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Singapore managed the COVID-19 pandemic in the past three years and gleaned valuable lessons on patient management when the public healthcare system was inundated with COVID-19 patients. There were several initiatives, which included setting up of community treatment facilities to help hospitals manage in-patient loads that did not require acute monitoring, leveraging telemedicine, and developing heuristics to sort patients based on their clinical disposition to various care pathways and to effectively manage patients of different medical needs. These initiatives were implemented in the second year of the epidemic in 2021 and did not include the dormitory-based migrant workers and migrant workers in the construction, maritime and production sectors who were under the care of the Assurance, Care and Engagement Group (ACE) in the Ministry of Manpower that had its own set of treatment management measures. The different care pathways ensured that patients received appropriate levels of care and allowed healthcare facilities to focus on more acute cases. In 2022 alone, 23,159 patients were discharged from community treatment facilities against the background of 1.9 million COVID-19 patients. These initiatives would not be possible without the oversight of an advisory board comprising senior leadership from the healthcare clusters and the Ministry of Health to align clinical governance with medical policies, and prompt and immense support from medical specialist panels. The strong public-private partnership forged in the process was instrumental in the successful operation of community facilities and implementation of patient care protocols, coupled with harnessing information technology and leveraging on emerging data to refine care protocols.

Introduction: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) are used in the diagnosis and prognostication of rheumatoid arthritis (RA). We wanted to determine the specific contributions of RF and ACPA to the biological nature of RA and whether they act synergistically., Methods: We identified 731 patients from our prospective multi-ethnic RA cohort and categorised them into four groups: ACPA-positive, RF-positive, doubly positive and doubly negative. We compared the demographics, Disease Activity Score-28, Health Assessment Questionnaire score, quality of life using Short Form 36 and the use of prednisolone and disease-modifying antirheumatic drugs (DMARDs) of these patient groups., Results: Four hundred and ninety-one patients (67.2%) were ACPA+RF+, 54 (7.4%) were ACPA+RF-, 82 (11.2%) were ACPA-RF+ and 104 (14.2%) were ACPA-RF-. Mean disease duration before the study entry was not different in the four groups. Patients with older age of onset were less likely to be positive for RF and ACPA. Fewer ACPA+RF+ patients were in remission compared to those in the other groups (P < 0.05). Erythrocyte sedimentation rate (ESR) was higher at study entry in the ACPA+RF+ group (40.4 mm/h vs. 30.6-30.9 mm/h, P < 0.05). Prednisolone and number of DMARDs used were higher in the ACPA+RF+ group compared to the doubly negative group. There were no differences in the functional status and quality of life., Conclusions: RA patients who were positive for both ACPA and RF had lower remission rate, higher baseline ESR and required more corticosteroid and DMARD treatment compared to those who were singly positive or doubly negative. Being doubly positive confers a worse outcome to RA patients., Competing Interests: None

Background: The popular statistics-based Genome-wide association studies (GWAS) have provided deep insights into the field of complex disorder genetics. However, its clinical applicability to predict disease/trait outcomes remains unclear as statistical models are not designed to make predictions. This study employs statistics-free machine-learning (ML)-optimized polygenic risk score (PRS) to complement existing GWAS and bring the prediction of disease/trait outcomes closer to clinical application. Rheumatoid Arthritis (RA) was selected as a model disease to demonstrate the robustness of ML in disease prediction as RA is a prevalent chronic inflammatory joint disease with high mortality rates, affecting adults at the economic prime. Early identification of at-risk individuals may facilitate measures to mitigate the effects of the disease., Methods: This study employs a robust ML feature selection algorithm to identify single nucleotide polymorphisms (SNPs) that can predict RA from a set of training data comprising RA patients and population control samples. Thereafter, selected SNPs were evaluated for their predictive performances across 3 independent, unseen test datasets. The selected SNPs were subsequently used to generate PRS which was also evaluated for its predictive capacity as a sole feature., Results: Through robust ML feature selection, 9 SNPs were found to be the minimum number of features for excellent predictive performance (AUC > 0.9) in 3 independent, unseen test datasets. PRS based on these 9 SNPs was significantly associated with (P < 1 × 10 -16 ) and predictive (AUC > 0.9) of RA in the 3 unseen datasets. A RA ML-PRS calculator of these 9 SNPs was developed ( https://xistance.shinyapps.io/prs-ra/ ) to facilitate individualized clinical applicability. The majority of the predictive SNPs are protective, reside in non-coding regions, and are either predicted to be potentially functional SNPs (pfSNPs) or in high linkage disequilibrium (r2 > 0.8) with un-interrogated pfSNPs., Conclusions: These findings highlight the promise of this ML strategy to identify useful genetic features that can robustly predict disease and amenable to translation for clinical application., (© 2023. The Author(s).)

Objectives: The Montreal Cognitive Assessment (MoCA) is an increasingly used screening tool for cognitive impairment. The aim of this study was to examine how MoCA performed in identifying cognitive impairment (CI) domains in SLE patients compared with formal standardized neuropsychological testing (NPT). Factors related to SLE disease, immunologic and psychological state associated with CI were also explored., Methods: This cross-sectional study recruited 50 SLE patients without overt neuropsychiatric manifestations from April 2017 to May 2018. The patients were evaluated with MoCA, formal NPT and the Depression, Anxiety, and Stress Scales (DASS) 42-item self-report questionnaire. Values of sensitivity and specificity were computed for different cut-offs of MoCA within each cognitive domain of NPT and descriptive analysis was used to identify the factors affecting cognitive function., Results: The median score for MoCA was 27.5 (range 22-30). Using a MoCA cutoff of <26, 18 (36%) were identified to have CI using NPT compared to 8 (16%) using MoCA. The most frequently affected cognitive domain was executive functioning with 15 affected patients. Sensitivities and specificities of the MoCA range from 50% to 100% and 5.7% to 16.7%, respectively, across cognitive domains. A lower MoCA cutoff of <25 improve sensitivity of identifying impairment in executive functioning from 60% to 80%. In univariate analysis, DASS scores, disease activity, presence of antiphospholipid antibodies, presence of concurrent autoimmune disease, current, and cumulative corticosteroid therapy did not predict cognitive performance., Conclusion: MoCA may be a useful screening tool to identify the most frequently affected cognitive domain which is executive functioning using a lower cutoff of <25 in SLE patients without overt neuropsychiatric manifestations.

Objective: To develop a hypothesis-free model that best predicts response to MTX drug in RA patients utilizing biologically meaningful genetic feature selection of potentially functional single nucleotide polymorphisms (pfSNPs) through robust machine learning (ML) feature selection methods., Methods: MTX-treated RA patients with known response were divided in a 4:1 ratio into training and test sets. From the patients' exomes, potential features for classifier prediction were identified from pfSNPs and non-genetic factors through ML using recursive feature elimination with cross-validation incorporating the random forest classifier. Feature selection was repeated on random subsets of the training cohort, and consensus features were assembled into the final feature set. This feature set was evaluated for predictive potential using six ML classifiers, first by cross-validation within the training set, and finally by analysing its performance with the unseen test set., Results: The final feature set contains 56 pfSNPs and five non-genetic factors. The majority of these pfSNPs are located in pathways related to RA pathogenesis or MTX action and are predicted to modulate gene expression. When used for training in six ML classifiers, performance was good in both the training set (area under the curve: 0.855-0.916; sensitivity: 0.715-0.892; and specificity: 0.733-0.862) and the unseen test set (area under the curve: 0.751-0.826; sensitivity: 0.581-0.839; and specificity: 0.641-0.923)., Conclusion: Sensitive and specific predictors of MTX response in RA patients were identified in this study through a novel strategy combining biologically meaningful and machine learning feature selection and training. These predictors may facilitate better treatment decision-making in RA management., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Over-expression of common inflammatory mediators in the metabolic syndrome (MetS) and in rheumatoid arthritis (RA) may lead to mutually adverse outcomes., Aim: We investigate the prevalence of MetS in a multi-ethnic population of RA patients and its effect on clinical and patient-reported outcomes., Method: Six hundred sixty RA (561 women) patients from a public-sector specialist clinic in a hospital in Singapore were assessed for MetS according to the 2009 Joint Consensus (JC) and the 2004 National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definitions. Univariable and multivariable regression modelling were used to investigate the associations between patients' demographics with MetS and MetS with RA outcomes., Results: The prevalence of MetS in our RA cohort was 49.4% and 44.9% according to the JC and NCEP ATP III definitions, respectively. The diagnosis of MetS was largely due to hypertriglyceridemia, hypertension, and obesity. MetS was associated with older age (OR 1.06 [95% CI 1.04-1.08]), Malay ethnicity (OR 1.78 [95% CI 1.02-3.09]), or Indian ethnicity (OR 3.07 [95% CI 1.68-5.59]). No significant associations between MetS and RA outcomes were observed. RA patients with MetS are more likely to suffer from stroke and ischemic heart disease., Conclusion: The prevalence of MetS in RA patients in Singapore was almost double that in the general population. MetS does not adversely affect RA outcomes but raises the risks of stroke and heart disease. RA patients, especially those older and of Indian and Malay ethnicities, should be routinely screened for MetS. Any MetS-defining condition should be actively controlled. Key Points • Approximately half of the RA sample from the Singapore RA population can be diagnosed with MetS. • Older patients, and patients of Malay and Indian ethnicities have higher odds of MetS. • MetS does not adversely affect RA outcomes but raises the risks of stroke and heart disease., (© 2021. International League of Associations for Rheumatology (ILAR).)

Background: Major challenges in large scale genetic association studies include not only the identification of causative single nucleotide polymorphisms (SNPs), but also accounting for SNP-SNP interactions. This study thus proposes a novel feature engineering approach integrating potentially functional coding haplotypes (pfcHap) with machine-learning (ML) feature selection to identify biologically meaningful, possibly causative genetic factors, that take into consideration potential SNP-SNP interactions within the pfcHap, to best predict for methotrexate (MTX) response in rheumatoid arthritis (RA) patients., Methods: Exome sequencing from 349 RA patients were analysed, of which they were split into training and unseen test set. Inferred pfcHaps were combined with 30 non-genetic features to undergo ML recursive feature elimination with cross-validation using the training set. Predictive capacity and robustness of the selected features were assessed using six popular machine learning models through a train set cross-validation and evaluated in an unseen test set., Findings: Significantly, 100 features (95 pfcHaps, 5 non-genetic factors) were identified to have good predictive performance (AUC: 0.776-0.828; Sensitivity: 0.656-0.813; Specificity: 0.684-0.868) across all six ML models in an unseen test dataset for the prediction of MTX response in RA patients., Interpretation: Majority of the predictive pfcHap SNPs were predicted to be potentially functional and some of the genes in which the pfcHap resides in were identified to be associated with previously reported MTX/RA pathways., Funding: Singapore Ministry of Health's National Medical Research Council (NMRC) [NMRC/CBRG/0095/2015; CG12Aug17; CGAug16M012; NMRC/CG/017/2013]; National Cancer Center Research Fund and block funding Duke-NUS Medical School.; Singapore Ministry of Education Academic Research Fund Tier 2 grant MOE2019-T2-1-138., Competing Interests: Declaration of Competing Interest CGL, KPL, CCK, SSC, AJWL, and LJL declare that they have a pending Coversheet IP application., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: We evaluated the impact of type 2 diabetes mellitus (T2DM) on RA treatment and outcomes in a longitudinal RA cohort., Methods: We analysed data collected in the period 2001-2013 involving 583 RA patients, including demographics, diabetes diagnosis, clinical features, treatment, ACR functional class, HAQ, and quality-of-life measurement using the Short-Form 36., Results: Seventy-seven (13.2%) of the RA patients had T2DM. DAS28 was not different in patients with T2DM at 5 years post-RA diagnosis. Fewer T2DM patients received MTX than those without T2DM (51% vs 80%, P < 0.001). Using univariate analysis, T2DM patients were more likely to experience poorer outcomes in terms of ACR functional status ( P = 0.009), joint surgery ( P = 0.007), knee arthroplasty ( P < 0.001) and hospital admissions ( P = 0.006). Multivariate regression analyses showed more knee arthroplasty ( P = 0.047) in patients with T2DM., Conclusion: Fewer patients with T2DM received MTX compared with those without T2DM. Patients with RA and T2DM were at higher risk of knee arthroplasty than RA patients without T2DM., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: This study aims to uncover variants of large effect size and allele frequency below 5% by sequencing all extant genes associated with rheumatoid arthritis (RA) in a homogeneous patient cohort., Patients and Methods: This retrospective study was conducted between January 2001 and December 2017. We selected Chinese RA patients positive for anti-citrullinated peptide antibody (ACPA). All the 128 known candidate genes identified through genome-wide association studies were sequenced in 48 RA patients (15 males, 33 females; mean age 53.32±8.98 years; range, 32 to 75 years) and 45 controls (11 males, 34 females; mean age 32.18±9.54; range, 21 to 57 years). The exonic regions of these genes were sequenced. The resultant data were analyzed for association using single variant association and pathway-based association enrichment tests. The genetic burden due to low-frequency variants was assessed with the C-alpha test. The candidate variants that showed significant association were validated in a larger cohort of 500 RA cases (71 males, 429 females; mean age 48.6±12.2 years; range, 24 to 92 years) and 500 controls (66 males, 434 females; mean age 32.3±10.1 years; range, 21 to 73 years)., Results: Thirty-nine variants in 21 genes were identified using single variant association analysis and C-alpha test, with stepwise filtering. Among these, the missense variant in interleukin-6 signal transducer (IL-6ST) 5:55260065 (p.Cys47Phe) was significantly associated with RA in Chinese patients in Singapore., Conclusion: Our results suggest that a mutation in IL-6ST (5:55260065) confers risk of RA in Chinese patients in Singapore., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2021, Turkish League Against Rheumatism.)

Feature selection (marker gene selection) is widely believed to improve clustering accuracy, and is thus a key component of single cell clustering pipelines. Existing feature selection methods perform inconsistently across datasets, occasionally even resulting in poorer clustering accuracy than without feature selection. Moreover, existing methods ignore information contained in gene-gene correlations. Here, we introduce DUBStepR (Determining the Underlying Basis using Stepwise Regression), a feature selection algorithm that leverages gene-gene correlations with a novel measure of inhomogeneity in feature space, termed the Density Index (DI). Despite selecting a relatively small number of genes, DUBStepR substantially outperformed existing single-cell feature selection methods across diverse clustering benchmarks. Additionally, DUBStepR was the only method to robustly deconvolve T and NK heterogeneity by identifying disease-associated common and rare cell types and subtypes in PBMCs from rheumatoid arthritis patients. DUBStepR is scalable to over a million cells, and can be straightforwardly applied to other data types such as single-cell ATAC-seq. We propose DUBStepR as a general-purpose feature selection solution for accurately clustering single-cell data., (© 2021. The Author(s).)

Objective: Disease activity indices for rheumatoid arthritis (RA) are important in clinical practice and research. Although they are closely correlated, they are not in good agreement. We derived formulae to convert values from one of the four 28-joint count indices (disease activity score using erythrocyte sedimentation rate [DAS28-ESR], disease activity score using C-reactive protein [DAS28-CRP], clinical disease activity index [CDAI], and simple disease activity index [SDAI]) to any of the others., Methods: We obtained data from 175 patients from our RA registry with concurrent CRP and ESR and established the nature of relationships between the indices using these data. Subsequently, we developed empiric conversion formulae. Furthermore, we developed new cutoff values for classifying disease activity to minimize the disparity among indices, using an iterative method., Results: The relationships between DAS28-ESR and DAS28-CRP and between SDAI and CDAI were approximately linear; the others were quadratic. Quadratic equations approximated the relationship between DAS, SDAI, and CDAI, whereas natural logarithms function approximated the relationship between DAS28-ESR and DAS28-CRP. Patients are frequently categorized into inconsistent disease activity states with any two indices, with the disparity ranging from 9.7% to 40.6%. The new cutoff values were developed to minimize the discrepant activity state categorization, reducing the disparity range to 6.3%-32.6%., Conclusion: We derived empiric formulae that connect DAS28-ESR, DAS28-CRP, SDAI, and CDAI. Moreover, we developed new cutoff values to minimize the discrepant activity state categorization with different indices.

Objective: Urinary tract endometriosis involves the bladder and/or the ureters and is present in approximately 1% of women with endometriosis [1]. Bladder endometriosis is the most frequent type of urinary tract endometriosis, occurring in about 70% to 85% of cases [2,3]. Bladder endometriosis is defined as the presence of endometrial glands and stroma in the detrusor muscle. Surgically, there are 2 ways of excising this disease. The first is by transurethral bladder resection of the tumor, and the second is laparoscopic/robotic/open partial cystectomy of the bladder endometriosis. Because the nodule develops from the outer layer of the bladder wall toward the inner layer, complete excision of the endometriotic lesion is virtually unachievable with transurethral resection surgery. There is also a high risk of bladder perforation [4-8]. Partial cystectomy of the bladder runs a risk of excising normal bladder tissues because it is difficult to ascertain the margins of the bladder nodule. However, we found the best method to deal with bladder endometriosis is a combined approach whereby the margins of the bladder nodule are cut via a cystoscopy and then excision of the bladder nodule is done laparoscopically. This particular technique is presented here with an accompanying video., Design: Excision of bladder endometriosis by first delineating the tumor via cystoscopy and simultaneously excising the nodule laparoscopically SETTING: Mahkota Medical Centre, Melaka, Malaysia., Intervention: Here we describe a simultaneous cystoscopic and laparoscopic excision of bladder endometriosis. The patient was first seen in 2005 at age 19 years with an endometrioma. She was single (virgo intacta) at that time. She underwent a laparoscopic cystectomy. Postoperatively, she received 3 doses of monthly gonadotropin-releasing hormone (GnRH) analogue injection. She was last seen in 2006 and was well. She conceived spontaneously after that and delivered 2 babies spontaneously in 2007 and 2010 in another city. She consulted me again in April 2016 complaining of dysuria, dysmenorrhea, and inability to hold her urine. She had consulted a urologist 6 months earlier. Cystoscopy performed by the urologist showed bladder endometriosis. No further surgery was performed, and she was given GnRH analogues for 6 months. However, her symptoms persisted after completion of the GnRH analogue. Examination and ultrasound showed a large bladder nodule measuring 4.17 × 2.80 cm. Intravenous urogram showed stricture in the upper right ureter. She underwent a combined urology and gynecology surgery to excise the bladder nodule. Informed consent was obtained from the patient, and the local institutional board provided the approval. The surgery was performed with the patient in the dorsosacral position. A Verres needle was inserted into the abdomen at the umbilicus, and carbon dioxide insufflation was performed. A 10-mm trocar was inserted in the umbilicus, and a 3-dimensional laparoscope (Aesculup-BBraun Einstein Vision; BBraun, Melsungen AG, Germany) was inserted to view the pelvis. Three 5-mm trocars were inserted, 1 on the right side and 2 on the left side of the abdomen. A RUMI (CooperSurgical, Trumbull, CT) uterine manipulator was placed into the uterine cavity. Laparoscopy showed no adhesions in the upper and mid-abdomen. The appendix and the intestines looked normal. Both the ovaries and fallopian tubes were normal. Uterine insufflation with methylene blue showed that both tubes were patent. There was dense endometriosis between the bladder and fundus of the uterus. The omentum was also adherent to the site of the endometriosis. There were endometriotic nodules on the left uterosacral ligaments and the peritoneum in the wall in the pouch of Douglas. The omentum was released, and laparoscopic adhesiolysis was performed. Both the paravesical spaces lateral to the nodule were dissected out. The bladder was released from the uterus with some difficulty. The peritoneal endometriosis in the Pouch of Douglas and the nodules in the left uterosacral ligament were excised. Cystoscopy was performed and stents were first placed in both ureters. The nodule was found to be in the central position, and the margins were about 2 cm from both the ureteral orifices. The nodule was seen protruding into the bladder containing bluish lesions. Demarcation of the bladder endometriosis was done using a resectoscope. Using a needle electrode, a deep circular incision was made around the bladder nodule and into the detrusor muscle. Cystoscopic perforation of the bladder was done and was seen laparoscopically. The bladder endometriotic nodule was completely excised laparoscopically after the demarcation line created via the cystoscopy. Stay sutures were first placed at the superior and inferior edges of the defect. The bladder was repaired continuously in 1 layer using polyglactin 3-0 sutures. The nodule was placed in a bag cut into smaller pieces and removed through the umbilical incision. At the end of the surgery a cystoscopy was perform to check the integrity of the suture. The pelvis was then washed. A bladder catheter was placed. The trocars were then removed under vision, and the rectus sheath was closed using polyglactin 1 suture. The skin incisions were closed. The operation time was 2 hours. The patient received antibiotics for 10 days. She was discharged with a catheter in place on day 3. She underwent a cystogram on day 10 of the surgery, and the bladder was found to be intact. The catheter was then removed. She was seen 6 weeks after the surgery and was well without any symptoms. The ureteric catheters were removed. Histopathology confirmed bladder endometriosis. Five months later she conceived spontaneously and delivered her third child naturally in June 2017. She was seen after her delivery and was advised to take oral contraceptive pills continuously or an intrauterine contraceptive device to prevent recurrence of the endometriosis. She took the oral contraceptive pills for 3 months and then refused any further treatment. She was last seen in February 2019 and was well without any symptoms., Conclusion: In bladder endometriosis a combined approach with the urologist can assist in safely excising deep bladder endometriosis without removal of normal bladder tissue. Stents placed in the ureter assist in avoiding injury to the ureters. Demarcating the endometriotic nodule by the urologist through the bladder and excising the bladder nodule laparoscopically is both safe and effective., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Aim: This study was undertaken to determine the incidence and patterns of malignancies in rheumatoid arthritis (RA) patients in our cohort., Methods: Between 2001 and 2013, we analyzed 1117 patients in the prospective Tan Tock Seng Hospital (TTSH) RA Registry. Patients who developed malignancies after the onset of RA were identified from this registry. Age- and sex-adjusted standardized incidence ratios (SIRs) were calculated to compare observed to expected numbers of malignancies based on data from the Singapore Cancer Registry., Results: Out of 19 839 person-years of follow-up, 132 incident malignancies were diagnosed during the observation period. There were 114 (86.4%) solid-organ tumors and 18 (13.6%) hematological malignancies. The SIR (95% confidence interval) for all malignancies combined was 1.28 (0.88-1.87) for males and 1.21 (1.00-1.46) for females. Compared to the general population, we found a 4- to 5-fold increase in lymphoma among our RA patients compared to the general population (SIR 5.05 [1.90-13.46] for males and 3.75 [1.95-7.20] for females). The SIR of lung malignancy in male RA patients is 2.36 (1.23-4.53) and SIR of cervical malignancy in female RA patients is 3.72 (2.20-6.23)., Conclusion: There is a trend toward an overall increased malignancy risk in our RA patients compared to the general population. Specifically, there is an increased risk of lymphomas in all RA patients, lung malignancy in male patients, and cervical malignancy in female patients, compared to the general population., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti-BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM-R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti-dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM-R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity (r = -0·436, P < 0·01), levels of anti-dsDNA antibody (r = -0·347, P < 0·02) and BAFF (r = -0·459, P < 0·01). The majority of patients in this multi-ethnic Asian SLE cohort had elevated levels of BAFF and anti-BAFF antibodies. Anti-BAFF autoantibody levels correlated negatively with clinical disease activity, anti-dsDNA and BAFF levels, suggesting that they may be disease-modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti-cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti-cytokine therapies., (© 2017 British Society for Immunology.)

Studies have shown that the genetic risk factors for rheumatoid arthritis (RA) differ substantially between Asian and Caucasian populations. Even among Asian populations, the genetic contributions of NLRP1, PTPN22 and PADI4 have been controversial. Consequently, we sought to address these separate findings and determine whether any of these proposed risk variants are associated with RA susceptibility, onset, DAS activity and erosion in a Singaporean Chinese cohort. We genotyped five SNPs within NLRP1 (rs878329 and rs6502867), PTPN22 (rs2488457 and rs6665194), and PADI4 (rs2240340) in 500 anti-cyclic citrullinated peptide antibody-positive (ACPA) patients with RA and 500 healthy controls using TaqMan assays. The CC genotype of NLRP1 rs878329 and TT genotype of PADI4 rs2240340 were associated with RA susceptibility. The risk association of the T allele of PADI4 rs2240340 with RA was confirmed through a meta-analysis based on previous reports in Asian populations. The GG genotype of PTPN22 rs6665194 (-3508A>G) was associated with significantly reduced risk of RA. No significant association was found for NLRP1 rs6502867 T/C and PTPN22 rs2488457 G/C polymorphisms. None of the five SNPs was associated with RA's clinical features. This work supports the association of the T allele of PADI4 rs2240340 with RA in Asians. The roles of NLRP1 rs878329 G/C and PTPN22 rs6665194 A/G polymorphisms were demonstrated for the first time. We also propose rs6665194 to be a promising candidate for RA risk evaluation between ethnicities.

Objective: To describe the demographic characteristics, clinical features, functional status and quality of life of elderly-onset (EORA) and young-onset (YORA) rheumatoid arthritis (RA) patients in an Asian cohort., Methods: We studied all RA patients in our prospective disease registry, utilizing baseline data. EORA was defined as disease onset at 60 years or older. We collected data from January 2001 to December 2012., Results: There were 1206 patients in our cohort, of which 178 (14.8%) had EORA, with a mean age of onset of 66.7 ± 5.6 years. There were more males in the EORA than YORA group (23.0% vs. 14.7%, P = 0.005). EORA patients were diagnosed sooner after symptom onset and had a higher number of comorbidities (median 2 [inter-quartile range 1-3] vs. 1 (0-2), P < 0.001). They were less likely to be rheumatoid factor positive, had higher erythrocyte sedimentation rate values and lower hemoglobin concentrations. There was no significant difference in joint counts, Disease Activity Score of 28 joints activity score and prevalence of radiographic erosions. Though EORA patients had worse Health Assessment Questionnaire scores and poorer functional status than YORA ones, they had lower pain scores and higher scores in the general health and mental component summary of the Short Form-36. EORA patients received significantly lower numbers of disease-modifying anti-rheumatic drugs., Conclusions: EORA and YORA patients had different demographic characteristics. Although they had similar disease activities, EORA patients received less intensive treatment. EORA patients had a higher number of RA-related co-morbidities and poorer physical functioning but they coped better emotionally and mentally., (© 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)