Serum amyloid A expression in liver promotes synovial macrophage activation and chronic arthritis via NFAT5.

Nuclear factor of activated T-cells 5 (NFAT5), an osmo-sensitive transcription factor, can be activated by isotonic stimuli, such as infection. It remains unclear, however, whether NFAT5 is required for damage-associated molecular pattern-triggered (DAMP-triggered) inflammation and immunity. Here, we found that several DAMPs increased NFAT5 expression in macrophages. In particular, serum amyloid A (SAA), primarily generated by the liver, substantially upregulated NFAT5 expression and activity through TLR2/4-JNK signalling pathway. Moreover, the SAA-TLR2/4-NFAT5 axis promoted migration and chemotaxis of macrophages in an IL-6- and chemokine ligand 2-dependent (CCL2-dependent) manner in vitro. Intraarticular injection of SAA markedly accelerated macrophage infiltration and arthritis progression in mice. By contrast, genetic ablation of NFAT5 or TLR2/4 rescued the pathology induced by SAA, confirming the SAA-TLR2/4-NFAT5 axis in vivo. Myeloid-specific depletion of NFAT5 also attenuated SAA-accelerated arthritis. Of note, inflammatory arthritis in mice strikingly induced SAA overexpression in the liver. Conversely, forced overexpression of the SAA gene in the liver accelerated joint damage, indicating that the liver contributes to bolstering chronic inflammation at remote sites by secreting SAA. Collectively, this study underscores the importance of the SAA-TLR2/4-NFAT5 axis in innate immunity, suggesting that acute phase reactant SAA mediates mutual interactions between liver and joints and ultimately aggravates chronic arthritis by enhancing macrophage activation.

Changes in the cholesterol profile of patients with rheumatoid arthritis treated with biologics or Janus kinase inhibitors.

Objective: To assess the effects of biological and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) on lipid profiles in patients with moderate-to-severe rheumatoid arthritis (RA). Methods: This retrospective single-center observational study included patients with RA taking a tumor necrosis factor-α inhibitor (TNFi), abatacept, tocilizumab, or a Janus kinase inhibitor (JAKi) for at least 6 months. Changes in lipid profile were assessed at 6 months after the start of treatment, and associations between changes in lipid profiles and clinical efficacy, concomitant medications, and comorbidities were evaluated. Results: This study included 114 patients treated with TNFi, 81 with abatacept, 103 with tocilizumab, and 89 with JAKi. The mean percentage change (from baseline to 6 months) in total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and non-HDL-C levels was higher in those taking tocilizumab and JAKi than in those taking TNFi and abatacept. A significant change in non-HDL-C was associated with JAKi (versus TNFi odds ratio [OR], 3.228; 95% confidence interval [CI], 1.536~6.785), tocilizumab (versus TNFi OR, 2.203; 95% CI, 1.035~4.689), and statins (OR, 0.487; 95% CI, 0.231~1.024). However, changes in disease activity in 28 joints were not associated with a significant change in non-HDL-C. Conclusion: Tocilizumab- and JAKi-associated increases in serum non-HDL-C levels were observed regardless of changes in disease activity. Statins are recommended for RA patients showing a significant increase in cholesterol levels after initiating biological and targeted synthetic DMARDs.

Identification of MYH9 as a key regulator for synoviocyte migration and invasion through secretome profiling.

OBJECTIVES: 'Invasive pannus' is a pathological hallmark of rheumatoid arthritis (RA). This study aimed to investigate secretome profile of synovial fibroblasts of patients with RA (RA-FLSs), a major cell type comprising the invasive pannus. METHODS: Secreted proteins from RA-FLSs were first identified using liquid chromatography-tandem mass spectrometry analysis. Ultrasonography was performed for affected joints to define synovitis severity at the time of arthrocentesis. Expression levels of myosin heavy chain 9 (MYH9) in RA-FLSs and synovial tissues were determined by ELISA, western blot analysis and immunostaining. A humanised synovitis model was induced in immuno-deficient mice. RESULTS: We first identified 843 proteins secreted from RA-FLSs; 48.5% of the secretome was associated with pannus-driven pathologies. Parallel reaction monitoring analysis of the secretome facilitated discovery of 16 key proteins related to 'invasive pannus', including MYH9, in the synovial fluids, which represented synovial pathology based on ultrasonography and inflammatory activity in the joints. Particularly, MYH9, a key protein in actin-based cell motility, showed a strong correlation with fibroblastic activity in the transcriptome profile of RA synovia. Moreover, MYH9 expression was elevated in cultured RA-FLSs and RA synovium, and its secretion was induced by interleukin-1ß, tumour necrosis factor α, toll-like receptor ligation and endoplasmic reticulum stimuli. Functional experiments demonstrated that MYH9 promoted migration and invasion of RA-FLSs in vitro and in a humanised synovitis model, which was substantially inhibited by blebbistatin, a specific MYH9 inhibitor. CONCLUSIONS: This study provides a comprehensive resource of the RA-FLS-derived secretome and suggests that MYH9 represents a promising target for retarding abnormal migration and invasion of RA-FLSs.

Factors associated with the composition of the gut microbiome in patients with established rheumatoid arthritis and its value for predicting treatment responses.

BACKGROUND: We aimed to investigate the gut microbiota of patients with established rheumatoid arthritis (RA) who have been managed with disease-modifying anti-rheumatic drugs (DMARDs) for a long time. We focused on factors that might affect composition of the gut microbiota. Furthermore, we investigated whether gut microbiota composition predicts future clinical responses to conventional synthetic DMARDs (csDMARDs) in patients with an insufficient response to initial therapy. METHODS: We recruited 94 patients with RA and 30 healthy participants. Fecal gut microbiome was analyzed by 16S rRNA amplificon sequencing; the resulting raw reads were processed based on QIIME2. Calypso online software was used for data visualization and to compare microbial composition between groups. For RA patients with moderate-to-high disease activity, treatment was changed after stool collection, and responses were observed 6 months later. RESULTS: The composition of the gut microbiota in patients with established RA was different from that of healthy participants. Young RA patients (< 45 years) had reduced richness, evenness, and distinct gut microbial compositions when compared with older RA patients and healthy individuals. Disease activity and rheumatoid factor levels were not associated with microbiome composition. Overall, biological DMARDs and csDMARDs, except sulfasalazine and TNF inhibitors, respectively, were not associated with the gut microbial composition in patients with established RA. However, the combination of Subdoligranulum and Fusicatenibacter genera was associated with a future good response to second-line csDMARDs in patients who showed an insufficient response to first-line csDMARDs. CONCLUSION: Gut microbial composition in patients with established RA is different from that in healthy individuals. Thus, the gut microbiome has the potential to predict responses of some RA patients to csDMARDs.

Kynurenine pathway can be a potential biomarker of fatigue in primary Sjögren's syndrome.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease with low quality of life caused by various constitutional symptoms and glandular dysfunction. Although fatigue is one of the most frequent symptoms in pSS, its aetiology or biomarkers are poorly elucidated. We investigated potential relationship between severity of fatigue and the kynurenine pathway in pSS. METHODS: Clinical data and blood samples of 81 patients were obtained from a prospective cohort for pSS and compared with age- and sex-matched healthy controls (HC). Severity of fatigue was defined according to the fatigue domain scores in the ESSPRI. Potential biomarkers related to the kynurenine pathway were determined using ELISA. RESULTS: Of the total, 44 patients were defined as the "severe fatigue (ESSPRI fatigue ≥ 5)" group, whereas 37 as the "less fatigue (ESSPRI fatigue < 5)". Serum tryptophan levels in the severe fatigue group were significantly lower while those of kynurenine were higher. Serum interferon gamma, IDO1, and quinolinic acid levels were mostly higher in the less fatigue group. Kynurenine/tryptophan ratios were distinctly higher in the severe fatigue group than both HC and the less fatigue group (p < 0.001). This ratio showed a strong degree of positive correlation (r = 0.624, p < 0.001) with severity of fatigue in pSS while the other markers showed fair degrees of correlation. CONCLUSIONS: Serum markers related to the kynurenine pathway, especially the kynurenine/tryptophan ratio, may be associated with severity of fatigue in pSS. These results can provide guidance for further investigations on fatigue in pSS.

Dysbiotic but nonpathogenic shift in the fecal mycobiota of patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is closely associated with the oral and gut microbiomes. Fungal cell wall components initiate inflammatory arthritis in mouse models. However, little is known regarding the role of the fungal community in the pathogenesis of RA. To evaluate the association between RA and the gut microbiome, investigations of bacterial and fungal communities in patients with RA are necessary. Therefore, we investigated the compositions and associations of fecal bacterial and fungal communities in 30 healthy controls and 99 patients with RA. The relative abundances of Bifidobacterium and Blautia decreased, whereas the relative abundance of Streptococcus increased, in patients with RA. The relative abundance of Candida in the fecal fungal community was higher in patients with RA than in healthy controls, while the relative abundance of Aspergillus was higher in healthy controls than in patients with RA. Candida species-specific gene amplification showed that C. albicans was the most abundant species of Candida. Ordination analysis and random forest classification models supported the findings of structural changes in bacterial and fungal communities. Aspergillus was the core fecal fungal genus in healthy controls, although Saccharomyces spp. are typically predominant in Western cohorts. In addition, bacterial-fungal association analyses showed that the hub node had shifted from fungi to bacteria in patients with RA. The finding of fungal dysbiosis in patients with RA suggests that fungi play critical roles in the fecal microbial communities and pathogenesis of RA.

Comparison of remission criteria in patients with rheumatoid arthritis treated with biologic or targeted synthetic disease-modifying anti-rheumatic drugs: results from a nationwide registry.

Background: Biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARD) are widely used for treatment of rheumatoid arthritis (RA), enabling patients to better achieve remission. Objective: The objective of the study was to investigate and compare remission rates in RA patients treated with different b/tsDMARDs during the period 2013-2019. Design: A longitudinal observational analysis was performed on data from a nationwide RA registry. Methods: Remission rates in the KOBIO-RA registry were defined by a disease activity score in 28 joints (DAS28), clinical disease activity index (CDAI), simplified disease activity index (SDAI), and Boolean-based assessment. After initiating treatment with b/tsDMARDs, yearly remission rates in response to b/tsDMARDs, either all or as subgroups (tumor necrosis factor-α inhibitors, tocilizumab, abatacept, and Janus kinase inhibitors), were investigated for 5 years. Sustained remission was defined as remission maintained for two consecutive years. Results: Patients (N = 1805) who completed at least one follow-up visit were analyzed (mean age = 55 years; 83.2% female). At month 12, 56.0% of patients achieved remission based on DAS28-C-reactive protein (CRP), 36.2% on DAS28-erythrocyte sedimentation rate (ESR), 10.4% on CDAI, 12.7% on SDAI, and 12.9% on Boolean criteria. Sustained remission rates were 62%, 40%, 13%, 11%, and 8% for the DAS28-CRP, DAS28-ESR, Boolean, SDAI, and CDAI remission criteria, respectively. Remission rates using the DAS28 definition varied most among the b/tsDMARD subgroups. Conclusion: Assessment of sustained remission using the CDAI, SDAI, or Boolean criteria is more stringent, yet congruous with the DAS28-based criteria in RA patients treated with b/tsDMARDs.

Lipidome profile predictive of disease evolution and activity in rheumatoid arthritis.

Lipid mediators are crucial for the pathogenesis of rheumatoid arthritis (RA); however, global analyses have not been undertaken to systematically define the lipidome underlying the dynamics of disease evolution, activation, and resolution. Here, we performed untargeted lipidomics analysis of synovial fluid and serum from RA patients at different disease activities and clinical phases (preclinical phase to active phase to sustained remission). We found that the lipidome profile in RA joint fluid was severely perturbed and that this correlated with the extent of inflammation and severity of synovitis on ultrasonography. The serum lipidome profile of active RA, albeit less prominent than the synovial lipidome, was also distinguishable from that of RA in the sustained remission phase and from that of noninflammatory osteoarthritis. Of note, the serum lipidome profile at the preclinical phase of RA closely mimicked that of active RA. Specifically, alterations in a set of lysophosphatidylcholine, phosphatidylcholine, ether-linked phosphatidylethanolamine, and sphingomyelin subclasses correlated with RA activity, reflecting treatment responses to anti-rheumatic drugs when monitored serially. Collectively, these results suggest that analysis of lipidome profiles is useful for identifying biomarker candidates that predict the evolution of preclinical to definitive RA and could facilitate the assessment of disease activity and treatment outcomes.

Time-integrated Cumulative Parameters Predictive of Radiographic Progression of Rheumatoid Arthritis: Real-world Data From a Prospective Single-center Cohort.

Objective: With many chronic inflammatory diseases, outcomes are determined by assessing both disease activity at presentation and cumulative activity over time. Here, we investigated whether cumulative activity better reflects the radiographic progression (RP) of rheumatoid arthritis (RA) than measurement of activity at a single time point. Methods: From a prospective cohort of RA patients, most of whom were treated with anti-rheumatic drugs, we selected 117 subjects for whom laboratory, clinical, and radiographic parameters potentially influencing RP were monitored serially for more than 1 year. X-ray images of both hands and both feet were scored using the van der Heijde modified total Sharp score (mTSS). In addition to cross-sectional values at baseline, longitudinal and cumulative values for each parameter were calculated in a time-integrated and averaged manner. Results: Among the values measured at baseline, mTSS, but not the baseline erythrocyte sedimentation rate (ESR) or C-reactive protein level, was associated with RP. By contrast, multivariate analyses identified cumulative values such as the cumulative ESR, cumulative tender joint count, cumulative swollen joint count (SJC), and cumulative Disease Activity Score 28-ESR as major determinants of RP. In particular, the cumulative SJC showed the best predictive performance for RP. Conclusion: This study highlights the importance of cumulative indices for predicting progression of RA. Specifically, dynamic and cumulative values of RA activity-related factors, particularly the cumulative SJC, may be the major determinants of RP in the current practice.

Hypergammaglobulinaemia predicts glandular and extra-glandular damage in primary Sjögren's syndrome: results from the KISS cohort study.

OBJECTIVES: To investigate whether temporal changes in immunoglobulin (Ig) levels and persistent hypergammaglobulinaemia cause glandular and extra-glandular damage in patients with primary Sjögren's syndrome (pSS). METHODS: Cumulative demographics and clinical and serological data from pSS patients in the Korean Initiative pSS cohort were evaluated. Persistent hypergammaglobulinaemia was defined as mean IgG levels of ≥1600 mg/dL over 3 years. Salivary gland damage was assessed by measuring salivary flow impairment, and lacrimal gland damage was assessed by examining ocular structural abnormalities. Solid organ damage included neurological and pleuropulmonary damage, renal impairment and lymphoproliferative disease. Independent predictors of glandular and extra-glandular damage in the third year were identified by logistic regression. RESULTS: Of 256 patients with pSS (median age, 55 years; 98% female), 47% had hypergammaglobulinaemia at baseline. IgG levels fell during the first 2 years in patients with hypergammaglobulinaemia at baseline, but not in those with normal IgG levels. Changes in IgG levels were associated with hydroxychloroquine and glucocorticoids. In the third year of follow-up, salivary flow impairment and solid organ damage were present in 71% and 9% of patients, respectively. After adjusting for age and medication use, persistent hypergammaglobulinaemia was associated with salivary flow impairment and solid organ damage in the third year. Patients in whom IgG fell by more than 80 mg/dL from baseline over 2 years showed less solid organ damage. CONCLUSIONS: Persistent hypergammaglobulinaemia was associated with salivary gland and solid organ damage. Decreased IgG may attenuate progression to solid organ dysfunction.

Switching from TNFα inhibitor to tacrolimus as maintenance therapy in rheumatoid arthritis after achieving low disease activity with TNFα inhibitors and methotrexate: 24-week result from a non-randomized, prospective, active-controlled trial.

BACKGROUND: Tapering or stopping biological disease-modifying anti-rheumatic drugs has been proposed for patients with rheumatoid arthritis (RA) in remission, but it frequently results in high rates of recurrence. This study evaluates the efficacy and safety of tacrolimus (TAC) as maintenance therapy in patients with established RA in remission after receiving combination therapy with tumor necrosis factor inhibitor (TNFi) and methotrexate (MTX). METHODS: This 24-week, prospective, open-label trial included patients who received TNFi and MTX at stable doses for ≥24 weeks and had low disease activity (LDA), measured by Disease Activity Score-28 for ≥12 weeks. Patients selected one of two arms: maintenance (TNFi plus MTX) or switched (TAC plus MTX). The primary outcome was the difference in the proportion of patients maintaining LDA at week 24, which was assessed using a logistic regression model. Adverse events were monitored throughout the study period. RESULTS: In efficacy analysis, 80 and 34 patients were included in the maintenance and switched arms, respectively. At week 24, LDA was maintained in 99% and 91% of patients in the maintenance and switched arms, respectively (odds ratio, 0.14; 95% confidence interval, 0.01-1.59). Drug-related adverse effects tended to be more common in the switched arm than in the maintenance arm (20.9% versus 7.1%, respectively) but were well-tolerated. CONCLUSION: This controlled study tested a novel treatment strategy of switching from TNFi to TAC in RA patients with sustained LDA, and the findings suggested that TNFi can be replaced with TAC in most patients without the patients experiencing flare-ups for at least 24 weeks. TRIAL REGISTRATION: Korea CDC CRIS, KCT0005868 . Registered 4 February 2021-retrospectively registered.

Predictors of joint damage in patients with rheumatoid arthritis: focus on short- and long-term effects of intra-articular glucocorticoid injections.

BACKGROUND/AIMS: To investigate the short- and long-term efficacy of intra-articular glucocorticoid injections (IAGI) in patients with rheumatoid arthritis (RA). METHODS: This was a retrospective study of RA patients who had active arthritis in the hand or wrist joints and who received IAGI (or not) as an adjunct to disease-modifying antirheumatic drugs (DMARDs). Short-term efficacy was assessed based on changes in the disease activity score in 28 joints (DAS28) after 3 months and long-term efficacy was assessed based on changes in the van der Heijde Sharp score (HSS) of hand radiographs over 2 years. Radiographic progression was defined as ΔHSS/year ≥ 2. Logistic regression analysis identified predictors of early achievement of low disease activity (LDA) and radiographic progression. RESULTS: Overall, 126 RA patients received IAGI into the hand or wrist joints and 107 were IAGI-naive. After 3 months, 67% of IAGI-treated patients and 48% of IAGI-naive patients achieved LDA (p = 0.002). Over the next 2 years, 35% of patients treated with IAGI showed radiographic progression compared with 27% of IAGI-naive patients (p = 0.2). IAGI plus biologic DMARDs was associated with achievement of LDA in 3 months. Achieving LDA in 3 months (odds ratio [OR], 0.403; 95% confidence interval [CI], 0.192 to 0.847), wrist arthritis (OR, 2.408; 95% CI, 1.184 to 4.897), and baseline HSS (OR, 1.021; 95% CI, 1.003 to 1.039) were associated with radiographic progression. CONCLUSION: IAGI was associated with early achievement of LDA. LDA was associated with slower radiographic progression. The wrist is more vulnerable to joint damage and requires more aggressive treatment.

KOBIO, the First Web-based Korean Biologics Registry Operated With a Unified Platform Among Distinct Disease Entities.

The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.

Effectiveness and safety of biologic and targeted synthetic disease-modifying anti-rheumatic drugs in elderly patients with rheumatoid arthritis: real-world data from the KOBIO Registry.

OBJECTIVES: We aimed to evaluate the clinical outcomes and safety of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) and to identify predictors of treatment responses to b/tsDMARDs in elderly patients with rheumatoid arthritis (RA). METHODS: Data from the nationwide cohort of elderly (≥ 65 years) patients enrolled in the KOBIO Registry were analysed. Clinical outcomes were assessed, including changes in the Simplified Disease Activity Index, after treatment. Adverse events and reasons for drug discontinuation were assessed. Multivariable logistic regression analyses were performed to determine which baseline variables affected treatment responses and adverse events (AE). RESULTS: Elderly patients treated with b/tsDMARDs (n=355) or conventional synthetic DMARDs (csDMARDs) (n=104) were included. The median age was 70 years and 77% were female. After 1 year, 63% of patients in the b/tsDMARD group and 68% in the csDMARD group achieved remission or low disease activity (LDA). Overall, 27% of patients in the b/tsDMARDs group and 24% in the csDMARDs group experienced AE. A total of 43.4% of patients on b/tsDMARDs discontinued therapy due to lack of effectiveness (27%), AE (34%), or other reasons (35%). The estimated median retention of b/tsDMARDs was 2.5 years. Male sex and non-exposure to tobacco at baseline were independent factors associated with achieving remission or LDA after 1 year. Interstitial lung disease (ILD) was the most prominent comorbidity associated with AE. CONCLUSIONS: Treatment with b/tsDMARDs is effective and well tolerated in elderly patients with RA; nonetheless, ILD is a key comorbidity that should be monitored carefully.

Clinical influences of anticentromere antibody on primary Sjögren's syndrome in a prospective Korean cohort.

BACKGROUND/AIMS: This study was performed to clarify influences of anticentromere antibody (ACA) on clinical phenotypes of primary Sjögren's syndrome (pSS) patients in Korea. METHODS: We assessed 318 patients who met the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for pSS. All patients were selected from the Korean Initiative of primary Sjögren's Syndrome (KISS), a prospective cohort. Among them, 53 patients were positive for ACA, while another 265 patients were not. We compared various clinical data including demographic features, extra-glandular manifestations (EGMs), clinical indices, and laboratory values available from the KISS database between the two groups. RESULTS: Patients in the ACA-positive pSS group were older (p = 0.042), and had higher xerostomia inventory scores (p = 0.040), whereas glandular dysfunction represented with Schirmer I test was more severe in the ACA-negative group. More frequent Raynaud's phenomenon and liver involvement (both p < 0.001) and less articular involvement (p = 0.037) were observed among the EGMs in the ACA-positive group. Less frequency of leukopenia (p = 0.021), rheumatoid factor (p < 0.001), anti-Ro/SSA antibody positivity (p < 0.001), and hypergammaglobulinemia (p = 0.006), as well as higher positivity rates of anti-nuclear antibody and anti-topoisomerase antibody (p < 0.001 and p = 0.006, respectively) were found in the laboratory data in the ACA-positive pSS group. CONCLUSION: Considering distinct phenotypes in hematological and serological features and EGMs, we should monitor the occurrence of these clinical features among pSS patients with ACA in caution.

Development of Monitoring System for Assessing Rheumatoid Arthritis within 5 Minutes Using a Drop of Bio-Fluids.

Rheumatoid arthritis (RA) disease activity fluctuates over time. The disease activity score 28 (DAS28ESR) is a widely used and validated scoring system for assessing RA activity; however, it requires time and expertise. This study aimed to develop a new molecular assay capable of rapidly and objectively assessing RA activity. We used a rapid immuno-assay system (FREND™) to measure soluble CD14 (sCD14) levels, which reflect the DAS28ESR. SCD14 concentrations in urine and serum of RA patients were measured, and RA activity and responses to anti-rheumatic drugs were examined at baseline and after 6 months. FREND™ quantified sCD14 levels in a drop of serum and urine accurately and within 5 min. Serum sCD14 concentrations and its changes correlated well with disease activity and treatment responses, and the results were comparable to C-reactive protein. The new composite indices, including the DAS28CD14 and simplified DASCD14, better detected RA activity than a single sCD14 value and correlated strongly with the DAS28ESR. These indices exhibited excellent diagnostic performance for discriminating a good response 6 months after treatment. We developed a new system for assessing RA activity and therapeutic outcome within 5 min. CD14-based composite indices may have utility for accurate and frequent monitoring of RA status.

Clinical Efficacy and Safety of Injection of Stromal Vascular Fraction Derived from Autologous Adipose Tissues in Systemic Sclerosis Patients with Hand Disability: A Proof-Of-Concept Trial.

BACKGROUND: Stromal vascular fraction (SVF) has recently emerged as a potential therapeutic modality, due to its multipotent cellular components in tissue regeneration. Systemic sclerosis (SSc) is a progressive autoimmune disease that results in hand disability by skin fibrosis and microangiopathies. We performed an open-label study to investigate the efficacy and safety of SVF injection in SSc patients (Clinical Trial number: NCT03060551). METHODS: We gathered 20 SSc patients with hand disability, planning for a 24-week follow-up period. SVF was extracted from autologous adipose tissues, processed by the closed system kit, and injected into each finger of SSc patients. We observed various efficacy and safety profiles at each follow-up visit. RESULTS: Among the 20 initially enrolled patients, eighteen received SVF injection, and were completely followed-up for the whole study period. Patients received 3.61 × 106 mesenchymal stem cells into each finger on average. Skin fibrosis, hand edema, and quality of life were significantly improved, and 31.6% of active ulcers were healed at 24 weeks after injections. Semiquantitative results of nailfold capillary microscopy were ameliorated. There was no single serious adverse event related to the procedure. CONCLUSIONS: Injection of SVF derived from autologous adipose tissues is tolerable, and shows clinical efficacy in SSc patients.

Positive histopathologic assessment in salivary glands shows little impact on clinical features of established primary Sjögren's syndrome in a Korean population.

OBJECTIVES: The presence and severity of focal lymphocytic sialadenitis in minor salivary glands is a pathognomonic feature in primary Sjögren's syndrome (pSS). However, it has not been determined whether performing minor salivary gland biopsy (MSGB) in a setting of serologically and clinically established pSS provides additional clinical value. Therefore, we aimed to investigate the necessity of MSGB in established pSS patients with anti-Ro/SSA antibodies. METHODS: We extracted 185 patients with anti-Ro/SSA antibody-positive pSS from the Korean Initiative of pSS study, a prospective cohort study. We assigned them into two groups, 161 patients with focus scores ≥1 and another 24 with focus scores <1. The two groups were compared in various clinical aspects, including the severity of glandular dysfunction, systemic disease activity, extra- glandular manifestations, and other clinical indices and laboratory values. We also evaluated the relationship between focus scores and clinically important variables in pSS. RESULTS: Between the two groups, there were no significant differences in the severity of secretory dysfunction, the frequency of extra-glandular manifestations, systemic disease activity represented by various clinical indices, and laboratory findings possibly predicting the risk for lymphoma. Rather, theSjögren's syndrome disease damage index was higher in the group with focusscores <1. Among all variables, only serum immunoglobulin G levels were correlated with focus scores. CONCLUSIONS: Given the little influence on clinical phenotypes, routine MSGB could be omitted for serologically and clinically established pSS patients, especially in low-risk areas for lymphoproliferative diseases.

Contribution of Personality Traits, Psychological Factors, and Health-Related Quality of Life to Medication Adherence in Patients with Rheumatoid Arthritis.

PURPOSE: This study sought to investigate the associations between personality traits and medication adherence and to identify predictors of good medication adherence in rheumatoid arthritis (RA) patients. MATERIALS AND METHODS: A total of 207 RA patients using disease-modifying anti-rheumatic drugs were invited for an interview and questionnaire study. Medication adherence was measured using the Compliance Questionnaire for Rheumatology (CQR). Personality traits were analyzed with the five-factor model of the Korean version of the Big Five Inventory 10. Psychological factors were assessed with the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and British Columbia Cognitive Inventory. Health-related Quality of Life (HRQoL) and functional disability were evaluated with the EuroQoL-5 dimension questionnaire and Health Assessment Questionnaire. Multivariate logistic regression analyses were performed to investigate predictors of good medication adherence. RESULTS: Nonadherence to medication was reported by 66.7%. The number of daily prescribed pills was higher in the medication adherence group than in the nonadherence group. Concomitant oral glucocorticoid doses were associated with medication adherence. A high level of conscientiousness and diabetes mellitus comorbidity were associated with better medication adherence [odds ratio (OR), 2.11; 95% confidence interval (CI), 1.01-4.38 and OR, 3.00; 95% CI, 1.12-8.07, respectively]. There were no significant differences in psychological factors or HRQoL between medication adherence and nonadherence groups. CONCLUSION: The personality trait of conscientiousness was associated with medication adherence among the five personality traits evaluated. Patients with diabetes mellitus also showed higher medication adherence than those without this comorbidity.