Background Traditional risk factors do not fully explain the increased risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). [1] The Hp2-2 genotype is known to confer a lower anti-oxidant and higher inflammation effect when compared to the non Hp2-2 genotype. [2] Objectives This study aims to investigate the association of Hp genotype with CVD in patients with RA. Methods Sixty-nine with CVD cases and 207 gender and ethnicity matched control (without CVD) with allocation of 1:3, were retrieved from the Tan Tock Seng Hospital RA registry from 1 Jan 2000 to 31 Dec 2020. Hp genotype was determined using TaqMan-based real-time polymerase chain reaction (PCR). CVD was examined against demographics, clinical and laboratory variables in univariate models. Associations between Hp genotypes and CVD were analyzed using conditional logistic regression. All analysis was done using Stata version 16.1. Results The prevalence of Hp2-2 genotype was: Group 1 (CVD group): Chinese: 29/57, 50.9%, Indian: 5/5, 100%, and Malay 2/7, 28.6%; Group 2 (Control group): Chinese 80/171, 46.8%, Indian: 10/15, 66.7%, and Malay 11/21, 52.4%). CVD was significantly associated with age, disease duration, disease activity score 28 (DAS28), diabetes, hypertension, hyperlipidemia, Hp 2-2 allele, rheumatoid factor, cyclic citrullinated peptide (CCP), cumulative dose of prednisolone and methotrexate. Hp 2-2 genotype significantly associated with CVD outcomes in the logistic regression model adjusting for age, smoking status, DAS28, diabetes, hypertension, hyperlipidemia, and CCP (adjusted matched odds ratio: 1.13 (95% CI: 1.01 – 1.27); p = 0.033). Conclusion The Hp 2-2 genotype is associated with an increased risk of CVD in patients with RA in the Singapore multi-ethnic Asian cohort. Further epidemiological and mechanistic studies are warranted to understand the role of the Hp-genotype in rheumatoid arthritis. References [1] Agca R, Heslinga SC, Rollefstad S, Heslinga M, McInnes IB, Peters MJL, et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Annals of the Rheumatic Diseases. 2017;76(1):17-28. [2] Costacou T, Levy AP. Haptoglobin Genotype and Its Role in Diabetic Cardiovascular Disease. Journal of Cardiovascular Translational Research. 2012;5(4):423-35. Acknowledgements We thank Ms Amelia Lim Qiu Ru, and Ms Choong Ying Qi for the assistance with data collection. This work is supported by Tan Tock Seng Hospital FY2021 Pitch-for-Fund Program Grant (Grant ID: PFFP 21-08). Disclosure of Interests None Declared.
IntroductionTraditional risk factors do not fully explain the increased risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). The Haptoglobin (Hp) 2-2 genotype confers a lower anti-oxidant and higher inflammatory effect on the vasculature compared to the non-Hp 2-2 genotype. This study investigates the association of the Hp genotype with CVD in patients with RA.MethodsData from 69 RA patients with CVD and 207 sex- and ethnicity-matched RA patients without CVD, collected from 1 January 2000 to 31 December 2020, were retrieved from the Tan Tock Seng Hospital RA Registry. CVD was examined against demographics, clinical and laboratory variables in univariate models. Associations between the Hp genotypes and CVD were analyzed using conditional logistic regression.ResultsWe studied 276 patients (65.2% female, 82.6% Chinese, median age 60.9 years). Most participants were in low disease activity or remission (79.3%). The Hp 2-2 genotype was present in 49.6% (137/276). In the group with CVD, the prevalence of the Hp 2-2 genotype was 50.9% (29/57) in the Chinese, 100% (5/5) in the Indians, and 28.6% (2/7) in the Malays. In the non-CVD group, the respective prevalence was 46.8% (80/171), 66.7% (10/15), and 52.4% (11/21). In univariate analysis, the matched odds ratio (OR) of the Hp 2-2 genotype for CVD in RA was 1.34 [95% confidence interval (CI): 1.22–1.47; p < 0.001]. The Hp 2-2 genotype was significantly associated with CVD (adjusted matched OR: 1.13; 95% CI: 1.01–1.27; p = 0.033) in the multivariate logistic regression model after adjusting the confounding factors, including age, smoking, diabetes, hypertension, hyperlipidemia, anti-CCP autoantibodies, and disease activity.ConclusionThe Hp 2-2 genotype is associated with an increased risk of CVD in patients with RA in this multi-ethnic cohort.
Background: Both diabetes mellitus (DM) and rheumatoid arthritis (RA) are prevalent diseases and represent the leading causes of disability and mortality worldwide. Systemic chronic inflammation is recognized as the underlying etiology of a variety of diseases, including DM and RA [1]. Additionally, cardiovascular and musculoskeletal complications from DM may influence the outcomes of RA patients. Objectives: To investigate the impact of DM on outcomes of RA patients. Methods: This is a cross-sectional study including 583 RA patients with 5 years’ history after diagnosis in Tan Tock Seng Hospital RA registry, Singapore from 2001 to 2013. Information related to demographics, serologies, clinical features, comorbidities, and outcomes was collected. Independent t-test or Mann-Whitney U test was used to compare continuous quantitative data, while Pearson Chi-square or Fisher Exact test for categorical data. With adjustment for age, gender, ethnicity, smoking and comorbidities, multivariate regressions were performed to analyze the impact of DM on outcomes of RA patients. Results: DM is more prevalent in Malay and Indian patients than Chinese patients with RA (26%, 24% and 11% respectively, p = 0.005). There is no difference of disease activity between DM and non DM patients. There is a tendency that non diabetic RA patients use more methotrexate ( p = 0.052) and leflunomide ( p = 0.058). Diabetic RA patients are in higher risk of poor American College of Rheumatology (ACR) functional status ( p = 0.009), knee arthroplasty ( p < 0.001) and admissions ( p = 0.006). Adjusted for age, gender, ethnicity, smoking and comorbidities, multivariate regression analyses showed a trend of poor function status for diabetic RA patients, i.e. ACR functional status (adjusted odds ratio [aOR]: 1.802, 95% confidence interval [CI]: 0.968 – 3.353, p = 0.063) and median Health Assessment Questionnaire (HAQ) (β coefficient value: 0.129, 95% CI: -0.010 – 0.267, p = 0.068), and higher risk for knee arthroplasty for diabetic RA patients (aOR: 3.480, 95% CI: 1.016 – 11.920, p = 0.047). Conclusion: This is the first report on the impact of DM on RA outcomes in a long term follow-up RA registry in a multiethnic Asian society. References: [1]Furman, D., Campisi, J., Verdin, E. et al. Chronic inflammation in the etiology of disease across the life span. Nat Med 25, 1822–1832 (2019). Acknowledgments: TTSH Rheumatoid Arthritis Study Group Disclosure of Interests: None declared
Background Response to disease-modifying antirheumatic drugs (DMARDs) is heterogenous. Clinical information and baseline characteristics do not allow reliable prediction of which trajectory patients will follow after DMARD initiation. Objectives We analysed the change in disease activity over the first two years of treatment in rheumatoid arthritis (RA) to identify different treatment response patterns among RA patients initiating DMARDs. We wanted to establish a predictive model for identifying patients with different treatment response patterns. Methods We selected patients from our prospective RA disease registry who have been treated for three months or fewer at study entry. We analysed the change of the disease activity, as defined by the DAS28–ESR, over the subsequent two years. A predictive model with parameters from three time points is proposed to stratify patients according to the outcomes.Abstract AB0214 – Figure 1 Results We analysed the data from 179 patients over 1044 study visits. We discerned three groups of patients according to disease activity trajectories:1the first group (53%) has high DAS at study entry and approach remission after 18 months;2the second group (22%) has high DAS at entry that remained elevated throughout the study period; and,3the third group of patients (25%) started with moderately high DAS and reached remission after 3 months of treatment. Patients at risk of being in the third group can be identified using data from three time points, at initiation of DMARDs, at 3 months and at 6 months. Conclusions RA patients showed three distinct disease activity trajectories with treatment. Our model can categorise patients into these groups. References [1] Aga Ab, et al. Time trends in disease activity, response and remission rates in rheumatoid arthritis during the past decade: results from the NOR-DMARD study 2000–2010. Ann Rheum Dis2015;381–8. [2] Courvoisier DS, et al. Rheumatoid arthritis patients after initiation of a new biologic agent: trajectories of disease activity in a large multinational cohort study. EBioMedicine 2016;302–306. [3] Siemons L, Ten Klooster PM, Vonkeman HE, Glas CAW, Van de Laar MAF. J. Distinct trajectories of disease activity over the first year in early rheumatoid arthritis patients following a treat to-target strategy. Arthritis Care Res2014;66:625–630. [4] Aga Ab, et al. Time trends in disease activity, response and remission rates in rheumatoid arthritis during the past decade: results from the NOR-DMARD study 2000–2010. Ann Rheum Dis 2015,381–8 [5] Courvoisier DS, et al. Rheumatoid arthritis patients after initiation of a new biologic agent: trajectories of disease activity in a large multinational cohort study. EBioMedicine 2016,302–306 [6] Siemons, L., Ten Klooster, P. M., Vonkeman, H. E., Glas, C. A. W. & Van de Laar, M. a F. J. Distinct trajectories of disease activity over the first year in early rheumatoid arthritis patients following a treat to-target strategy. Arthritis Care Res.66, 625–630(2014) Disclosure of Interest None declared
Background Rheumatoid arthritis (RA) is a fairly common inflammatory autoimmune disease with a prevalence of 1% to 1.5%. Patients experience chroic joint pain, swelling and overtime irreversible joint damage. Genetic variants known to contribute to rheumatoid arthritis (RA) susceptibility have been reported in more than 120 genes, including the HLA, PTPN22, CTLA4, TNFAIP3, PADI4, FCRL3, CD4, CD244 and CD40. The genetic susceptibility to RA has not been studied in the Singapore population. Objectives To identify novel risk variants in candidate genes previousy reported to be associated with rheumatoid arthritis (RA) in Singapore Chinese RA patients positive for anti-citrullinated peptide antibodies (ACPA). Methods All the 128 known candidate genes associated with RA identified through GWAS were sequenced in 48 RA patients and 45 controls. The resultant data was analysed for association using single variant association and pathway-based association enrichment tests. In addition, the genetic burden due to rare variants was assessed using the C-alpha test. The candidate variants that showed significant association were validated in a larger cohort of 500 RA cases and 500 controls using mass array and Taqman technologies. Results 39 variants in 18 genes were identified using single variant association analysis and C-alpha test. IL6ST, with stepwise filtering. Among these, the missense variant in IL6ST, 5:55260065 (p.Cys47Phe) was significantly associated with RA in the Singapore Chinese patients (p=0.0194). The insignificant results of additional potential rare variants such as IL6ST, 5:55237103 and PXK rs199881366 is highly due to the limitations of our small sample size. Conclusions Our results suggest that IL6ST, 5:55260065, 5:55237103 and PXK rs199881366 confer risk of RA in ACPA-positive Chinese patients. Disclosure of Interest None declared
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<001], which were correlated positively with anti-dsDNA antibody levels (r=0253, P<003), and SLAM-R scores (r=0627, P<001). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity (r=-0436, P<001), levels of anti-dsDNA antibody (r=-0347, P<002) and BAFF (r=-0459, P<001). 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.
Objectives Patients with rheumatoid arthritis (RA) have been shown to have an increased risk of developing malignancies. This study was undertaken to determine the incidence and patterns of malignancy in RA patients and identify risk factors of malignancy among patients with RA. Methods Patients from the TTSH RA Registry were followed up longitudinally and those who developed malignancies from 2001 to 2013 after the onset of RA were identified. Age-standardised rates (ASRs) of various cancers were analyzed and compared with the Singapore Cancer Registry data. Risk factors for developing malignancy, including demographics and disease characteristics at baseline, were analyzed using Chi-squared test and student9s t test. Results Of the 1,134 patients in the registry, 28 patients were excluded as they developed malignancy prior to study enrollment. 1,106 patients were included in the final analysis. Of the 1,106 patients, 81 patients developed malignancies at a mean interval of 15.1 (SD 9.7) years after the onset of RA. The mean age of the 81 patients was 65.9 (SD 10.8) years, of which 61 (75.31%) were females and 69 (85.19%) were Chinese. There were 70 (86.4%) with solid-organ tumours and 11 (13.6%) haematological malignancies. The ASR of cancer in RA patients was 310.3 for males and 232.5 for females per 100,000 person-years, compared with 229.3 (95%CI 226.5–232) for males and 218.3 (95%CI 213.8–216.3) for females in the general population. By cancer type, there is an increased risk of lung cancer, lymphoid neoplasms and stomach cancer in RA compared with the general population. The risks factors for developing malignancy (p<0.05) include male gender, non-Indian ethnicity, onset of RA at an older age, untreated RA and higher disease activity. Conclusions The incidence of solid-organ malignancies was higher than hematological malignancies, unlike that in the literature. The overall risk of malignancy is higher in RA patients. Chronic inflammation from RA is associated with increased risk of malignancy. Acknowledgement This study is supported by the Centre Grant, National Medical Research Council, Ministry of Health, NMRC/CG/017/2013. Disclosure of Interest None declared
Background The application of statistical clustering methods to various clinical datasets has revealed unexpected patterns of disease that may have practical implications. There are advantages to categorising patients with rheumatoid arthritis (RA) into distinct subsets for treatment and prognostication. Objectives To examine the cluster pattern of joint deformity of an inception cohort of RA patients. Methods All patients fulfilled the 1987 ACR criteria for RA, had ≤2 years disease duration at recruitment and were followed up from enrolment till 2014. Correlation of joint deformity symptoms at last study visit among the eight joints were analysed using eigen vectors from principal component analysis. K-means clustering analysis was applied to classify the RA patient subgroups based on distribution of joint deformity involvement. Joint deformity pattern was analysed at the last visit and correlated with socioeconomic, extra-articular features (EAF), DAS28 and HAQ scores, rheumatoid factor (RF), anti-citrullinated peptide antibody (ACPA) status and treatment. Results The mean age of the RA cohort was 50.4 years, 75.5% were Chinese and mean follow-up period was 88.4 months. Correlation analysis showed that the joint deformity involvement could be classified into three categories: proximal interphalangeal/metacarpophalangeal joint (PIP/MCP), shoulder/elbow/ankle (S/E/A) and wrist/knee/metatasophalangeal (W/K/MTP). Cluster analysis showed four patterns of joint deformity: mild involvement of PIP/MCP joints (group I), dominant involvement of S/E/A and W/K/MTP (group II), W/K/MTP involvement (group III) and dominant PIP/MCP/S/E/A/W/K/MTP involvement (group IV). There was no significant difference in mean age, disease duration, work status, occupation, smoking status, prevalence of RF and ACPA, DAS28 and HAQ scores among the four groups. Group IV patients had a significantly longer symptom duration prior to diagnosis, received higher number of non-biologic DMARDs and were more likely to have radiographic erosions (p<0.05). Unlike other joints, wrist deformity was significantly correlated with prior wrist tenderness or swelling (34.5% of patients). Conclusions Cluster analysis showed four subgroups of RA patients based on pattern of joint deformity. The presence of wrist synovitis at baseline may predict wrist deformity. Factors other than socioeconomic, RF, ACPA need to be explored to explain the clustering of joint deformity in our inception cohort. Acknowledgements We thank Ms Safiyya Mohamed Ali for her kind assistance. Disclosure of Interest None declared
Objectives To identify predictors of orthopaedic surgery and its impact on quality of life in a South-East Asian rheumatoid arthritis registry cohort. Methods Data was collected from patients enrolled in the Tan Tock Seng Hospital Rheumatoid Arthritis Registry. All patients fulfilled the 1987 ACR criteria for RA. The clinical, extraarticular features (EAF), disease activity score (DAS 28), functional status (Health Assessment Questionnaire, HAQ) and health- related quality of life measures (SF-36) were prospectively collected since 2001. Comparison between those with and without orthopaedic surgical procedures (groups I and II respectively) at entry to the registry till 2013 or death was done. Risk factors for surgery at study entry were determined using logistic regression (STATA SE 10), adjusted for age and disease duration. Results The study comprised of 1049 patients, predominately Chinese (77.9%); 190 patients (18.1%) had surgery (synovectomy 6.4%, arthroplasty 17.5%, arthodesis 1.1%). The mean age of groups I and II were similar (49.2 vs 48.2 years, p=0.35), mean duration from onset of RA to 1st joint surgery was 136.2 months. Group I had significantly longer symptoms before seeking rheumatologists (mean 63.5 vs 32.0 months, p<0.0001), duration from onset of RA to 1st disease modifying drug (74.2 vs 39.3 months, P<0.0001) and disease duration (243.1 vs 151.6 months, p<0.0001). Higher deformed joint count (mean 4.8 vs 1.7, OR 1.13, p<0.001), presence of radiographic erosions (70.4 vs 52.3%, OR 1.46, p<0.05), EAF (36.3 vs 24.1%, OR 1.67, p=0.004), HAQ score >1.5 (15.4 vs 7.5%, OR 3.08, p<0.001 and not DAS 28 or RF positivity were predictive of orthopaedic surgery. Lower scores were seen for the physical functioning domains of the SF36 in the group that had orthopaedic surgery, but there was no significant difference in the mental component between the two groups. Conclusions Delayed diagnosis and delay in initiation of disease modifying therapy were positive predictors of orthopaedic surgery in our cohort of RA patients, independent of disease activity scores and rheumatoid factor positivity. RA patients in this cohort who required orthopaedic intervention report significantly poorer scores on physical quality of life measures. Acknowledgements This study is supported by the Centre Grant, National Medical Research Council, Ministry of Health, Singapore. (CG12Aug17) Disclosure of Interest None declared
Background Various generic quality-of-life QoL (QoL) scales such as MOS 36-Item Short-Form Health Survey (SF-36) and disease-specific ones such as systemic lupus erythematosus QoL (SLEQOL) have been used to study the QoL of lupus patients. Most of the studies are cross-sectional and, consequently, information about the responsiveness of such instruments is scant. Objectives We studied the responsiveness of SLEQOL and SF-36 in lupus patient as they receive new drug treatment. Methods We selected patients from our prospective SLE registry who were prescribed new medications. We studied the differences in the QoL at study visits just before and just after the introduction of azathioprine, oral cyclophosphamide, intravenous cyclophosphamide, danazol, cyclosporine A, mycophenolate or hydroxychloroquine in an intention-to-treat manner. We collected clinical data and scores from SF-36, SLEQOL, Rheumatology Attitudes Index (RAI), SLE Disease Activity Index (SLEDAI) and revised Systemic Lupus Activity Measure (SLAM-R). Results There were 216 SLE patients (with 194 females) with 303 new drug initiations. The mean age was 36.23 ± 11.78 years. The mean age of diagnosis was 27.65 ± 10.34 years. Using SLEQOL, we found that the use of IV cyclophosphamide, mycophenolate and azathioprine is associated with significant improvements in QoL, in contrast to oral cyclophosphamide, cyclosporin A, danazol and hydroxychloroquine. IV cyclophosphamide is associated with improvement in the physical functioning, activities and self-image domains of SLEQOL, mycophenolate in the treatment and self-image domains and azathioprine in the activities and mood domains. SF-36 reflected QoL change with the use of IV cyclophosphamide (general health domain) and mycophenolate (physical functioning and role physical). Conclusions SLEQOL is responsive to the changes in QoL of SLE patients as they receive new medications. It distinguishes the differential effects on QoL of the various drugs. Different domains of the SLEQOL and SF-36 improved with the various medications. SLEQOL may be useful as an outcome measure in SLE clinical trials. Disclosure of Interest None Declared
Background There is little data on work disability in Asian patients with SLE. Loss of work ability contributes to loss in productivity, increase in health care cost and also loss of self esteem which in turn can lead to anxiety and depression. Objectives To determine the employment status, prevalence of work disability in a cohort of Asian SLE patients and to identify its predictors. Methods We established our SLE registry in 2001. This follows about 1000 patients who are followed up according to a standard protocol by trained staff rheumatologists or trainees at regular 4-12 months. A cross-sectional questionnaire study was performed to evaluate the employment status of consecutive patients with SLE. The following parameters were collected: demographic, socioeconomic data, employment status including their history of having modified their job or having changed their job(s) and disease characteristics. Work disability was defined as failure to work due to SLE activity and its related complications. Results 323 patients were surveyed (mean age 45.5±12.1years, 92.4% women, 90% of Chinese descent, mean SLE duration 15.8±11.1years). Majority were married (65.8%) and 82.8% earned below the median Singapore income of $5000 per month (2010 census) More than half the patients (55.3%) did not have health insurance. There were 62 patients who were not in the workforce at time of questionnaire (30 housewives, 31 student, 1 retiree) and hence were excluded. Of the 261 who were in the workforce, 78((29.9%) lost their working ability. 52 of these patients (67.1%) reported they stopped work earlier than they had wanted to. The self reported causes of inability to work were fatigue (43.9%) and joint pains or aches (36.8%). A significant number of patients who were work disabled also modified their work or had to change jobs. Of the 78 patients who were unable to work, 47/78 (60%) modified their jobs by doing lighter duties (36.4%), or doing fewer hours or going part time (41.9%). Thirty one patients (39.7%) also changed jobs prior to stopping work with 60.5% of patients having changed 2 jobs. Conclusions Work disability is an important problem among SLE patients. The unemployment rate is high compared to the national unemployment rate of 2.2%. Majority of the the patients who were work disabled experienced a period of work instability before they stopped work. Disclosure of Interest None Declared
Patients with systemic lupus erythematosus often assess their disease activity differently from their physicians. We studied the factors associated with this discordance. The data provided by 534 systemic lupus erythematosus patients were analyzed. We compared the physician and patient assessments of lupus activity on a visual-assessment scale from the same visit. We collected clinical data and scores from MOS 36-Item Short-Form Health Survey, Systemic Lupus Erythematosus Quality-of-Life Questionnaire, Rheumatology Attitudes Index, Systemic Lupus Erythematosus Disease Activity Index, and revised Systemic Lupus Activity Measure. Patients tended to score their disease activity higher than do their physicians, when these factors were present: poorer general health assessment, presence of thrombocytopenia, hypertension and urinary sediments, and difficulty in carrying groceries. Physicians tended to score the disease activity higher than do the patients in these circumstances proteinuria, hemolysis, use of azathioprine or cyclophosphamide, tiredness, photosensitivity, higher revised Systemic Lupus Activity Measure score, casturia, and patient report of being more easily ill than are other patients. There was only moderate correlation between the discordance in the baseline and the subsequent visits. The physician assessment of disease activity at baseline correlated better with an objective measure of disease activity (revised Systemic Lupus Activity Measure) in the subsequent visit than the patient assessment. In conclusion, discordance in the perception of disease activity between patients and physicians may be amenable to intervention.
Our objective was to investigate the serum levels of interferon-inducible protein-10 (IP-10) in systemic lupus erythematosus (SLE) and their correlation with disease activity and organ manifestations. Serum IP-10 levels were assessed in 464 SLE patients and 50 healthy donors. Disease activity was assessed by the revised SLE Activity Measure, and the concomitant active organ manifestations, anti-ds DNA antibody titres, complement levels and erythrocyte sedimentation rates recorded. Peripheral blood mononuclear cell (PBMC) synthesis of IP-10 in SLE patients and controls was determined by in vitro cultures stimulated with mitogen or lipopolysaccharide. Elevated serum IP-10 levels were observed in SLE patients, which were significantly higher in the presence of active haematological and mucocutaneous manifestations. SLE PBMCs exhibited enhanced spontaneous IP-10 production in vitro. Serial IP-10 levels correlated with longitudinal change in SLE activity, even at low levels where anti-dsDNA antibody and complement levels remain unchanged. These data demonstrate that IP-10 levels are increased in SLE and serum IP-10 may represent a more sensitive marker for monitoring disease activity than standard serological tests.
OBJECTIVETo assess the reliability, validity and sensitivity to change of a Chinese version of the 36-item Short-Form Health Survey (SF-36) in Chinese-speaking patients with rheumatoid arthritis (RA) in Singapore.METHODSThe psychometric properties of the Chinese Hong Kong standard version of the SF-36 were assessed in 401 RA patients. The construct validity of the Chinese SF-36 was assessed by comparison with the American College of Rheumatology (ACR) functional status, a validated Chinese Health Assessment Questionnaire (C-HAQ) and markers of RA activity and severity.RESULTSThe overall Cronbach's coefficient alpha was 0.921, reflecting excellent internal consistency. The instrument showed reasonable test-retest reliability except in the social functioning (SF) subscale. There was a significant ceiling effect in the role physical (RP), SF and role emotional (RE) subscales and a floor effect in the RP and RE subscales. Physical function (PF) and SF were strongly correlated with C-HAQ and patient's assessment of RA activity [Pearson's correlation coefficient (r) ranging from -0.41 to -0.53] and moderately correlated with ACR functional status (r = -0.35 and -0.3, respectively). Weak correlations were also found between the Chinese SF-36 and markers of RA activity, deformed joint count and radiographic damage. PF and SF were the subscales most responsive to change in quality of life (QOL).CONCLUSIONThe Chinese SF-36 showed reasonable reliability, criterion validity and responsiveness with limitations in certain subscales. Overall, the physical domains and PF in particular may be the most ideal psychometric measures of QOL in RA.