensitive neuropsychological tests and validated diagnostic biomarkers of CD in SLE, significant progress has been made in identifying pathogenic neural pathways and neuroimaging. Furthermore, several autoantibodies, cytokines, pro-inflammatory mediators and metabolic factors have been implicated in the pathogenesis of CD in SLE. Abrogation of the integrity of the blood-brain barrier (BBB) and ensuing autoantibody-mediated neurotoxicity, complement and microglial activation remains the widely accepted mechanism of SLE-related CD. Although several functional neuroimaging modalities have consistently demonstrated abnormalities that correlate with CD in SLE patients, a consensus remains to be reached as to their clinical utility in diagnosing CD. Given the multifactorial aetiology of CD, a multi-domain interventional approach that addresses the risk factors and disease mechanisms of CD in a concurrent fashion is the favourable therapeutic direction. While cognitive rehabilitation and exercise training remain important, specific pharmacological agents that target microglial activation and maintain the BBB integrity are potential candidates for the treatment of SLE-related CD.

Objectives The impact of glucocorticoids on neurocognitive performance in patients with SLE is not fully addressed. We aimed to study the effect of daily and cumulative glucocorticoid dose on neurocognitive performance in SLE patients. Methods Consecutive SLE patients and gender- and age-matched healthy controls (HCs) underwent the computer-based Automated Neuropsychological Assessment Matric (ANAM), which evaluates eight neurocognitive domains including learning, recall, visual perception, mental rotation, short-term memory, attention, sustained attention and working memory. The total and individual-domain throughput scores (TPSs) and the presence of cognitive dysfunction (total TPS Results A total of 96 SLE patients and 96 HCs were studied. SLE patients scored significantly worse across all the neurocognitive domains and had a significantly lower mean total TPS (P 9 mg daily remained independently associated with lower mathematical-processing TPSs (P = 0.031). Conclusion Daily prednisolone dose ≥9 mg, but not cumulative glucocorticoid dose, had an independent negative impact on mathematical processing in SLE patients.

Objectives Despite the widespread adoption of teleconsultations amid the COVID-19 pandemic, their safety in SLE patients has not been evaluated. Here, we examined subsequent disease activity and flares among SLE patients who received teleconsultation vs in-person consultation. To discern differences in physicians’ prescription behaviour during both forms of consultations, we compared corticosteroid dose adjustments. Methods We studied adult SLE patients who were seen between 1 February 2020 and 1 February 2021. At each patient-visit, rheumatologists utilized phone/video teleconsultation or physical consultation at their discretion. Disease activity was assessed with SLE Disease Activity Index 2000 (SLEDAI-2K) and flares were defined by the SELENA-SLEDAI Flare Index (SFI). We derived a propensity score for patients who were chosen for physical consultation. Multivariable generalized estimation equations were used to analyse SLEDAI-2k and flare at the next visit, adjusted for the propensity score. Results A total of 435 visits were recorded, of which 343 (78.9%) were physical visits and 92 (21.1%) were teleconsultations. The modality of consultation did not predict flare [OR for physical consultation (95% CI) 0.42 (0.04, 5.04), P =0.49] or SLEDAI-2k at the next visit [estimate of coefficient for physical consultation (95% CI) −0.19 (−0.80, 0.43), P =0.55]. Adjustments of prednisolone dosages were comparable between the two forms of visits [OR for physical consultation (95% CI) 1.34 (0.77, 2.34), P =0.30]. Conclusion SLE disease activity and flares at the subsequent visit were similar between teleconsultations and physical consultations. Medication prescription behaviour, determined using adjustment in corticosteroid dosages, was not different between the two forms of visits.

Objective Conventional immunoassays detect autoantibodies related to systemic lupus erythematosus (SLE) via recognition of epitopes on autoantigens expressed in their denatured rather than native conformational state, casting difficulty in evaluating the genuine pathogenicity of the autoantibodies. We aimed to use a novel high-throughput protein microarray platform to identify autoantibodies against native autoantigens in SLE sera. Methods Sera from SLE patients and those of gender-, age-, and ethnicity-matched healthy controls (HC) were screened against more than 1,600 immune-related antigens of native conformation. The relative fluorescent unit readout from post-assay imaging were subjected to bioinformatics pre-processing and composite normalization. A penetrance fold change (pFC) analysis between SLE and HC samples shortlisted 50 autoantigens that were subjected to an unsupervised cluster analysis. Correlations between the pFC of putative autoantigens and clinical parameters including SLE disease activity index (SLEDAI-2K) and recent SLE flares were explored. Results 381 autoantigens were identified when 15 SLE and 15 HC serum samples were compared. The top 20 autoantigens which elicited autoantibody responses in SLE sera filtered based on the highest pFC were further analyzed. Autoantigens which the putative autoantibodies reacted against are those involved in chromatin organization such as DEK, regulation of transcription activity including REOX4 and ELF4, and negative regulation of NFkB activity such as TRIB3. Additionally, the pFC of these autoantibodies significantly and positively correlated with SLEDAI-2K and recent SLE flares. Conclusion A high-throughput protein microarray platform allows detection and quantification of putative lupus-related autoantibodies which are of potential pathophysiological and prognostic significance in SLE patients.

Objective.To evaluate attitudes and behaviors of patients with rheumatic diseases during the coronavirus disease 2019 (COVID-19) pandemic.Methods.An online survey delivered by text message to 4695 patients on follow-up at a tertiary rheumatology center. Latent class analysis was performed on the survey variables.Results.There were 2239 (47.7%) who responded to the survey and 3 clusters were identified. Cluster 3 (C3) was defined by patients who were most worried about COVID-19, more likely to wear face masks, and more likely to alter or stop their medications. Patients in C3 were more likely to be female, Malay, and unemployed.Conclusion.We identified 3 clusters with different healthcare beliefs and distinct sociodemographics.

Objectives To identify and quantify the level of CD34+CD133+CD309+ circulating angiogenic cells (CAC) and explore factors associated with the level of CAC in patients with SLE. Methods The peripheral blood mononuclear cells of consecutive SLE patients and demographically matched healthy controls (HC) were extracted and identified, enumerated and compared for CAC levels by multi-colour flow cytometry based on the EULAR Scleroderma Trials and Research (EUSTAR) recommendation. Meta-analyses were performed by combining the current and previous case–control studies, aiming to increase the statistical power to discern the difference in CAC level between SLE patients and HC. Mixed-model meta-regression was conducted to explore potential demographic and clinical factors that were associated with CAC level. Results A lower level of CAC was found in 29 SLE patients compared with 24 HC [mean (s.d.) 10.76 (13.9) vs 24.58 (25.4) cells/ml, P = 0.015]. Random-effects meta-analyses of the current and six previously published case–control studies involving 401 SLE patients and 228 HC revealed a lower CAC level compared with HC (standardized mean difference = –2.439, P = 0.001). Meta-regression analysis demonstrated that HCQ use was associated with a more discrepant CAC level between both groups (P = 0.01115). Conclusion SLE patients had a significantly lower CD34+CD133+CD309+ CAC level than HC, and HCQ use was associated with a more discrepant CAC level between SLE patients and HC. This study triggers further observational, interventional and mechanistic studies to address the beneficial impact of HCQ on the functionality of CAC in SLE patients.

Since its description in 1990, Takotsubo syndrome (TTS), an acute cardiac condition triggered by physical or emotional stress, has been believed to be related to catecholamine surge from overwhelming sympathetic activity. While symptomatology, biochemical features, ECG and echocardiogram alterations are largely indistinguishable from acute coronary syndrome, the absence of culprit coronary lesions often necessitates further investigations, uncovering underlying inflammatory processes. Mechanistically, animal models of TTS reveal early neutrophil infiltration followed by staged ingression of two subtypes of macrophages (M1, M2) mediating initial acute inflammatory changes (M1), followed by switching to anti-inflammatory signals (M2) that enhance myocardial tissue recovery. Here, we begin with a description of two TTS patients with primary Sjögren’s syndrome and Takayasu’s arteritis, followed by a systematic literature review that summarizes the demographic and clinical features of TTS patients with rheumatological conditions. Potential impact of disease manifestations and treatment of rheumatological conditions on TTS are critically discussed.

The signalling lymphocyte activation molecule (SLAM) family receptors play important roles in modulating immune responses. Previous studies in murine models and patients have suggested an association of the SLAM family (SLAMF) members with the development of autoimmunity, particularly systemic lupus erythematosus (SLE). Since previous investigations on CD244 expression have focussed on NK and T cells, the aim of this study was to evaluate the surface expression of major SLAMF members across monocytes and polymorphonuclear cells in an Asian SLE cohort and explore their potential associations with SLE-related disease activity and autoantibodies. Thirty-nine SLE patients and twenty-nine healthy controls (HC) were evaluated for the expression of CD150, CD84, CD229, CD48, CD244, CD352 and CD319. We determined a significantly lower expression of CD244 on monocytes in SLE patients compared to HC. Furthermore, monocyte CD244 expression was negatively associated with several serum autoantibody titres. Our findings suggest that this molecule plays an important role in immune tolerance mechanisms and should be investigated further. Electronic supplementary material The online version of this article (doi:10.1007/s10067-017-3698-2) contains supplementary material, which is available to authorized users.

Background/purpose Neuropsychiatric (NP) events are found in patients with rheumatic diseases, commonly in systemic lupus erythematosus (SLE) and Sjogren's syndrome (SS). The standard nomenclature and case definitions for 19 NPSLE syndromes by the American College of Rheumatology (ACR) Committee on Research cover a wide range of NP events seen in both SLE and SS. Despite advances in the understanding of SLE and SS, NP syndromes continue to pose diagnostic challenges. Correct attribution of NP events is critical in determining the correct treatment and prognosis. Anti-N-methyl- d -aspartate receptor subunits NR2A/B (anti-NR2A/B) antibodies have been demonstrated in the sera of SLE and SS patients and have been associated with collective or specific NP syndromes, though not consistently. Interpretation of anti-NR2A/B antibody data in the medical literature is rendered difficult by small sample size of patient groups. By combining different studies to generate a pooled effect size, a meta-analysis can increase the power to detect differences in the presence or absence of NP syndromes. Hence, we set out to perform a meta-analysis to assess the association between anti-NR2A/B antibodies and NP syndromes in SLE and SS. Methods A literature search was conducted using PubMed and other databases from inception to June 2016. We abstracted data relating to anti-NR2A/B antibodies from the identified studies. The random effects model was used to calculate overall combined odds ratio (OD) with its corresponding 95% confidence interval (CI) to evaluate the relationship between anti-NR2A/B antibodies and NP syndromes in SLE and SS patients with and without NP events. We also included our own cohort of 57 SLE patients fulfilling the ACR 1997 revised classification criteria and 58 healthy controls (HCs). Results In total, 17 studies with data on anti-NR2A/B antibodies in 2212 SLE patients, 66 SS patients, 99 disease controls (DCs) (e.g. antiphospholipid syndrome, myasthenia gravis and autoimmune polyendocrine syndrome I) and 538 HCs were used in this analysis. Overall pooled prevalence of serum/plasma anti-NR2A/B antibodies was higher in SLE patients [24.6% (95% CI 18.5–32.0%)] and SS patients [19.7% (95% CI 11.8–31.0%)] compared to DCs [14.8% (95% CI 2.2–56.9)] and HCs [7.6% (95% CI 4.6–12.4%)] (p = 0.001). There was a significantly greater proportion of SLE and SS patients with NP syndromes who demonstrated positivity for serum/plasma anti-NR2A/B antibody [pooled OR = 1.607 (95% CI 1.041–2.479), p = 0.032] as compared to SLE and SS patients without NP syndromes in 13 studies. Usable data for cerebrospinal fluid anti-NR2A/B antibodies were available in only 4 studies [pooled OR = 0.831 (95% CI 0.365–1.888), p = 0.658]. Among the 19 NP syndromes, serum/plasma anti-NR2A/B antibodies were not specifically associated with any NP syndrome, including cognitive dysfunction (p = 0.259) and mood disorder (p = 0.503). Meta-regression identified proportion of anti-double-stranded deoxyribonucleic acid antibody positivity (p = 0.009) and SLE Disease Activity Index (p = 0.028) as moderators for the heterogeneity of serum/plasma anti-NR2A/B antibodies. Conclusion Circulating anti-NR2A/B antibody testing has a diagnostic value for NP syndromes in SLE and SS collectively. However, the evidence to date suggests that anti-NR2A/B antibody positivity cannot distinguish specific NP syndromes.

Background:Anti-carbamylated protein antibody (anti-carp) positivity has been associated with poorer outcomes in Western cohorts of early rheumatoid arthritis; however, it is unknown if this applies to Asians.Objectives:We determined whether anti-carp predicted DAS28-remission, disability and radiographic progression in a multi-ethnic Asian ERA cohort.Methods:Patients with physician diagnosed ERA (symptom duration ≤1 year) were recruited from the Singapore Early Arthritis Cohort (n= 317) by convenience sampling. Serum anti-carp was measured cross-sectionally using a commercial ELISA (SincereBio). The test was repeated in 40 healthy individuals to establish the optimal sensitivity and specificity for the diagnosis of RA via a receiver operating curve. Disease activity (DAS28-ESR or DAS28-CRP) was recorded at baseline, 3, 6 and 12 months. Two independent accessors quantified the radiographic damage at baseline and at follow-up using the modified Sharp van der Heijde score (mSS). We used multivariable logistic regression to determine whether anti-carp predicted the following outcomes; (i) DAS-28 remission at 12 months, (ii) any disability (mHAQ>0) at 12 months and (iii) radiographic progression (any increase in the mSS). In each regression model, we chose covariates known to influence the dependent variable in our cohort or from literature.Results:One hundred patients were recruited, of mean age (SD) 49.8 (12.5) years, median (IQR) disease duration 10.2 (6.9-15.1) weeks at cohort entry and baseline median DAS-28 4.5 (2.9-5.9) (Table 1). The anti-carp assay was performed after a median (IQR) disease duration of 2.24 (1.82-3.14) years. 93 patients had baseline hand radiographs and 66 had follow-up hand radiographs after ≥ 12 months. Receiver operating characteristics curve yielded optimal sensitivity (95%) and specificity (60%) for the diagnosis of RA at 1.60OD. Therefore, 60 patients were anti-carp positive and 35 patients (37.2%) were positive for RF, ACPA and anti-carp (Figure 1). Anti-carp positivity independently predicted DAS28-remission at 12 months (OR 3.41, 95% CI 1.08-10.7,p=0.04) (Table 2). Anti-carp positivity did not predict disability at 12 months (OR 0.61, 95% CI 0.18-2.07,p=0.43) or radiographic progression (OR 0.23, 95% CI 0.03-2.03,p=0.18).Table 1.Predictors of DAS28-remission at 12 monthsVariableN (%)Univariable Logistic RegressionMultivariable Logistic RegressionORpOR (CI)SEpAnti-carp60 (60)3.0 (1.31−6.88)0.013.41 (1.08−10.7)1.990.04SerologyRF and ACPA negative31 (33.0)RefEither RF or ACPA positive11 (11.7)0.99 (0.25−3.93)0.991.10 (0.17−7.04)1.040.92RF and ACPA positive52 (55.3)1.12 (0.45−2.75)0.800.89 (0.28−2.81)0.520.84Baseline DAS28Remission17 (17.4)RefLow DA10 (10.2)0.50 (0.05−4.67)0.540.13 (0.01−1.67)0.170.12Mod DA32 (32.7)0.29 (0.05−1.65)0.160.10 (0.02−0.68)0.100.02High DA39 (39.8)0.18 (0.04−0.90)0.040.06 (0.01−0.41)0.06Combination csDMARDs or biologic DMARD74 (74)1.13 (0.46−2.76)0.801.97 (0.58−6.67)1.230.28Radiographic damage at baseline11 (20)1.79 (0.65−4.95)0.261.27 (0.33-4.95)0.880.73Tertiary education23 (38.3)0.77 (0.34-1.77)0.540.42 (0.12-1.45)0.270.17EthnicityChinese42 (70)RefMalay39 (68.4)0.61 (0.22-1.71)0.350.56 (0.14-2.25)0.400.41Indian8 (13.3)0.60 (0.20-1.77)0.350.79 (0.20-3.13)0.560.74Females46 (76.7)0.43 (0.17-1.11)0.080.48 (0.13-1.85)0.330.29Conclusion:Contrary to previous studies done on Western cohorts where anti-carp predicted worse outcomes, anti-carp positivity predicted DAS28-remission at 12 months in our multi-ethnic Asian cohort. This suggests that different genetic and environmental determinants account for anti-carp expression in patients with RA.Disclosure of Interests:Jiacai Cho: None declared, Anselm Mak Speakers bureau: Professor Anselm Mak has been paid as a speaker for Johnson & Johnson., Sachin Agrawal: None declared, Preeti Dhanasekaran: None declared, Lay Kheng Teoh: None declared, Peter Cheung: None declared, Manjari Lahiri Grant/research support from: Manjari Lahiri is the site principal investigator for the Singapore National Biologics Register, which is a multi-pharmaceutical funded register, in which industry sponsors provide support through the Chapter of Rheumatologists, Singapore. Dr Lahiri does not personally receive any remuneration.

ObjectiveThe association between cigarette smoking and the risk of systemic lupus erythematosus (SLE) remains a matter for debate. Additionally, the effect of the change of smokers’ demographics on the risk of development of SLE over time has not been formally addressed. We aimed to examine the association between cigarette smoking and the risk of SLE by performing an updated metaanalysis.MethodsA literature search using keywords including “lupus,” “smoking,” “cigarette,” “environmental,” “autoimmune,” and “connective tissue disease” was performed in computerized databases to identify studies addressing the relationship between cigarette smoking and SLE occurrence. A Bayesian metaanalysis was conducted by computing the log-OR between current and never smokers, and between former and never smokers. The average log-OR (subsequently converted to OR) and their corresponding 95% credible intervals (CrI) were calculated. The effect of publication time, sex, and age of patients with SLE on the effect sizes was examined by multivariate metaregression.ResultsData aggregation of 12 eligible studies comprising 3234 individuals who developed SLE and 288,336 control subjects revealed a significant association between SLE occurrence and current smoking status (OR 1.54, 95% CrI 1.06–2.25), while only a non-significant trend was demonstrated between SLE occurrence and former smoking status (OR 1.39, 95% CrI 0.95–2.08). Publication time, sex, and the mean age of patients with SLE did not explain the heterogeneity of the effect sizes.ConclusionCurrent smoking status is associated with risk of SLE. Sex and age of patients with SLE had no significant effect on the risk of SLE over time.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of complex etiology that primarily affects women of childbearing age. The development of SLE is attributed to the breach of immunological tolerance and the interaction between SLE-susceptibility genes and various environmental factors, resulting in the production of pathogenic autoantibodies. Working in concert with the innate and adaptive arms of the immune system, lupus-related autoantibodies mediate immune-complex deposition in various tissues and organs, leading to acute and chronic inflammation and consequent end-organ damage. Over the past two decades or so, the impact of genetic susceptibility on the development of SLE has been well demonstrated in a number of large-scale genetic association studies which have uncovered a large fraction of genetic heritability of SLE by recognizing about a hundred SLE-susceptibility loci. Integration of genetic variant data with various omics data such as transcriptomic and epigenomic data potentially provides a unique opportunity to further understand the roles of SLE risk variants in regulating the molecular phenotypes by various disease-relevant cell types and in shaping the immune systems with high inter-individual variances in disease susceptibility. In this review, the catalogue of SLE susceptibility loci will be updated, and biological signatures implicated by the SLE-risk variants will be critically discussed. It is optimistically hoped that identification of SLE risk variants will enable the prognostic and therapeutic biomarker armamentarium of SLE to be strengthened, a major leap towards precision medicine in the management of the condition.

The CD137—CD137 ligand (CD137L) costimulatory system is a critical immune checkpoint with pathophysiological implications in autoimmunity. In this study, we investigated the role of CD137L-mediated costimulation on renal, cutaneous and cerebral manifestations in lupus and the underlying immunological mechanism. Lupus-prone C57BL/6lpr−/− (B6.lpr) mice were crossed to C57BL/6.CD137L−/− mice to obtain CD137L-deficient B6.lpr [double knock out (DKO)] mice. We investigated the extent of survival, glomerulonephritis, skin lesions, cerebral demyelination, immune deviation and long-term synaptic plasticity among the two mouse groups. Cytokine levels, frequency of splenic leukocyte subsets and phenotypes were compared between DKO, B6.lpr and B6.WT mice. A 22 month observation of 226 DKO and 137 B6.lpr mice demonstrated significantly more frequent proliferative glomerulonephritis, larger skin lesions and shorter survival in DKO than in B6.lpr mice. Conversely, microglial activation and cerebral demyelination were less pronounced while long-term synaptic plasticity, was superior in DKO mice. Splenic Th17 cells were significantly higher in DKO than in B6.lpr and B6.WT mice while Th1 and Th2 cell frequencies were comparable between DKO and B6.lpr mice. IL-10 and IL-17 expression by T cells was not affected but there were fewer IL-10-producing myeloid (CD11b+) cells, and also lower serum IL-10 levels in DKO than in B6.lpr mice. The absence of CD137L causes an immune deviation toward Th17, fewer IL-10-producing CD11b+ cells and reduced serum IL-10 levels which potentially explain the more severe lupus in DKO mice while leading to reduced microglia activation, lesser cerebral damage and less severe neurological deficits.

Background: The impact of glucocorticoids on neurocognitive performance in patients with SLE is not fully understood. Objectives: We aimed to study the effect of daily and cumulative doses of glucocorticoids on neurocognitive performance in patients with SLE using the computer-based Automated Neuropsychological Assessment Matric (ANAM). Methods: Consecutive patients with SLE and gender- and age-matched (±5 years) healthy control subject (HC) were studied. In a quiet and comfortable room, each subject underwent the 45-minute ANAM test under supervision which comprises simple reaction time (SRT) that probes neuromuscular efficiency, and 8 domains of neurocognitive assessment including 3 code substitution tests (probing learning and recall), spatial processing (probing visual perception and mental rotation), matching to sample (probing short-term memory and attention), continuous performance test (probing sustained attention), mathematical processing, and memory search (probing working memory). Anxiety and depression were assessed by the Hospital Anxiety and Depression scale (HADS). The total and individual-domain throughput scores (TPS) were compared between both groups using Student’s t test. The presence of cognitive dysfunction, defined as total TPS Results: Ninety-six SLE patients and 96 HC were studied, 16 men (16.7%) were present in each group. The mean age±SD of SLE patients and HC were 36.57±11.4 and 33.61±10.6 years (p=0.073), respectively. The mean±SD duration of SLE, SLEDAI and daily and cumulative prednisolone doses were 98.85±87.4 months, 3.37±3.4, 11.01±13.6mg and 16.92±18.5gm, respectively. SLE patients had a significantly higher mean HADS-anxiety score than HC (6.25±3.3 vs 4.62±3.0, p=0.001) while the mean HADS-depression score was comparable between both groups (p=0.093). SLE patients had significantly shorter duration of education (12.92±3.92 vs 15.86±2.5 years, p Conclusion: Daily, but not cumulative glucocorticoid dose has an independent impact on the working memory of SLE patients. While how daily glucocorticoid dose affects working memory mechanistically requires further investigation, its impact on neurocognitive assessment in SLE patients cannot be underestimated. Disclosure of Interests: None declared

Background: Although remission is the goal of treatment in early rheumatoid arthritis (ERA), there is a lack of a sensitive biomarker for evaluating stringent clinical remission. Calprotectin is a potential biomarker for this purpose as it plays a critical role in synovial inflammation, cartilage destruction and bone resorption and its levels are reflective of local joint inflammation.1,2 Objectives: The study compares calprotectin with acute phase reactants such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in discriminating stringent clinical remission from low disease activity (LDA) to moderate disease activity (MDA) in patients with ERA. Methods: A cross-sectional study was conducted on ERA patients from the Singapore Early Arthritis Cohort study. Serum calprotectin, ESR and CRP levels were measured. Receiver operating characteristics curves were used to compare the biomarkers in determining remission according to the Disease Activity Score in 28 Joints with ESR and CRP (DAS28ESR and DAS28CRP), Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI). Results: Eighty ERA patients were included: 72.5% female, 61.3% Chinese, 66.3% seropositive, mean (S.D.) age 54.1 (12.2) and disease duration 2.3 (0.9) years. Calprotectin was significantly correlated with the DAS28ESR (rs=0.509, P-value Conclusion: Calprotectin is a sensitive biomarker for evaluating stringent clinical remission and can potentially be integrated into treat-to-target algorithms to guide management in ERA patients with apparently quiescent disease activity. References [1] Bae SC, Lee YH. Calprotectin levels in rheumatoid arthritis and their correlation with disease activity: a meta-analysis. Postgrad Med 2017;129(5):531-7. [2] Kopec-Medrek M, Widuchowska M, Kucharz EJ. Calprotectin in rheumatic diseases: a review. Reumatologia 2016;54(6):306-9. Acknowledgement: This work was supported by the National University Hospital University Medicine Cluster Junior Research Award (JRA/Nov17/U002). Disclosure of Interests: Yuhan Zou: None declared, Manjari Lahiri Grant/research support from: Grant support from Pfizer. I am the site PI for the Singapore National Biologics Register which is funded by multiple pharmaceutical companies; however I do not directly receive any funds for this., Consultant for: Advisory board for Elli Lilly, Lay Kheng Teoh: None declared, Bhushan Dharmadhikari: None declared, Nien Yee Kow: None declared, Anselm Mak: None declared, Peter Cheung: None declared

The utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) utility in predicting immune-related adverse events (irAEs) and survival have not been well studied in the context of treatment with immune checkpoint inhibitors (ICIs). We performed a case-control study of cancer patients who received at least one dose of ICI in a tertiary hospital. We examined NLR and PLR in irAE cases and controls. Logistic and Cox regression models were used to identify independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). The study included 91 patients with irAEs and 56 controls. Multiple logistic regression showed that NLR &lt, 3 at baseline was associated with higher occurrence of irAEs. Multivariate Cox regression showed that development of irAEs and reduction in NLR from baseline to week 6 were associated with longer PFS. Higher NLR values at baseline and/or week 6 were independently associated with shorter OS. A reduction in NLR from baseline to week 6 was associated with longer OS. In this study of cancer patients treated with ICIs, NLR has a bidirectional relationship with adverse outcomes. Lower NLR was associated with increased occurrence of irAEs while higher NLR values were associated with worse clinical outcomes.

Background Limited studies have examined the predictors of HRQoL among patients with rheumatoid arthritis. This study helped to ascertain the predictors of HRQoL from the pool of influencing factors identified by previous studies. Aim This study investigated the health-related quality of life (HRQoL) of adult patients with rheumatoid arthritis and its predictors. Methods Using a descriptive correlational design, this study explored the relationship between HRQoL and pain, functional disability, anxiety, depression, medication adherence and social support. Eligible outpatients (n = 108) were recruited via their attending doctors who were co-investigators of this study. Informed consent forms were distributed and questionnaires administered in a teaching hub by the main researcher. Results Significant correlations were found between HRQoL and all of the study variables. Pain, functional disability and depression were main predictors of HRQoL. Conclusions Future evidence-based interventions focusing on pain relief, delaying disability or improving functional ability and reducing depressive symptoms are required to enhance the HRQoL of patients with rheumatoid arthritis.

Early scientific and public enthusiasm for hydroxychloroquine (HCQ) as a potential therapy for COVID-19 has prompted over 100 registered trials to date, although its efficacy remains to be demonstrated.1 Unfortunately, accelerated demand for HCQ has the potential to diminish supplies for patients with systemic lupus erythematosus (SLE), which is worrisome due to the known risks of SLE flare after HCQ withdrawal.2 We previously reported that rheumatologists in most Canadian provinces observed HCQ shortages early in the COVID-19 pandemic.3 However, data are lacking on the global experience with HCQ access during the pandemic, specifically in SLE. On 4 May 2020, we distributed an electronic survey to the 42 Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) members affiliated with SLE referral centres (https://sliccgroup.org), with reminders after 1 and 3 weeks. Physicians were asked about experiences with HCQ shortages during the COVID-19 pandemic, and whether they had been contacted by patients and/or pharmacists regarding difficulties accessing HCQ. Physicians who answered ‘yes’ to the latter question were asked to estimate how many and what proportion …

Objectives To determine the extent of end-of-life suffering and predictors of high symptom prevalence in the last one year of life in patients with systemic rheumatic diseases (SRDs) and the extent of supportive care received. Methods We identified adult patients with SRDs who died between 1 April 2006 and 1 April 2016. We collected data within 1 year before their death, on the following: (i) cumulative symptom prevalence, (ii) rates of Advance Care Planning (ACP), Do-Not-Resuscitate (DNR) orders and referral to a palliative physician. We analyzed the predictors of total symptom prevalence and palliative physician referral. Results Of the 161 patients studied, 34.2% had rheumatoid arthritis and 21.6% had systemic lupus erythematosus. Pain (81.4%), anorexia (80.1%) and dyspnea (77%) afflicted the majority of patients. On multivariate analysis, patients of the following profile had higher total symptom prevalence: (i) older age (β = 0.027, SE = 0.013, p = 0.044); (ii) more comorbidities measured by the Charlson Comorbidity Index (β = 0.192, SE = 0.159, p = 0.044); (iii) more admissions (β = 0.263, SE = 0.090, p = 0.004) and (iv) recurrent infections (β = 0.923, SE = 0.423, p = 0.031). Five patients (3.1%) received ACP and 25 (15.5%) were referred to a palliative physician. The median time between referral to palliative medicine and death was 8 days (IQR0-19). Of the 106 (67.5%) who had DNR orders, the median time between DNR and death was 3 days (IQR 0–10). Conclusions Palliative and supportive care is relevant to patients with SRDs at the end-of-life. These patients experienced high physical suffering, particularly those who were elderly, with more comorbidities, hospital admissions and recurrent infections. Rheumatologists and physicians caring for patients with SRDs must be empowered to provide supportive care to these patients at the last phase of life, particularly by facilitating early ACP.

Over the past two decades it has been increasingly recognized that vitamin D, aside from its crucial involvement in calcium and phosphate homeostasis and the dynamics of the musculoskeletal system, exerts its influential impact on the immune system. The mechanistic roles that vitamin D plays regarding immune activation for combating infection, as well as pathologically and mediating autoimmune conditions, have been progressively unraveled. In vitro and in vivo models have demonstrated that the action of vitamin D on various immunocytes is not unidirectional. Rather, how vitamin D affects immunocyte functions depends on the context of the immune response, in the way that its suppressive or stimulatory action offers physiologically appropriate and immunologically advantageous outcomes. In this review, the relationship between various aspects of vitamin D, starting from its adequacy in circulation to its immunological functions, as well as its autoimmune conditions, in particular systemic lupus erythematosus (SLE), a prototype autoimmune condition characterized by immune-complex mediated inflammation, will be discussed. Concurring with other groups of investigators, our group found that vitamin D deficiency is highly prevalent in patients with SLE. Furthermore, the circulating vitamin D levels appear to be correlated with a higher disease activity of SLE as well as extra-musculoskeletal complications of SLE such as fatigue, cardiovascular risk, and cognitive impairment.

Background While the association between cigarette smoking and the occurrence of SLE has been studied over the past two decades, conflicting results have rendered such association controversial. With the global increase in woman smokers and more prospective data addressing the risk of the development of SLE and cigarette smoking being available, it is timely to provide an update on the evidence of the relationship between cigarette smoking and the occurrence of SLE. Objectives To study the association between cigarette smoking and the odds, as well as the risk of SLE occurrence by meta-analyses of case-control and cohort studies. Methods We performed an extensive literature search using the relevant keywords including “systemic lupus erythematosus”; “lupus’; “smoking”; “cigarette smoking”; “environmental”; “autoimmune disease” and “connective tissue disease” in various combinations to identify case-control and cohort studies addressing the relationship between cigarette smoking and SLE published in English in computerised databases including PubMed (from 1966 to , Jan 2018 Embase (1980 to Jan 2018 and Cochrane Central Register of Control Trials (last quarter of 2017). Effect sizes were pooled as odds ratio (OR) and relative risk (RR) and the corresponding 95% CI for case-control and cohort studies, respectively. Heterogeneity was studied by I2. If the effect sizes were associated with low heterogeneity (I2 Results Thirteen relevant studies (10 retrospective case-control and 3 cohort) were selected for these meta-analyses. Data were aggregated based on smoking statuses comprising current, past, ever and never smoking. Analyses of case-control studies revealed significant relationships between the occurrence of SLE and current smoking (OR 1.639 [1.171–2.295], p=0.004, I2=85.8), and ever smoking (OR 1.438 [1.037–1.995], p=0.029, I2=86.3). However, no significant relationship was found between the occurrence of SLE and past smoking (OR 1.208 [0.853–1.711], p=0.286 I2=74.7). While no relationship was found between the development of SLE and current smoking (RR 1.002 [0.680–1.475], p=0.994, I2=51.6), and ever smoking (RR 1.163 [0.944–1.433], p=0.157, I2=0) when the effect sizes of cohort studies were amalgamated, a significant risk in the development of SLE was found amongst ex-smokers compared with never smokers when the prospective data were combined (RR 1.351 [1.085–1.681], p=0.007, I2=28.0). Conclusions Smoking is associated with the occurrence of SLE based on the aggregation of effect sizes from case-control and cohort studies. The higher risk of development of SLE in ex-smokers but not among current and ever smokers compared to never smokers based on prospective data warrants further mechanistic studies to unravel the actual immunologic impact of cigarette smoke on SLE development in different subsets of SLE patients. Disclosure of Interest None declared

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects approximately 1–45.3 per 100,000 people worldwide. Although deaths as a result of active and renal diseases have been substantially declining amongst SLE patients, disease involving the central nervous system (CNS), collectively termed neuropsychiatric systemic lupus erythematosus (NPSLE), remains one of the important causes of death in these patients. Cognitive dysfunction is one of the most common manifestations of NPSLE, which comprises deficits in information-processing speed, attention and executive function, in conjunction with preservation of speech. Albeit a prevalent manifestation of NPSLE, the pathogenetic mechanisms of cognitive dysfunction remain unclear. Recent advances in genetic studies, molecular techniques, neuropathology, neuroimaging and cognitive science have gleaned valuable insights into the pathophysiology of lupus-related cognitive dysfunction. In recent years, a role for autoantibodies, molecular and cellular mechanisms in cognitive dysfunction, has been emerging, challenging our previous concept of the brain as an immune privileged site. This review will focus on the potential pathogenic factors involved in NPSLE, including anti-N-methyl-d-aspartate receptor subunit NR2A/B (anti-NR2A/B) antibodies, matrix metalloproteinase-9, neutrophil extracellular traps and pro-inflammatory mediators. Better understanding of these mechanistic processes will enhance identification of new therapeutic modalities to halt the progression of cognitive decline in SLE patients.

The presence of the lupus erythematosus (LE) phenomenon has been generally conceptualized as an in vitro occurrence where numerous damaged cells are present and substantial nucleo-phagocytosis has occurred. In systemic lupus erythematosus (SLE), the positive LE cell phenomenon has been shown to indicate active disease with major organ involvement which potentially warrants prompt and heavy immunosuppressive therapy. We report a 36-year-old woman with a known history of SLE who presented with fever, left knee effusion, polyserositis, pancytopenia, low complement and high anti-dsDNA antibody levels whose immunosuppressive treatment was escalated in view of the clinically and serologically active SLE, accompanied by the presence of LE cells in her inflammatory yet sterile left knee synovial fluid. Within 3 days of immunosuppressant escalation, her ascites worsened. While microscopic examination of the ascitic fluid also revealed LE cells, culture of the ascitic fluid later grew Candida parapsilosis. The patient subsequently responded to the addition of anti-fungal therapy into her augmented immunosuppressive regime. Coexistence of the LE cell phenomenon and infection in SLE patients has hitherto not been described. This case illustrates that infection remains to be meticulously excluded despite the presence of the LE phenomenon in the context of clinically and serologically active SLE.

OBJECTIVE Patients can potentially monitor disease activity of RA through self-assessed swollen joints (clinical synovitis), but reliability is poor. The objective is to evaluate the use of education by US feedback on the ability of patients to assess for clinical synovitis in RA. METHODS We performed a 6 month, single-centre, randomized controlled trial on patients with established RA to study the effect of education on self-assessment of joints that included initial brief patient training on tender (TJC) and swollen (SJC) joint counts followed by US feedback every 3 months vs standard care without education. Patient and physician independently performed 28-joint counts at each visit. Outcome variables included the percentage of patients with good agreement with physician-derived swollen joints [prevalence-adjusted bias-adjusted kappa (PABAK) >0.6] as well as agreement in the SJC (Bland and Altman 95% limits of agreement), feasibility/patient satisfaction survey and disease activity at 6 months. RESULTS Of the 101 randomized patients, 95 were included (51 in the education arm and 44 in the standard care arm). At 6 months there was a significant difference in the proportion of patients with swollen joint PABAK >0.6 in the education arm compared with standard care (98 vs 85%, P = 0.02). Limits of agreement for the SJC difference between physician and patients were reduced only in the education arm. The training method is considered feasible, with 94% of patients reporting it as useful. A trend of higher rates of disease remission (28-joint DAS

Endothelium-dependent flow-mediated dilation (ED-FMD), a biophysical marker of endothelial dysfunction, is apparently impaired in patients with systemic lupus erythematosus (SLE) but such observation is inconsistent. Here, we assessed and compared the brachial artery ED-FMD (baED-FMD) using ultrasonography between SLE patients without cardiovascular disease and healthy controls (HC) matched for age, gender and body mass index. We then performed a comprehensive meta-analysis of case-control studies which compared baED-FMD between SLE patients and HC by determining the effect size of baED-FMD as standardized mean difference (SMD). Factors associated with the effect size were explored by mixed-model meta-regression. Seventy one SLE patients and 71 HC were studied. SLE patients had lower baED-FMD than HC (3.72 ± 2.8% vs 4.63 ± 3.1%, p = 0.032). Meta-analysis of 25 case-control studies involving 1,313 SLE patients and 1,012 HC with the random effects model revealed lower baED-FMD in SLE patients compared to HC (SMD −1.077, p

SummaryMetabolic syndrome comprises a number of cardiovascular risk factors that increase morbidity and mortality. The increase in incidence of the syndrome among psychiatric patients has been unanimously demonstrated in recent studies and it has become one of the greatest challenges in psychiatric practice. Besides the use of psychotropic drugs, factors such as genetic polymorphisms, inflammation, endocrinopathies and unhealthy lifestyle contribute to the association between metabolic syndrome and a number of psychiatric disorders. In this article, we review the current diagnostic criteria for metabolic syndrome and propose clinically useful guidelines for psychiatrists to identify and monitor patients who may have the syndrome. We also outline the relationship between metabolic syndrome and individual psychiatric disorders, and discuss advances in pharmacological treatment for the syndrome, such as metformin.LEARNING OBJECTIVES•Be familiar with the definition of metabolic syndrome and its parameters of measurement.•Appreciate how individual psychiatric disorders contribute to metabolic syndrome and vice versa.•Develop a framework for the prevention, screening and management of metabolic syndrome in psychiatric patients.

Costimulatory molecules facilitate cross-talks among leukocytes via mutual stimulatory and inhibitory signalling, contributing to diverse immunological outcomes in normal physiological responses and pathological conditions. Systemic lupus erythematosus (SLE) is a complex multi-systemic autoimmune condition in which cellular communication through the involvement of costimulatory molecules is crucial in driving proinflammatory responses from the stage of autoantigen presentation to the subsequent process of pathogenic autoantibody production. While the physiology of the costimulatory systems including OX40-OX40L, CD28/CTLA-4-CD80/86, ICOS-B7RP1 and CD70-CD27 has been relatively well studied in SLE, recent data on the immunopathology of the CD137-CD137 ligand (CD137L) system in murine lupus models and patients with SLE highlight the critical role of this costimulatory system in initiating and perpetuating the diverse clinical and serological phenotypes of SLE. CD137, a membrane-bound receptor which belongs to the tumour necrosis factor receptor superfamily, is mainly expressed on activated T cells. Activation of the CD137 receptor via its interaction with CD137L which is expressed on antigen present cells (APC) including B cells, triggers bi-directional signalling; that is, signalling through CD137 as well as signalling through CD137L (reverse signalling), which further activates T cells and polarizes them to the Th1/Tc1 pathway. Further, via reverse CD137L signalling it enhances differentiation and maturation of the APC, particularly of dendritic cells, which subsequently drive proinflammatory cytokine production. In this review, recent data including our experience in the manipulation of CD137L signalling pertaining to the pathophysiology of SLE will be critically reviewed. More in-depth understanding of the biology of the CD137-CD137L co-stimulation system opens an opportunity to identify new prognostic biomarkers and the design of novel therapeutic approaches for advancing the management of SLE.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune condition that can potentially affect every single organ during the course of the disease, leading to increased morbidity and mortality, and reduced health-related quality of life. While curative treatment is currently non-existent for SLE, therapeutic agents such as glucocorticoids, mycophenolate, azathioprine, cyclosporine, cyclophosphamide and various biologics are the mainstay of treatment based on their immunomodulatory and immunosuppressive properties. As a result of global immunosuppression, the side-effect profile of the current therapeutic approach is unfavourable, with adverse effects including myelosuppression, infection and malignancies. Hydroxychloroquine, one of the very few Food and Drug Administration (FDA)-approved medications for the treatment of SLE, has been shown to offer a number of therapeutic benefits to SLE patients independent of its immunomodulatory effect. As such, it is worth exploring drugs similar to hydroxychloroquine that confer additional clinical benefits unrelated to immunosuppressive mechanisms. Indeed, apart from hydroxychloroquine, a number of studies have explored the use of a few conventionally non-immunosuppressive drugs that are potentially useful in the management of SLE. In this review, non-immunosuppressive therapeutic agents, namely metformin, dipyridamole, N-acetylcysteine and statins, will be critically discussed with regard to their mechanisms of action and efficacy pertaining to their potential therapeutic role in SLE.

Objective Under physiological stress, the membranes of organelles undergo conformational change to tubulo-reticular structures (TRS) for gaining survival advantage. We aim to explore whether TRS formation in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) correlates with more active disease where physiological stress prevails. Methods To mimic the intracellular impact of interferon-alpha (IFN-α) on lymphocytes, human B-lymphocyte cell line was stimulated by recombinant IFN-α in concentrations of 100, 1000 and 10 000 IU/mL for 72 h. TRS within the lymphocytes was then quantified by transmission electron microscopy (TEM). Upon confirming TRS formation under IFN-α influence, PBMCs of lupus patients were isolated, fixed and quantified for TRS under TEM. The frequency of TRS in lupus PBMCs was compared with that of healthy controls and correlated with the clinical SLE disease activity index (SLEDAI). Results After 72 h, an increase in TRS frequency was observed in a dose-response fashion when the human B-lymphocyte cell line was stimulated by increasing concentrations of IFN-α. In lupus patients, their PBMCs had a significantly higher TRS frequency than healthy controls (P = 0.037). The frequency of TRS was positively associated with the SLEDAI (Spearman ρ = 0.632, P = 0.012), which remained statistically significant after adjustment for daily prednisolone dose (Pearson r = 0.747, P = 0.002). Conclusions While the clinical significance of TRS formation in lupus PBMCs deserves further investigation, these preliminary findings suggest a significant relationship between the disease severity of SLE and intracellular physiological stress. These results underscore the potential of TRS in PBMCs as an ultra-structural disease activity biomarker of SLE.

Depressive disorder is treatable but costly, thus influencing quality of life of people.Determine direct and indirect costs incurred by depressive disorder in Singapore.A 1-year prospective naturalistic study was conducted in a university mood disorder center between 2007 and 2008. Patients with primary International Classification of Disease-10 diagnosis of depressive disorder were recruited. Disease costs between mild, moderate and severe depression, and cost predictors were analyzed and determined.Forty nine patients completed the study. Mean annual total costs per patient were US$7638. Indirect costs (81%) dominated the total costs. Approximately 50% of indirect costs were associated with loss of productivity and unemployment. Higher education level, higher mean Hamilton Rating Scale for Depression score and number of suicide attempts were independent variables associated with increased direct costs while mean Hamilton Rating Scale for Depression scale score was an independent variable for indirect costs.Medical cost saving strategies should focus on indirect costs.

Objectives While patients with systemic lupus erythematosus (SLE) have poorer health-related quality of life (HRQoL) and are more depressed than healthy people, the impact of proinflammatory cytokines, particularly tumour necrosis factor-alpha (TNFα), on these unfavourable psychosocial parameters is unclear. We aim to explore potential relationships between lupus-related proinflammatory cytokines, HRQoL and depressive symptoms in patients with SLE. Methods Patients with SLE and age-matched healthy subjects were assessed for HRQoL and depressive and anxiety symptoms by the Short Form Health Survey-36 (SF-36) and Hospital Anxiety and Depression Scale (HADS) respectively. Using multiplex immunoassay, a panel of serum proinflammatory cytokines including TNFα, interleukin (IL)-1β, IL-6, IL-17, IL-23 and IL-33 were determined and compared between both groups. Independent associations between SF-36, serum proinflammatory cytokine levels and HADS scores were studied by regression models. Results In total, 54 patients and 54 healthy controls were studied. Lupus patients had significantly poorer HRQoL ( p Conclusions Higher serum TNFα level is independently associated with poorer HRQoL and more severe depressive symptoms in SLE patients. These associations suggest a potential impact of inflammatory response on depressive symptoms and the quality of life in patients with SLE.

Objective. Siglecs are sialic acid-binding immunoglobulin-like lectins expressed on the surface of immune cells, which participate in the discrimination of self and non-self. We investigated myeloid CD33-related Siglec expression in a cohort of patients with SLE. Methods. Cell surface expression of Siglec-5/14, Siglec-9 and Siglec-10 on peripheral myeloid subsets were analysed from 39 SLE patients using flow cytometry. Genotyping of the Siglec-5/14 locus was also performed. Clinical markers of SLE disease activity, including SLEDAI, serum complement concentrations and serum autoantibodies, were assessed and correlated with Siglec levels. Results. Siglec-14 expression on SLE monocytes (median = 518, interquartile range: 411) was significantly higher when compared with healthy controls (median = 427, interquartile range: 289.3; P < 0.05) and correlated positively with SLEDAI scoring and anti-Sm and anti-SSB autoantibodies (P < 0.05). A negative correlation was determined with patient serum C3 concentrations (P < 0.005). Genotyping of the Siglec-5/14 locus revealed a high frequency of the Siglec-14 null allele across both groups, reflecting the incidence in Asian populations. Conclusion. Our data suggest that the Siglec immunomodulatory molecules, in particular Siglec-14 expression on monocytes, may play an important role in the inflammatory events of SLE. No bias was found with regard to SIGLEC14 genotype in our patient group compared with healthy controls. Larger comparisons of mixed ethnicity might, however, reveal an important role for Siglecs in the pathogenesis of autoimmune disease.

We examined if cerebral volume reduction occurs very early during the course of systemic lupus erythematosus (SLE), and observed prospectively whether gray (GMV) and white matter volumes (WMV) of the brain would improve with lowered SLE disease activity. T1-weighted MRI brain images were obtained from 14 healthy controls (HC) and 14 newly-diagnosed SLE patients within 5 months of diagnosis (S1) and after achieving low disease activity (S2). Whole brain voxel-based morphometry was used to detect differences in the GMV and WMV between SLE patients and HC and those between SLE patients at S1 and S2. SLE patients were found to have lower GMV than HC in the middle cingulate cortex, middle frontal gyrus and right supplementary motor area, and lower WMV in the superior longitudinal fasciculus, cingulum cingulate gyrus and inferior fronto-occipital fasciculus at both S1 and S2. Whole-brain voxel-wise analysis revealed increased GMV chiefly in the prefrontal regions at S2 compared to S1 in SLE patients. The GMV increase in the left superior frontal gyrus was significantly associated with lowered SLE disease activity. In conclusion, GMV and WMV reduced very early in SLE patients. Reduction of SLE disease activity was accompanied by region-specific GMV improvement in the prefrontal regions.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that greatly impacts one’s physical and psychosocial well-being. The purpose of this study was to explore the experiences and support needs of adult patients living with RA. A descriptive qualitative study was conducted, and 16 adults with RA were interviewed from October 2013 to January 2014. The transcribed data were analyzed using thematic analysis. Five themes were identified: altered physical capacity and well-being, psychological and emotional challenges, changes in social life, coping strategies, and support received and further support needs. This study provided insights into the experiences and support needs of patients with RA in Singapore. Physical and psychosocial challenges experienced by patients affected their daily and social activities. Patients’ needs for variety of support should be addressed.

It remains unclear whether anxiety and depressive symptoms are more prevalent in adolescents with asthma when compared with healthy individuals. This meta-analysis aimed to evaluate the difference in the aggregate prevalence of depressive and anxiety symptoms between adolescents with asthma and healthy controls and to explore the underlying moderators that potentially explain the heterogeneity of the effect size. A meta-analysis of published work was performed using the random effects model. The differences in aggregate prevalence of depressive and anxiety symptoms between adolescents with asthma and healthy controls were determined. Meta-regression and subgroup analysis were performed to identify factors that may contribute to heterogeneity. A total of eight studies were eligible for analysis. The aggregate prevalence of depressive and anxiety symptoms was significantly higher among 3546 adolescents with asthma than that of 24,884 controls (depression, 0.27; 95% CI, 0.18.6-0.39 vs. 0.13; 95% CI, 0.09-0.19; anxiety, 0.33; 95% CI, 0.19-0.52 vs. 0.21; 95% CI, 0.12-0.33). The risk of developing depression and anxiety is significantly higher among adolescents with asthma when compared with controls (depression: pooled odds ratio, 2.09; 95% CI, 1.65-2.64; p < 0.001; anxiety: pooled odds ratio, 1.83; 95% CI, 1.63-2.07; p < 0.001). Meta-regression revealed that the proportions of Caucasian (p = 0.008) and smokers (p < 0.001) were significant moderators which explained the significant heterogeneity when comparing the risk of developing depressive symptoms among adolescent asthma patients vs. controls while age, gender, and severity of asthma were not significant. Family doctors, pediatricians, and healthcare providers should formulate strategies to detect depressive and anxiety symptoms in adolescents with asthma and offer psychological interventions to reduce the burden of psychiatric comorbidity.

SummaryCharcoal-burning has become a common method of attempted suicide in Asia and survivors are often intoxicated with carbon monoxide (CO). Reports of the neuropsychiatric aspects of CO poisoning date back to 1914. This article outlines the neuropsychiatric sequelae that have been described secondary to CO poisoning. The underlying pathophysiology and management strategies, including acute management and cognitive rehabilitation, are discussed as these topics are of relevance to psychiatrists.

Background: Pro-inflammatory cytokines are found to be elevated in patients with anxiety and depression but whether their serum levels are related to anxiety and depression is unknown. We used rheumatoid arthritis (RA) as an inflammatory disease model to explore such relationships. Methods: Eighteen RA patients and 18 healthy controls matched for age and gender were assessed for the severity of anxiety and depression with the hospital anxiety and depression scale (HADS). Disease activity of RA and pain were assessed by the Disease Activity Scale (DAS-2)8 and visual analogue scale of pain, respectively. Serum pro-inflammatory cytokine levels, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-17 were determined by enzyme-linked immunosorbant assay. The differences in cytokine levels between RA patients and healthy controls, as well as within the RA group with and without anxiety and depression, were compared by using the Mann–Whitney U-test. The correlations between anxiety, depression and pro-inflammatory cytokines were explored by Spearman’s rank correlation. Multiple linear regression was used to adjust for DAS-28 and pain. Results: Serum TNF-α, IL-6 and IL-17 levels were significantly higher in RA patients than those of healthy subjects (P

Objective This meta-analysis was aimed to evaluate the differences in aggregated prevalence of depressive symptoms among people with chronic obstructive pulmonary disease (COPD) as compared to controls without COPD and to determine underlying moderators to explain potential heterogeneity of prevalence. Methods A meta-analysis of published work was performed using the random effect model. A total of eight studies were identified. We calculated the differences in prevalence proportion of depressive symptoms in patients with COPD versus controls. Meta-regression and subgroup analysis were performed to identify factors that may contribute to heterogeneity. Results The prevalence proportion of depressive symptoms was found to be significantly higher (pooled odds ratio: 2.81; 95% CI: 1.69–4.66) among 39587 individuals with COPD as compared to 39,431 controls (24.6%, 95% CI: 20.0–28.6% vs. 11.7%, 95% CI: 9–15.1%). Meta-regression was conducted to account for the heterogeneity of the prevalence proportion, but moderators like mean age, gender, mean FEV 1 and proportion of current smokers among COPD patients were nonsignificant and could not explain heterogeneity in prevalence of depressive symptoms. Subgroup analyses showed no significant differences based on different methods of assessment of depressive symptoms and countries sampled. Conclusion This meta-analytical review identified higher prevalence of depressive symptoms among COPD patients, and meta-regression showed that demographic and clinical factors were not the determinants of heterogeneity in prevalence of depressive symptoms.

Objective.To assess whether endothelium-dependent and endothelium-independent flow-mediated dilation (FMD) are impaired in patients with systemic lupus erythematosus (SLE) with no history of vascular event; and to determine factors moderating impaired FMD in SLE.Methods.Electronic databases were searched for case-control studies that compared endothelium-dependent and/or endothelium-independent FMD at the brachial artery between SLE patients who were naive for vascular events and matched healthy controls. Effect size as standardized mean difference (SMD) and 95% confidence intervals of FMD between SLE patients and controls was pooled using the inverse variance method. Mixed-model metaregression was performed to identify potential demographic and clinical factors associated with the effect size.Results.Thirteen relevant studies involving 580 patients and 381 matched healthy controls were included. Endothelium-dependent FMD was significantly lower in SLE patients than in controls (SMD −0.832, 95% CI −1.172 to −0.492, p < 0.001). Endothelium-independent FMD, however, did not differ between the 2 groups (SMD −0.179, 95% CI −0.433 to 0.075, p = 0.167). Metaregression revealed that increasing age (r = 0.047, p = 0.037) and duration of SLE (r = 0.008, p = 0.024) at the time of FMD measurement significantly narrowed the difference of endothelium-dependent FMD between patients and controls; whereas sex, smoking, menopause, diabetes mellitus, body mass index, blood pressure, fasting lipid profile, C-reactive protein, and prednisolone use did not.Conclusion.Endothelium-dependent, but not endothelium-independent FMD is significantly impaired in lupus patients who are naive for vascular events. Increasing age and longer disease duration may limit the potential of endothelial reactivity as an indicator of early atherosclerosis in SLE.