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Objective: The ACR-EULAR Myositis Response Criteria (MRC) were developed as a composite measure using absolute percentage change in six core set measures (CSMs). We aimed to further validate the MRC by assessing the contribution of each CSM, frequency of strength vs extramuscular activity improvement, representation of patient-reported outcome measures (PROM), and frequency of CSM worsening., Methods: Data from adult dermatomyositis/polymyositis patients in the rituximab (n = 147), etanercept (n = 14), and abatacept (n = 19) trials, and consensus patient profiles (n = 232) were evaluated. The Total Improvement Score (TIS), number of improving vs worsening CSMs, frequency of improvement with and without muscle-related CSMs, and contribution of PROM were evaluated by MRC category. Regression analysis was performed to assess contribution of each CSM to the MRC., Results: Of 412 adults with dermatomyositis/polymyositis, there were 37%, 24%, 25%, and 14% with no, minimal, moderate, and major MRC improvement, respectively. The number of improving CSMs and absolute percentage change in all CSMs increased by improvement category. In minimal-moderate improvement, only physician-reported disease activity contributed significantly more than expected by MRC. Of patients with at least minimal improvement, 95% had improvement in muscle-related measures and a majority (84%) had improvement in PROM. Patients with minimal improvement had worsening in a median of 1 CSM, and most patients with moderate-major improvement had no worsening CSMs. Physician assessment of change generally agreed with MRC improvement categories., Conclusion: The ACR-EULAR MRC performs consistently across multiple studies, further supporting its use as an efficacy end point in future myositis therapeutic trials., (Published by Oxford University Press on behalf of the British Society for Rheumatology 2023.)

Objectives: To investigate longitudinal changes of the EULAR SS Patient-Reported Index (ESSPRI) and EULAR SS Disease Activity Index (ESSDAI), and identify factors associated with patient acceptable symptom state (PASS) in patients with primary SS (pSS)., Methods: We assessed ESSPRI, ESSDAI, clinical ESSDAI (ClinESSDAI), EULAR Sicca Score, EuroQoL 5-dimension (EQ-5D), Fatigue Severity Score, Beck Depression Inventory, and patient global assessment (PGA) for pSS, and visual analogue scale (VAS) scores for glandular and extra-glandular symptoms at baseline and follow-up. The responses to the currently available standards of care were evaluated by the PASS, the minimal clinically important improvement (MCII) of ESSPRI and ESSDAI, and a modified SS Responder Index-30 (mSSRI-30) response., Results: Among 115 patients enrolled, 102 (88.7%) completed a median 3-year follow-up. The ESSPRI, ClinESSDAI and EQ-5D levels remained stable, although the PGA and ESSDAI significantly improved (both P <0.05). Of the 102 patients, 52 (51.0%) patients achieved the PASS at the follow-up and tended to attain the ESSPRI-MCII and mSSRI-30 (both P < 0.001) more frequently than the non-PASS group. Multivariate analysis revealed that the PASS was significantly associated with baseline ESSPRI negatively [odds ratio (OR) 0.609] and ESSDAI positively (OR 1.224). When categorized using baseline ESSPRI and ESSDAI, a subgroup of low ESSPRI and high ESSDAI reached a PASS achievement rate of 79.3%., Conclusion: Although longitudinal changes in ESSPRI and ClinESSDAI are stable in pSS, baseline ESSPRI and ESSDAI could provide prognostic information on the subsequent achievement of PASS, using currently available treatments. A categorization model using ESSPRI and ESSDAI may have clinical implications., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: We aimed to compare tuberculosis (TB) risk during biologics treatment between patients with RA who did (prophylaxis) and did not (non-prophylaxis) undergo chemoprophylaxis following pre-biologic latent TB screening in Korea of an intermediate TB burden., Methods: Using the 2002-16 Korea National Health Insurance database, we conducted a cohort study examining TB risk, defined by International Classification of Diseases Tenth Revision codes plus anti-TB drugs, among RA patients initiating a biologic drug with and without chemoprophylaxis after screening triage for latent TB. To control baseline confounding, we used propensity score-based fine stratification (PSS) and weighting. Cox proportional hazards models estimated hazard ratios and 95% CIs comparing TB risk between the prophylaxis vs non-prophylaxis groups., Results: The PSS-weighted study cohort (mean age 57.0 years; 81.3% female) included 2249 and 7225 RA patients in the prophylaxis and non-prophylaxis groups, respectively. During 2.42 years of biologics treatment, 118 patients developed TB with the incidence rate per 100 person-years of 0.33 in the prophylaxis and 0.63 in the non-prophylaxis groups. The PSS-weighted hazard ratio (95% CI) for TB associated with the prophylaxis was 0.52 (0.32, 0.86). During the follow-up time, the incidence rate of TB remained consistently low in the prophylaxis group but it was highest in the first year, then time-dependently declined in the non-prophylaxis group., Conclusion: This population-based cohort study warns that the current screening-based preventive strategy generates a substantially higher TB risk after biologics initiation among screening-negative patients compared with screening-positive patients receiving chemoprophylaxis, when the background TB burden is not low., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To compare cardiovascular (CV) risk among gout patients initiating allopurinol vs febuxostat., Methods: Using 2002-2015 Korean National Health Insurance Service data for the entire Korean population, we conducted a cohort study on gout patients initiating allopurinol or febuxostat. The primary outcome was a composite CV end point of myocardial infarction, stroke/transient ischaemic attack, or coronary revascularization. Secondary outcomes were individual components of the primary outcome, and all-cause mortality. We used propensity score-matching with a 4:1 ratio for allopurinol and febuxostat initiators to control for confounding. Competing risk analyses were done for non-fatal outcomes accounting for deaths., Results: We included 39 640 allopurinol initiators propensity score-matched on 9910 febuxostat initiators. The mean age was 59.1 years and 78.4% were male. The incidence rate per 100 person-years for the primary outcome was 1.89 for allopurinol and 1.84 for febuxostat initiators. The corresponding hazard ratio comparing allopurinol vs febuxostat initiators was 1.09 (95% CI: 0.90, 1.32). No significant difference was found for the secondary outcomes, including all-cause mortality (hazard ratio 0.96; 95% CI: 0.79, 1.16). Subgroup analyses limited to those at high CV risk and to equipotent-dose initiators (i.e. allopurinol ⩾300 mg/day vs febuxostat ⩾40 mg/day) showed similar results., Conclusion: Overall, this large Korean population-based study suggests no difference in the risk of non-fatal CV events and all-cause mortality between allopurinol and febuxostat initiators. These findings are consistent with the recent US Medicare population study, although the current study population consisted of younger Asians., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: We examined the association between socioeconomic status (SES) and comorbidity distribution among patients with RA., Methods: Information on comprehensive health status of 1088 RA patients (weighted n = 612 303) was obtained from the 2007-2015 Korea National Health and Nutrition Examination Survey database. SES components were household equivalence income, education and area of residence. To minimize confounding by age, patients were stratified by median age (63 years). Age-adjusted odds ratio (OR) with 95% confidence interval (95% CI) was estimated, comparing weighted prevalence of individual comorbidities between low and high SES groups in each age stratum., Results: Among RA patients aged <63 years (mean 49 years, 70% female), we observed age-adjusted associations of depression (OR 2.13, 95% CI 1.01, 4.53), depressive mood (OR 2.68, 95% CI 1.54, 4.65), suicide ideation (OR 3.01, 95% CI 1.79, 5.07), diabetes (OR 3.09, 95%CI 1.31, 7.29), obesity (OR 2.04, 95% CI 1.30, 3.20), hypertriglyceridemia (OR 2.36, 95% CI 1.28, 4.34) and osteoarthritis (OR 2.12, 95% CI 1.13, 3.99) with low income, of suicide ideation with low education (OR 2.25, 95% CI 1.14, 4.44), but no association of any comorbidities with area of residence. Unhealthy behavior patterns were comparable between low- and high-income groups but patients with low income reported a numerically higher rate of failed access to necessary healthcare services. We did not find any association between SES and comorbidities among those aged ⩾63 years (mean 72 years, 83% female)., Conclusion: Among Korean RA patients aged <63 years, socioeconomic inequalities of multiple comorbidities in mental, cardiometabolic and musculoskeletal systems were found., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study investigated the expression of proviral-integration site for Moloney murine leukaemia virus (PIM) -1 kinase in RA synovium and RA fibroblast-like synoviocytes (FLSs) along with its impact on RA-FLS aggressiveness., Methods: The expression of PIM kinases was assessed in synovial tissues by immunohistochemistry and double IF. After PIM-1 inhibition using either small-interfering RNA or the chemical inhibitor AZD1208, we performed proliferation and migration assays and measured the levels of MMPs and IL-6 released from RA-FLSs under stimulation with proinflammatory cytokines (TNF-α, S100A4 and IL-6/soluble IL-6 receptor). Additionally, PIM-1-associated downstream signalling pathways were analysed by immunoblotting., Results: Three isoforms of PIM kinases were immunodetected in the synovial tissues from patients with RA or OA. Specifically, PIM-1 and PIM-3 were upregulated in RA synovium and PIM-1 was expressed in T cells, macrophages and FLSs. Additionally, upon stimulation of RA-FLSs with TNF-α, S100A4 and IL-6/sIL-6R, PIM-1 and PIM-3, but not PIM-2, were significantly inducible. Moreover, PIM-1 knockdown or AZD1208 treatment significantly suppressed basal or cytokine-induced proliferation and migration of RA-FLS and the secretion of MMPs from stimulated RA-FLSs. PIM-1 knockdown significantly affected the phosphorylation levels of extracellular signal-regulated kinase and cAMP responsive element binding protein in RA-FLSs., Conclusion: PIM-1 was upregulated in RA synovial tissues and RA-FLSs and its inhibition significantly reduced the proliferation, migration and MMP production of RA-FLSs in vitro. These findings suggest PIM-1 as a novel regulator of the aggressive and invasive behaviour of RA-FLSs and indicate its potential as a target for RA treatment.

Objective: The importance of hypomethylation in SLE is well recognized; however, the significance of hypermethylation has not been well characterized. We screened hypermethylated marks in SLE and investigated their possible implications., Methods: DNA methylation marks were screened in SLE whole-blood DNA by microarray, and two marks ( CD3Z and VHL hypermethylations) were confirmed by a methylation single-base extension method in two independent ethnic cohorts consisting of 207 SLE patients and 151 controls. The correlation with clinical manifestations and the genetic influence on those epigenetic marks were analysed., Results: Two epigenetic marks, CD3Z and VHL hypermethylation, were significantly correlated with SLE: CD3Z hypermethylation (odds ratio = 7.76; P = 1.71 × 10 -13 ) and VHL hypermethylation (odds ratio = 3.77; P = 3.20 × 10 -8 ), and the increased CD3Z methylation was correlated with downregulation of the CD3ζ-chain in SLE T cells. In addition, less genetic influence on CD3Z methylation relative to VHL methylation was found in analyses of longitudinal and twin samples. Furthermore, a higher CD3Z methylation level was significantly correlated with a higher SLE disease activity index and more severe clinical manifestations, such as proteinuria, haemolytic anaemia and thrombocytopenia, whereas VHL hypermethylation was not., Conclusion: CD3Z hypermethylation is an SLE risk factor that can be modified by environmental factors and is associated with more severe SLE clinical manifestations, which are related to deranged T cell function by downregulating the CD3ζ-chain., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Objectives: To evaluate partial remission during treatment with infliximab (IFX) + naproxen (NPX) vs NPX alone in patients from the two subgroups of SpA and explore baseline predictors of partial remission., Methods: Infliximab as First Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial was a double-blind, randomised controlled trial of IFX in biologic-naïve patients with early, active axial SpA. Patients were randomised (2:1) to receive 28 weeks of treatment with i.v. IFX 5 mg/kg (weeks 0, 2, 6, 12, 18 and 24) + NPX 1000 mg/day or i.v. placebo (PBO) + NPX 1000 mg/day. The current post hoc analysis evaluated outcomes in patients who did or did not meet modified New York radiographic criteria for AS., Results: The analysis included 94 patients who met AS criteria and 56 with non-radiographic axial SpA (nr-axSpA). At week 28, Assessment of SpondyloArthritis international Society (ASAS) partial remission was greater with IFX + NPX than PBO + NPX for both the AS group (70.5 vs 33.3%, respectively) and the nr-axSpA group (50.0 vs 37.5%, respectively). A similar pattern occurred with several efficacy measures. Larger treatment effects occurred in the AS group than the nr-axSpA group, possibly due to baseline differences in disease characteristics. Multivariable analyses identified the type of treatment, age and HLA-B27 status as predictors of ASAS partial remission in the total study population. MRI sacroiliac joint scores were associated with partial remission during IFX + NPX treatment., Conclusion: Patients with AS had greater partial remission with IFX + NSAID than NSAID therapy alone; patients with nr-axSpA had a smaller treatment effect. Baseline disease characteristics and age were associated with partial remission with IFX therapy., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: The aim was to compare standardized incidence ratios (SIRs) of cancers temporally related and unrelated to active myositis in patients with myositis., Methods: Fifty-two cancer cases were identified in 281 myositis patients. SIRs of cancers having temporal overlap with the active phase of myositis [cancers concurrent with active myositis (CAM), n = 30] and cancers not having such temporal overlap [cancers non-concurrent with active myositis (CNM), n = 22] were compared in 281 patients., Results: Patients with CAM were older at diagnosis of myositis, had a greater tendency to be male, more frequent dysphagia and less frequent interstitial lung disease than patients with CNM. CAM SIR (95% CI) was 1.78 (1.19, 2.56) and CNM SIR 1.23 (0.75, 1.90). The peak SIR was observed in the seventh decade of life for CAM and in the third decade for CNM. When stratified by myositis-cancer intervals, CAM SIR was 9.94 (6.43, 14.67) within 1 year of myositis diagnosis, whereas no temporal relationship was found for CNM. Elevated SIRs were observed for oesophageal cancer [57.77 (11.91, 168.82)], non-Hodgkin's lymphoma [41.43 (13.45, 96.69)], adenocarcinoma of unknown primary origin [67.6 (18.42, 173.07]), lung cancer [7.27 (1.98, 18.61)] and ovarian cancer [19.15 (2.32, 69.17)] within 3 years of CAM diagnosis. The cancer stage at the time of diagnosis was more advanced in CAM than CNM (P < 0.001), with a correspondingly increased hazard ratio of mortality [4.3 (1.5, 12.7)] in patients with CAM vs CNM., Conclusion: A significantly elevated SIR was found for CAM, whereas there was a comparable SIR for CNM relative to the general population. Multiple types of cancers showed elevated SIRs among CAM, but none among CNM. Given that cancer stages in CAM were far advanced at diagnosis, mortality risk was greater in patients with CAM., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To develop a decision model to identify SSc-associated interstitial lung disease (ILD) patients who are eligible for watchful waiting at ILD diagnosis., Methods: One hundred and fifty-one SSc-ILD patients who received medical care at Seoul National University Hospital from 1986 to 2013 were enrolled in this retrospective cohort study. ILD was diagnosed by chest CT. Patients with and without immunosuppressive treatment were compared in terms of characteristics at ILD diagnosis to identify distinguishing variables. After multivariate analysis, a decision model for watchful waiting was formulated. Its validity was assessed by comparing the survival of patients whose management in real practice did and did not accord with the management recommended by the model., Results: The untreated group had better survival than the immunosuppressive treatment group (P = 0.0316, by log-rank test). The untreated group was less likely to have gastrointestinal involvement (P = 0.008) and pulmonary arterial hypertension (PAH), as determined by echocardiography) (P = 0.015) and more likely to have favourable initial forced vital capacity (P = 0.0004), favourable initial lung diffusion capacity for carbon monoxide (P = 0.0002) and a low CT grade (P < 0.001). The final watchful waiting decision model included lack of PAH and limited ILD extent on CT. Application of the model to the cohort revealed that patients who were eligible for watchful waiting (as determined by the model) and underwent this management strategy had better survival than eligible patients who underwent immunosuppressive treatment (P = 0.048, by log-rank test)., Conclusion: Watchful waiting may be effective for SSc-ILD patients who have minimal pulmonary involvement on CT and lack PAH on echocardiography at baseline., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: CD70-expressing CD4 T cells are enriched in RA and promote autoimmunity via co-stimulatory CD70-CD27 interaction. This study aimed to explore the phenotype and cytokine production of CD70(+) CD4 T cells in RA., Methods: Peripheral blood mononuclear cells from 32 RA patients were isolated and frequencies of CD70(+) cells within different CD4 T subsets were analysed using flow cytometry. IFN-γ and IL-17 production were compared between the CD70(+) and CD70(-) cells. Expression of master transcription factors T-bet, GATA3 and retinoic acid-related orphan receptor gamma t (RORγt) were examined by real-time PCR. Results are presented as mean (s.e.m.)., Results: CD4 T cells of healthy controls rarely expressed CD70 as compared with CD4 T cells of RA patients [mean 0.9% (s.e.m. 0.3%) vs 7.6 (0.6), P < 0.001]. In RA, CD70(+) cells were present within all CD4 T cell subsets, i.e. CD45RA(+)CCR7(+) naive, CD45RA(-)CCR7(+) central memory, CD45RA(-)CCR7(-) effector memory and CD45RA(+)CCR7(-) terminally differentiated effector memory T cells with a mean frequency of 3.9% (s.e.m. 1.1%), 4.0 (0.5), 4.2 (0.7) and 9.4 (4.3), respectively. As compared to CD70(-) CD4 T cells, CD70(+) CD4 T cells produced significantly more IFN-γ and IL-17 after short activation. CD70(+) CD4 T cells preferentially expressed transcription factor RORγt., Conclusion: CD70(+) CD4 T cells are enriched in RA and may directly contribute to RA pathogenesis by producing IFN-γ and IL-17. Targeting CD70(+) CD4 T cells might offer new therapeutic opportunities in RA., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: RP is a reversible vasoconstriction of digital arteries that causes pain and skin discoloration. This study compared the efficacy of the new phosphodiesterase type 5 inhibitor udenafil with that of the calcium channel blocker amlodipine in the treatment of secondary RP., Methods: A total of 29 patients with secondary RP associated with connective tissue diseases were enrolled in this double-blind, randomized, cross-over study. The patients were randomized to receive udenafil 100 mg/day or amlodipine 10 mg/day for 4 weeks. After a washout period they were crossed over to the other drug for another 4 weeks. The primary outcome was RP frequency before and after treatment. The secondary outcomes were RP condition scores, RP duration, number of digital ulcers, HAQ, physician global assessment and digital artery flow before and after treatment., Results: Amlodipine and udenafil both decreased the rate of RP attack significantly. The drugs did not differ in terms of RP frequency or any of the secondary outcomes except for digital blood flow; udenafil improved it significantly better than amlodipine (P = 0.021). Udenafil was well tolerated without serious adverse effects., Conclusion: Udenafil and amlodipine have comparable efficacy in improving RP attacks. In addition, udenafil improves the blood flow in digital arteries compared with amlodipine., Trial Registration: www.clinicaltrials.gov, protocol number NCT01280266.

Objective: To investigate the significant determinants of health-related quality of life (HRQOL) and the association of the EULAR Sjögren's syndrome patient reported index (ESSPRI) with clinical parameters including HRQOL in Korean patients with primary Sjögren's syndrome (pSS) compared with non-SS sicca patients., Methods: We prospectively analysed 104 pSS and 42 non-SS sicca patients. Clinical data including Short Form 36 (SF-36) scores, self-assessments for symptoms and ESSPRI were cross-sectionally collected., Results: Although most self-assessments and HRQOL statuses were comparable, different association patterns between HRQOL and symptoms were observed in pSS and non-SS sicca patients. pSS patients with low HRQOL had significantly higher ESSPRI scores [P = 7.6 × 10(-6) for physical component summary (PCS) subgroups and P = 0.0015 for mental component summary (MCS) subgroups] and ESSPRI scores showed a significant association with all SF-36 scales in pSS patients (all P ≤ 0.0020). Moreover, in multivariate linear regression analyses, ESSPRI (P = 0.035) and depression (P = 4.1 × 10(-14)) were significantly correlated with the PCS and the MCS, respectively. However, in the non-SS sicca group, xerostomia inventory (XI) scores were higher in the low PCS subgroup (P = 0.031) and this correlated with five SF-36 scales (all P ≤ 0.046). XI scores (P = 0.0039) and anxiety (P = 7.9 × 10(-10)) were the main determinants of the PCS and MCS, respectively., Conclusion: HRQOL levels were differentially associated with clinical facets in pSS and non-SS sicca patients, although the groups had similar clinical symptoms and HRQOL reduction. Because depression and ESSPRI are major determinants of HRQOL in Korean pSS patients, ESSPRI is suggested to be disease-specific for pSS.

Objective: Behçet's disease is one of the major aetiologies of uveitis causing blindness in Asian countries. A genome-wide association study identified six microsatellite markers as disease susceptibility loci for Japanese patients with Behçet's disease. To confirm our recent results, these microsatellite markers were examined in a Korean population as a replication study., Methods: Study participants included 119 Behçet's disease patients and 141 controls. All were enrolled in Korea. Association between the six reported microsatellite markers (D3S0186i, D6S0014i, D6S0032i, 536G12A, D12S0645i and D22S0104i) and Behçet's disease was analysed. HLA-B was genotyped by sequence-based typing methods., Results: A microsatellite marker located near the HLA-B region demonstrated significant association with Behçet's disease (P = 0.028). The genotype and phenotype frequencies of the HLA-B*51 gene were significantly increased in patients (23.1 and 39.5%, respectively) compared with healthy controls (11.2 and 20.1%, respectively; P < 0.001)., Conclusion: Microsatellite analysis revealed that the HLA-B*51 gene was strongly associated with Behçet's disease in a Korean population.

Objective: NSAIDs are commonly prescribed to control gout attacks in patients with hyperuricaemia. We investigated risk factors for NSAID-induced acute kidney injury (AKI) in patients with hyperuricaemia., Methods: We identified 328 patients with hyperuricaemia treated with NSAIDs at Seoul National University Hospital between December 1998 and January 2008 to investigate risk factors for NSAID-induced AKI. The risk factors evaluated included age, sex, BMI, comorbidity, NSAID COX-2 selectivity, baseline glomerular filtration rate (GFR), serum uric acid, serum albumin, haemoglobin level, ratio of blood urea nitrogen and serum creatinine and the use of allopurinol. After extracting possible risk factors through univariate analysis, multivariate logistic regression analysis was performed with backward selection to derive a risk model for NSAID-induced AKI in patients with hyperuricaemia., Results: Thirty (9.1%) NSAID users developed AKI. Univariate analysis revealed that old age (P = 0.008), low GFR (P = 0.001), low serum albumin (P < 0.001) and low haemoglobin levels (P < 0.001) were possible risk factors. Multivariate logistic regression analysis showed that low baseline GFR [odds ratio (OR) 4.86, 95% CI 1.27, 18.55, P = 0.021, for GFR 15-29 vs ≥60 ml/min/1.73 m(2)] and low serum albumin (OR 4.43, 95% CI 1.82, 10.80, P = 0.001, for albumin ≤4 vs >4 g/dl) are risk factors for NSAID-induced AKI in patients with hyperuricaemia., Conclusion: Low GFR and low serum albumin are risk factors for AKI in hyperuricaemic patients treated with NSAIDs. Our results suggest that NSAIDs should be used with caution in patients with low serum albumin.

Objective: The present study aimed to investigate the salivary chemokine levels in patients with primary SS (pSS) and compare them with those in patients with non-SS sicca symptoms or non-sicca controls., Methods: Unstimulated and stimulated whole saliva samples were obtained from pSS patients (n = 30) and age- and gender-matched patients with non-SS sicca (n = 30) and non-sicca healthy controls (n = 25). Salivary CCL2, CCL3, CCL4, CXCL8 and CXCL10 levels were measured using a Luminex bead-based multiplex assay., Results: Patients with pSS had significantly different distributions of salivary CCL3 (P = 0.0001 by the Kruskal-Wallis test), CCL4 (P < 0.00001), CXLC8 (P < 0.0001) and CXCL10 (P < 0.05) levels in unstimulated saliva and all chemokine levels in stimulated saliva when compared with non-SS sicca and non-sicca controls. In comparison with chemokine production rate, the CXCL8 and CXCL10 production rates were significantly higher in pSS than in non-SS sicca controls (P < 0.01 by the Mann-Whitney test). Logistic regression analyses revealed that salivary CXCL8 (P < 0.05) and CXCL10 (P < 0.05) were the significant discriminating chemokines between the pSS and non-SS sicca groups. Although CXCL8 and CXCL10 levels were not correlated with the focus scores, CXCL8 and CXCL10 levels were significantly associated with salivary gland dysfunction., Conclusion: These results support the notion that CXCL8 or CXCL10 chemokine plays a role in the pathogenesis of pSS.

Objectives: HLA-B51 is strongly associated with Behçet's disease (BD) in any ethnic background. We recently reported that another gene, Toll-like receptor-4 (TLR4) is also implicated in BD in a Japanese population. To confirm these results, we investigated polymorphisms in the TLR4 gene in Korean patients with BD., Methods: In this study, 119 patients with BD and 141 healthy controls were enrolled; every participant was a Korean. Nine single nucleotide polymorphisms previously detected in TLR4 by direct sequencing were analysed for an association with BD., Results: The most frequent haplotype, TAGCGGTAA, was significantly increased in HLA-B*51-positive BD patients (49.5%), compared with healthy control participants [32.3%; P = 0.029; odds ratio (OR) = 2.01; 95% CI 1.25-3.23]. This haplotype was also significantly increased in BD patients with arthritis (48.2%; P = 0.003; OR = 1.96; 95% CI 1.26-3.26). There were no significant differences in the allele and genotype frequencies of patients and controls for each single nucleotide polymorphism., Conclusions: The haplotype of TLR4 may increase the risk for developing BD and the complication of arthritis in the Korean population.

Objectives: Recently, autoantibodies directed against muscarinic type 3 receptor (M3R) have been reported in patients with primary SS. However, the precise epitope(s) of the M3R that interacts with SS autoantibodies remains unclear. The aim of this study was to identify the functional epitope of M3R which interacts with SS immunoglobulin G (IgG)., Methods: Purified IgGs were obtained from the sera of seven SS patients (six primary and one secondary SS) and two normal persons. We examined whether SS IgG inhibits M3R function and identified the epitope using six synthetic peptides covering all the extracellular domains of M3R by microspectrofluorimetry and surface plasmon resonance-based optical biosensor system (BIAcore system)., Results: A volume of 0.5 mg/ml SS IgG inhibited carbachol (CCh)-induced [Ca(2+)](i) transient (CICT) in human submandibular gland (HSG) cells. However, co-incubation of SS IgG with the 6th peptide (514-527 amino acid region) corresponding to the third extracellular loop of M3R, recovered CICT. The result was further confirmed by BIAcore analysis. We found that the 6th peptide interacts with IgGs from three primary SS patients in a concentration-dependent manner. The synthetic peptide which consists of amino acids 228-237 corresponding to the COOH-terminus of the second extracellular loop of M3R also bound to SS IgG. However, normal IgGs did not interact with the 6th peptide., Conclusions: The results suggest that the third extracellular loop of M3R represents a functional epitope bound by SS IgG, and thereby partly inhibits M3R function.

Objective: Knee osteoarthritis (OA) is prevalent among the elderly in Asian countries; however, the utilization of total knee replacement (TKR) is unknown. Using data from a national registry, we sought to estimate the incidence of TKR by age and sex, and the trend for TKR utilization from 2002 to 2005 in South Korea., Methods: Reimbursement records from all hospitals in South Korea were extracted from the Health Insurance Review Agency (HIRA) database. Records with both the procedure code corresponding to a TKR and the diagnosis code of knee OA were selected. We estimated the age- and sex-specific rates of TKR. To compare the rate of TKR between men and women, we calculated age-standardized risk ratios. A TKR registry from a single centre containing more clinical information was analysed, and the differences in the clinical features between men and women were compared., Results: From 2002 to 2005, 47 961 TKRs were performed in subjects over the age of 40 yrs due to OA. The rate of TKR has increased over the 4 yrs and was much higher in women than in men. Compared with men, the age-standardized rate ratios for TKR in women ranged from 7.4 to 8.0. The single-centre registry data revealed that there was no difference in age, disease duration and the Kellgren-Lawrence grade at the time of surgery between men and women., Conclusion: Using a national database, we found that the rate of TKR increased steadily from 2002 to 2005 in South Korea. The TKR rate in women was much higher than that in men. Risk factors that account for such disparity in TKR utilization need to be further investigated.

Objective: To assess the prevalence, characteristics and prognostic factors of interstitial lung disease (ILD) in Korean patients with polymyositis (PM), dermatomyositis (DM) and amyopathic dermatomyositis (ADM)., Methods: We reviewed the medical records of 72 consecutive PM and DM patients, including six patients with ADM, who were seen at the Rheumatology Clinic of Seoul National University Hospital between 1984 and 2003., Results: Twenty-nine PM/DM patients (40.3%) developed ILD. Anti-Jo-1 antibody and arthralgia were associated with the presence of ILD (P = 0.022 and P = 0.041, respectively), whereas dysphagia was more frequently found in patients without ILD (P = 0.041). Lung biopsies revealed diffuse alveolar damage (DAD) (n = 2), usual interstitial pneumonia (UIP) with DAD (n = 2), UIP (n = 1), and non-specific interstitial pneumonia (n = 2). Of the 29 patients, 11 (37.9%) died. The mean survival time in ILD patients was significantly shorter than in those without ILD (13.8+/-1.8 vs 19.2+/-0.9 yr, P = 0.017). Poor survival in ILD patients was associated with a Hamman-Rich-like presentation (P = 0.0000), ADM features (P = 0.0001) and an initial forced vital capacity (FVC) < or =60% (P = 0.024)., Conclusions: ILD was observed in 40.3% of Korean PM/DM patients and was associated with poor survival. A Hamman-Rich-like presentation, ADM features and an initial FVC < or =60% were associated with poor survival in ILD.

Objective: We investigated the clinical features of Korean patients with adult-onset ankylosing spondylitis (AAS) and examined the differences between AAS patients with and without peripheral joint disease (PJD)., Methods: We studied 67 consecutive patients with primary AAS who visited the rheumatology clinic of a tertiary referral hospital. All patients experienced joint symptoms after the age of 15 and fulfilled the modified New York criteria for ankylosing spondylitis. Hips and shoulders were not considered as peripheral joints., Results: The male-to-female ratio was 8.6:1.0. Mean age at disease onset was 22.3 +/- 5.5 (mean +/- s.d.) yr and disease duration was 10.8 +/- 8.0 yr. Spinal symptoms were the first manifestations in 80.6% of patients. During the disease course, hip, shoulder and peripheral joint involvement were found in about 60% of patients. In patients with PJD, the most commonly affected joints were the knees and ankles. The pattern of PJD, in most cases, was asymmetrical and mono/oligoarticular. AAS patients with PJD had fewer spinal symptoms than those without PJD as a presenting feature (71.8 vs 92.9%, P = 0.035). The modified Schober test showed greater increments in patients with PJD (4.9 +/- 2.4 vs 3.0 +/- 2.4 cm, P = 0.002). Forced vital capacity was better in patients with PJD (79.0 +/- 11.4 vs 70.8 +/- 15.5% of predicted value, P = 0.016). Totally ankylosed sacroiliitis, spinal squaring and syndesmophytes on radiographs were less common in the patients with PJD than in those without PJD (33.3 vs 64.2%, P = 0.012; 20.5 vs 67.9%, P = 0.000; and 38.5 vs 71.4%, P = 0.008, respectively)., Conclusion: Peripheral joints as well as shoulder and hip joints were more frequently involved during the disease course in Korean AAS patients compared with earlier reports in Caucasians. The general joint involvement pattern of PJD was similar to patterns reported previously. Our data suggest that, clinically and radiographically, AAS patients with PJD have a less severe spinal disease course than those without PJD.

Objective: PG201 has been formulated using 12 herbs known to have anti-inflammatory and protective effects on damaged tissue and bone among other functions. The present study was done in order to assess the therapeutic effects of PG201 in collagen-induced arthritis (CIA) in mice., Methods: DBA/1 mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with PG201 orally at 10 mg/kg once a day for 18 days. Paws were evaluated macroscopically for redness, swelling and deformities. The levels of TNF-alpha and IL-1beta in the ankle were examined. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. Molecular indicators related to CIA pathology were analysed by measuring the serum levels of matrix metalloproteinase 2 (MMP-2), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) and the anti-inflammatory cytokines interleukin (IL)-4 and IL-10., Results: Administration of PG201 significantly suppressed the progression of CIA and inhibited the production of TNF-alpha and IL-1beta in the paws. The erosion of cartilage was dramatically reduced in mouse knees after treatment with PG201. In the serum of PG201-treated mice, the level of TIMP-2 and the ratio of TIMP-2 to MMP-2 were significantly elevated, and the level of IL-4, but not of IL-10, was increased., Conclusion: Administration of PG201 has therapeutic effects on CIA. Protection of cartilage was particularly prominent. PG201 is a potential therapy for rheumatoid arthritis.

Objectives: To identify genes which are more highly expressed in the peripheral blood mononuclear cells (PBMC) of patients with spondyloarthropathy (SpA), rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in comparison to normal subjects., Methods: A 588-gene microarray was used as a screening tool to select a panel of such genes from PBMC of these subjects and of normal subjects. Results were then validated by reverse transcription-polymerase chain reaction (RT-PCR)., Results: The following genes were more highly expressed in arthritis patients than in normal subjects: macrophage differentiation marker MNDA (myeloid nuclear differentiation antigen), MRP8 and MRP14 (migratory inhibitory factor-related proteins); signalling molecules JAK3 (janus kinase 3) and MAP kinase p38 (mitogen-activated protein kinase); receptors TNFR2/p75, C-C-chemokine receptor type 1 (CCR1), C-X-C-chemokine receptor type 4 (CXCR4) and integrin beta1; and the cytokines/chemokines interleukin (IL) 1beta and IL-8. Expression of CXCR4 was unexpectedly high among all arthritis subjects. Using RT-PCR, ELISA and immunohistology, expression of stromal cell-derived factor 1 (SDF-1) was demonstrated in arthritis joints., Conclusions: The CXCR4/SDF-1 is a potential pro-inflammatory axis for RA, PsA and SpA.