Real-world effectiveness of a single conventional disease-modifying anti-rheumatic drug (cDMARD) plus an anti-TNF agent versus multiple cDMARDs in rheumatoid arthritis: a prospective observational study.

Objective: The objective of this prospective, observational multicenter study (NCT03264703) was to compare the effectiveness of single conventional disease-modifying anti-rheumatic drug (cDMARD) plus anti-tumor necrosis factor (TNF) therapy versus multiple cDMARD treatments in patients with moderate-to-severe rheumatoid arthritis (RA) following cDMARD failure in the real-world setting in South Korea. Methods: At the treating physicians' discretion, patients received single cDMARD plus anti-TNF therapy or multiple cDMARDs. Changes from baseline in disease activity score 28-joint count with erythrocyte sedimentation rate (DAS28-ESR), corticosteroid use, and Korean Health Assessment Questionnaire (KHAQ-20) scores were evaluated at 3, 6, and 12 months. Results: Of 207 enrollees, the final analysis included 45 of 73 cDMARD plus anti-TNF and 91 of 134 multiple-cDMARD recipients. There were no significant between-group differences (BGDs) in ANCOVA-adjusted changes from baseline in DAS28-ESR at 3, 6 (primary endpoint), and 12 months (BGDs -0.18, -0.38, and -0.03, respectively). More cDMARD plus anti-TNF than multiple-cDMARD recipients achieved a >50% reduction from baseline in corticosteroid dosage at 12 months (35.7% vs 14.6%; p=0.007). Changes from baseline in KHAQ-20 scores at 3, 6, and 12 months were significantly better with cDMARD plus anti-TNF therapy than with multiple cDMARDs (BGD -0.18, -0.19, and -0.19 points, respectively; all p≤0.024). Conclusion: In the real-world setting, relative to multiple cDMARDs, single cDMARD plus anti-TNF therapy significantly improved quality-of-life scores and reduced corticosteroid use, with no significant BGD in disease activity, in RA patients in whom previous cDMARD therapy had failed.

Association of HLA-DRB1 locus with treatment response to abatacept or TNF inhibitors in patients with seropositive rheumatoid arthritis.

The strongest genetic risk factor for rheumatoid arthritis (RA) has been known as HLA-DRB1 based on amino acid positions 11, 71, and 74. This study analyzed the association between specific HLA-DRB1 locus and treatment response to abatacept or TNF inhibitors (TNFi) in patients with seropositive RA. A total of 374 Korean RA patients were treated with abatacept (n = 110) or TNFi (n = 264). Associations between HLA-DRB1 and treatment response after 6 months were analyzed using multivariable logistic regression. Seropositive RA patients with HLA-DRB1 shared epitope (SE) had a favorable response to abatacept (OR = 3.67, P = 0.067) and an inversely associated response to TNFi (OR 0.57, P = 0.058) based on EULAR response criteria, but the difference was not statistically significant in comparison to those without SE. In analyses using amino acid positions of HLA-DRB1, a significant association was found between valine at amino acid position 11 of SE and good response to abatacept (OR = 6.46, P = 5.4 × 10-3). The VRA haplotype also showed a good response to abatacept (OR = 4.56, P = 0.013), but not to TNFi. Our results suggest that treatment response to abatacept or TNFi may differ depending on HLA-DRB1 locus in seropositive RA, providing valuable insights for selecting optimal therapy.

Description of the mealtime of older adults with dementia in a long-term care facility: A video analysis.

This study analyzed the mealtime structure of older adults with dementia in long-term care facilities. The study conducted video observations at 2 long-term care facilities with 10 residents and 24 staff members, resulting in 41 dyads. The average mealtime duration was 12.21 ± 5.16 minutes; the average time of a single intake was 0.21 ± 0.21 minutes; and the median of the eating interval was 0.17 minutes. The average verbal assistance time was 1.41 ± 1.31 minutes; the average verbal assistance frequency was short (23.92 ± 15.50 times). During mealtime, residents had an average of 5.00 ± 4.07 instances of failing to eat properly. The video analysis emphasized the necessity of implementing a mealtime assistance program that incorporates patient-centered education for the staff and ensures sufficient staffing to provide high-quality meals for residents in long-term care facilities.

Transcriptomic network analysis reveals key drivers of response to anti-TNF biologics in patients with rheumatoid arthritis.

OBJECTIVE: Anti-TNF biologics have been widely used to ameliorate disease activity in patients with rheumatoid arthritis (RA). However, a large fraction of patients show a poor response to these agents. Moreover, no clinically applicable predictive biomarkers have been established. This study aimed to identify response-associated biomarkers using longitudinal transcriptomic data in two independent RA cohorts. METHODS: RNA sequencing data from peripheral blood cell samples of Korean and Caucasian RA cohorts before and after initial treatment with anti-TNF biologics were analyzed to assess treatment-induced expression changes that differed between highly reliable excellent and null responders. Weighted correlation network, immune cell composition, and key driver analyses were performed to understand response-associated transcriptomic networks and cell types and their correlation with disease activity indices. RESULTS: In total, 305 response-associated genes showed significantly different treatment-induced expression changes between excellent and null responders. Co-expression network construction and subsequent key driver analysis revealed that 41 response-associated genes played a crucial role as key drivers of transcriptomic alteration in four response-associated networks involved in various immune pathways: type I interferon signalling, myeloid leucocyte activation, B cell activation, and NK cell/lymphocyte-mediated cytotoxicity. Transcriptomic response scores that we developed to estimate the individual-level degree of expression changes in the response-associated key driver genes were significantly correlated with the changes in clinical indices in independent patients with moderate or ambiguous response outcomes. CONCLUSIONS: This study provides response-specific treatment-induced transcriptomic signatures by comparing the transcriptomic landscape between patients with excellent and null responses to anti-TNF drugs at both gene and network levels.

Comparative effectiveness of JAK inhibitors and biologic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis.

BACKGROUND/AIMS: We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs. METHODS: A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)-28- erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs). RESULTS: Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups. CONCLUSION: Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.

Pregnancy Outcomes Associated With Biologic Agent Exposure in Patients With Several Rheumatic Diseases and Inflammatory Bowel Diseases.

BACKGROUND: This study aimed to analyze pregnancy outcomes based on biologic agents use in women using the nationwide population-based database. METHODS: The study used the claims database to identify women of childbearing age with several rheumatic (rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis) and inflammatory bowel diseases (Crohn's disease and ulcerative colitis) who had pregnancy-related codes between January 2010 and December 2019. We analyzed live births and adverse pregnancy outcomes based on the previous use of biologics. We also stratified the patients according to duration of biologic agent exposure before pregnancy and the use of biologics during pregnancy to analyze the pregnancy outcomes by subgroups. RESULTS: We identified 4,787 patients with pregnancy events. Among them, 1,034 (21.6%) used biologics before pregnancy. Live birth rate was not different between the biologics group and biologics naïve group (75.0% vs. 75.2%). Multivariate analyses showed that biologics use was associated with higher risk of intrauterine growth retardation (odds ratio [OR], 1.780) and lower risk of gestational diabetes mellitus (OR, 0.776) compared with biologics naïve. Biologics use during pregnancy was associated with higher risk of preterm delivery (OR, 1.859), preeclampsia/eclampsia (OR, 1.762), intrauterine growth retardation (OR, 3.487), and cesarean section (OR, 1.831), but lower risk of fetal loss (OR, 0.274) compared with biologics naïve. CONCLUSIONS: Although there was no difference in live birth rate between the biologics group and biologics naïve group, biologics use seems to be associated with several adverse pregnancy outcomes, especially in patients with biologics during pregnancy. Therefore, patients with biologics during pregnancy need to be carefully observed for adverse pregnancy outcomes.

Body change stress, sexual function, and marital intimacy in korean patients with breast cancer receiving adjuvant chemotherapy: A cross-sectional study.

Objective: A crucial factor influencing the quality of life of patients with breast cancer is marital intimacy, which, along with emotional support, helps them overcome difficult treatments. This study aimed to elucidate and confirm the effects of body change stress and sexual function in marital intimacy. Methods: We conducted a cross-sectional survey on 190 patients with breast cancer. They completed the breast-impact of treatment scale, female sexual function index, and revised dyadic adjustment scale. Results: The patients' average age was 46.27 (6.84), and the age distribution ranged from 25 to 59 years. These variables showed statistically significant differences according to the chemotherapy period (P â€‹< â€‹0.05) and type of surgery (P â€‹< â€‹0.05). Body change stress negatively correlated with sexual function (r â€‹= â€‹-0.523, P â€‹< â€‹0.001) and marital intimacy (r â€‹= â€‹-0.545, P â€‹< â€‹0.001). Sexual function positively correlated with marital intimacy (r â€‹= â€‹0.363, P â€‹< â€‹0.001). Marital intimacy was affected by the changes in body stress (ߠ​= â€‹-0.473, P â€‹< â€‹0.001). Sexual function did not affect marital intimacy (ߠ​= â€‹0.084, P â€‹= â€‹0.289). Conclusions: Changes in body stress and chemotherapy treatment should be considered in patients with breast cancer for better marital intimacy. Intervention strategies that consider the characteristics discussed could improve marital intimacy for patients with breast cancer.

Higher Genetic Risk Loads Confer More Diverse Manifestations and Higher Risk of Lupus Nephritis in Systemic Lupus Erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a highly heritable complex disorder with heterogeneous clinical manifestations. In this study, we aimed to identify the genetic risk load using clinical and serological manifestations in SLE patients. METHODS: We genotyped a total of 1,655 Korean patients with SLE (n = 1,243 as a discovery set and n = 412 as a replication set) using a customized genome-wide single-nucleotide polymorphism (SNP) array, KoreanChip. A weighted genetic risk score (wGRS) for an individual was calculated from 112 well-validated non-HLA SNPs and HLA haplotypes of SLE-risk loci. We analyzed associations between individual wGRS and clinical SLE subphenotypes and autoantibodies using multivariable linear or logistic regression adjusted by onset age, sex, and disease duration. RESULTS: Childhood-onset SLE (<16 years) conferred the highest genetic risk compared with adult-onset (16-50 years) or late-onset (>50 years) SLE (P = 6.8 × 10-6 ). High wGRS significantly increased associations with SLE manifestations, regardless of onset age, sex, and disease duration. Individual wGRS significantly correlated positively with more clinical American College of Rheumatology criteria (ß = 0.143, P = 1.8 × 10-6 ). Subphenotype analysis revealed significant associations between the highest and lowest wGRS quartile with risk of renal disorder (hazard ratio [HR] 1.74, P = 2.2 × 10-8 ) and anti-Sm antibody production (HR 1.85, P = 2.8 × 10-5 ). Higher wGRS markedly modulated the pathogenesis of proliferative and membranous lupus nephritis class III or IV (HR 1.98, P = 1.6 × 10-5 ) and class V (HR 2.79, P = 1.0 × 10-3 ), but especially lupus nephritis class V in anti-Sm-positive SLE (area under the curve 0.68, P = 1.8 × 10-4 ). CONCLUSION: Patients with SLE and high wGRS tended to have earlier age of SLE onset, higher anti-Sm antibody positivity, and more diverse clinical phenotypes. Genetic profiling may predict high risk for lupus nephritis and a diverse clinical course in SLE patients.

MUC5B promoter variant rs35705950, rare but significant susceptibility locus in rheumatoid arthritis-interstitial lung disease with usual interstitial pneumonia in Asian populations.

BACKGROUND: MUC5B variant rs35705950 is the common and most significant risk variant for rheumatoid arthritis-interstitial lung disease (RA-ILD) in Western populations. However, little is known about its significant association with RA-ILD in Asian populations. We here investigate the association of rs35705950 with Korean patients with RA-ILD. METHODS: In this cross-sectional study, we genotyped rs35705950 in 2444 patients with RA. Among them, 683 patients with RA who have chest CT were divided into RA-ILD and RA-noILD. RA-ILD was classified as usual interstitial pneumonia (UIP) and other than UIP. The associations of rs35705950 with RA-ILD and its subtype were analysed using multivariable regression adjusted for age at RA diagnosis. Meta-analysis of a previously reported Japanese dataset and Korean dataset obtained for this study was conducted. RESULTS: The minor allele (T) frequency of rs35705950 was 0.37%, 1.43% and 2.38% in 2444 patients with RA, 105 patients with RA-ILD and 63 patients with UIP, respectively. Genotypic association of rs35705950 with RA-ILD was insignificant (OR 2.49, 95% CI 0.64 to 9.69, p=0.187), but showed significant association with UIP (OR 4.90, 95% CI 1.23 to 19.59, p=0.024) compared with RA-noILD. In meta-analysis (123 UIP and 878 RA-noILD) combining our data with previously reported Japanese data, this variant was found to be significantly associated with UIP (OR 3.51, 95% CI 1.19 to 10.37, p=0.023). CONCLUSION: MUC5B variant rs35705950 is a rare but significant risk factor for Asian patients with RA-ILD with UIP, suggesting a sharing of the genetic background between Asian and Western populations.

Distinct transcriptome architectures underlying lupus establishment and exacerbation.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving multiple immune cells. To elucidate SLE pathogenesis, it is essential to understand the dysregulated gene expression pattern linked to various clinical statuses with a high cellular resolution. Here, we conducted a large-scale transcriptome study with 6,386 RNA sequencing data covering 27 immune cell types from 136 SLE and 89 healthy donors. We profiled two distinct cell-type-specific transcriptomic signatures: disease-state and disease-activity signatures, reflecting disease establishment and exacerbation, respectively. We then identified candidate biological processes unique to each signature. This study suggested the clinical value of disease-activity signatures, which were associated with organ involvement and therapeutic responses. However, disease-activity signatures were less enriched around SLE risk variants than disease-state signatures, suggesting that current genetic studies may not well capture clinically vital biology. Together, we identified comprehensive gene signatures of SLE, which will provide essential foundations for future genomic and genetic studies.

Development of mealtime difficulty scale for older adults with dementia in long-term care facilities.

BACKGROUND: In older patients with dementia, functional dependence on individuals affects their eating behavior, leading to difficulties with meals. In addition to individual factors, several social, cultural, and environmental factors influence mealtime difficulties in older individuals with dementia. Therefore, a measure is required to evaluate the difficulty of eating, considering the different interacting phenomena. METHODS: Mealtime Difficulties Scale for older adults with Dementia (MDSD) was developed through a literature review. A pilot test was undertaken to confirm the meaning of the items and the relevance of mealtime difficulties for older patients with dementia. A panel of six experts examined the content validity of the MDSD. Convenience sampling was used to recruit direct care workers from long-term care facilities, of which 150 were recruited for exploratory factor analysis (EFA) and 208 for confirmatory factor analysis (CFA). RESULTS: The final version of the MDSD included 19 items, with a Cronbach's α of 0.91. The EFA identified three factors ("functional," "caregiving," and "behavioral") that account for 54.6% of the total variance. The CFA confirmed the validity of the instrument. CONCLUSIONS: Evidence to substantiate the validity and reliability of MDSD was found. While this tool has limitations in that it does not ensure convergent validity, it can be considered significant as it can assess the mealtime difficulty among older patients with dementia from different perspectives.

Effect of resistance exercise on serum leptin levels in a prospective longitudinal study of women patients with rheumatoid arthritis.

BACKGROUND: Exercise has an anti-inflammatory effect and reduces fat mass. Leptin has been known to be proinflammatory adipokines mainly produced by adipocytes. However, few studies have investigated the association between exercise and changes in serum leptin levels of patients with RA. This study evaluated the effect of an individualized resistance exercise on inflammatory markers including leptin as well as muscle strength and exercise capacity in patients with rheumatoid arthritis (RA). METHODS: A total of 42 age- and sex-matched participants were assigned to a resistance exercise program (60 min, once a week for 12 weeks, and self-exercise twice a week) or to a control group. Muscle strength, exercise capacities, and inflammatory markers such as cytokines and adipokines were assessed at baseline and at 12 weeks follow-up. Longitudinal changes in muscle strength, exercise capacity, cytokines, and adipokines between groups were tested with repeated measures analysis of variance or using the generalized estimating equation, with adjustment for baseline disease activity score 28-C response protein as a covariate. RESULTS: A total of 37 of 42 female patients with RA completed this prospective intervention study. Grip strength improved significantly in the exercise group (P < 0.05), while no between-group changes were found. Quadriceps contraction power (P for group-time interaction = 0.035 for the right side and P for group-time interaction = 0.012 for the left side) and 6-minute walking distance (P for group-time interaction = 0.021) were all improved significantly in the exercise group compared with the control group. In addition, serum leptin levels were significantly decreased in the exercise group compared with the control group (P for group-time interaction = 5.22 × 10-5), but not the other cytokines or adipokines. The change in serum leptin levels correlated with the changes in fat mass (Rho = 0.491, P= 0.015) and visceral fat area (Rho = 0.501, P= 0.013). CONCLUSION: In addition to muscle strength and exercise capacity, the 12 weeks of individualized resistance exercise reduced serum leptin levels in keeping with body fat mass or visceral fat area, suggesting that serum leptin levels might be a surrogate marker of exercise in RA.

Study on the Improvement of Health and Nutrition Status After a 12-week Protein-Rich Supplementation Regimen in Children and Adolescents With Brain Lesions Disorder.

Through a survey on dietary intake of children and adolescents with brain lesions, the present study aimed to analyze the current status of nutrient intake and examine the effect of high-protein nutrient drink on their nutritional and muscle statuses. The study participants were 90 juvenile participants aged 8-19 years, with brain lesions. The participants were provided with a protein nutrient drink for 12 weeks and a questionnaire survey on dietary intake was performed to analyze the level of nutrient intake before and after ingestion. The physical measurements were taken to determine the improvements in nutrient and muscle statuses. The results showed that, before the intake of protein nutrient drink as a supplement, the participants exhibited lower height, weight, and body mass index than those of the standard levels of healthy individuals, and the level of nutrient intake through diet was lower than those of the required and recommended levels of nutrient intake for Koreans. Conversely, after the intake of protein nutrient drink for 12 weeks, the level of nutrient intake and physical statuses such as weight showed significant improvements. In addition, the muscle status had undergone approximately 10% of change during the intervention with no significant difference. Thus, to ensure an adequate level of nutrient supply to children and adolescents with brain lesions, there is an urgent need to develop a guideline of nutrient intake. The findings in this study are expected to serve as the basic data for such guidelines.

Predictive Factors for Renal Response in Lupus Nephritis: A Single-center Prospective Cohort Study.

Objective: To identify the predictive factors for renal response in patients with lupus nephritis (LN). Methods: Patients and data were extracted from a prospective systemic lupus erythematosus cohort in Korea, in which clinical data were collected at 0, 3, 6, and 12 months after induction therapy. Treatment response of LN were evaluated as a complete response (CR), partial response (PR), or non-response (NR) at 3, 6, and 12 months, respectively. Predictive factors for CR at 6 months were evaluated using multivariable Poisson regression analysis. Results: A total of 75 patients with LN who underwent biopsy was enrolled. The mean age at diagnosis of LN was 28.9±9.7 years, and 68 (90.7%) were female. The frequencies of classes III, IV, III+V, IV+V, and V were 20.0%, 44.0%, 16.0%, 12.0%, and 8.0%, respectively. Compared to relapsed LN, new-onset LN showed a lower percentage of glomerulosclerosis (45.5% vs. 76.2%, p=0.013). The overall proportions of CR, PR, and NR at 6 and 12 months were 52.0%, 26.7%, 21.3% and 50.7%, 24.0%, 25.3%, respectively. In multivariate analysis, age at enrollment (odds ratio [OR]=1.02, p=0.022), relapsed LN (OR=0.71, p=0.037), anti-Ro antibody (OR=0.67, p=0.014), and class III LN (OR=1.48, p=0.001) were associated with CR at 6 months. Conclusion: In our prospective cohort, class III LN was a good predictive factor for CR at 6 months in patients with LN, whereas younger age, relapsed LN, and anti-Ro antibody were poor predictive factors.

Eating Difficulties among Older Adults with Dementia in Long-Term Care Facilities: A Scoping Review.

This paper reports a scoping review of the literature on eating difficulties among older adults with dementia in long-term care facilities to identify key concepts, methods of measuring outcomes, interventions, and related factors. A scoping review was performed using the bibliographic databases PubMed, CINAHL, PsycINFO, and Cochrane Library. A combination of keywords and subject headings related to eating or feeding difficulties was used. Inclusion criteria were limited to materials published in English. A total of 1070 references were retrieved, of which 39 articles were selected after applying the inclusion and exclusion criteria. Articles that met the criteria were published between 1987 and 2020. "Eating disabilities" have been defined as problems related to choosing food and/or the ability to get food to one's mouth, chew, and swallow. Interventions for eating difficulties described in the literature include spaced retrieval training, Montessori training, and feeding skill training. Intrapersonal, interpersonal, and environmental factors related to eating difficulties were identified. This scoping review will provide direct care workers, nursing educators, and administrators with an overview of eating performance and a broad understanding of eating difficulties for older adults with dementia in long-term care facilities.

Factors associated with eating performance in older adults with dementia in long-term care facilities: a cross-sectional study.

BACKGROUND: The purpose of this study was to investigate factors influencing eating performance in older adults with dementia (OAWDs) in long-term care (LTC) facilities. METHODS: This cross-sectional study examined risk factors for compromised eating performance by comparing both independent and dependent older adults with dementia. The study participants were 117 OAWDs in LTC facilities in South Korea. Measurements included (a) general characteristics, (b) activities of daily living (ADL) including eating performance, (c) cognitive function, (d) physical capability, (e) grip strength, (f) Behavioral Psychological Symptoms of Dementia (BPSD), and (g) depression. Data were analyzed by the percentage, mean and standard deviation, Chi-square test, t-test, and logistic regression. RESULTS: The eating independent group had more comorbidities than the dependent group (t = 2.793, p < .006); had significantly higher cognition (t = 4.108, p < .001) and physical capability (t = 5.258, p < .001); and had stronger grip strength (t = 2.887, p = .005). Comorbidities and physical capability were determinants for independent eating performance (Odds Ratio [OR] = 1.969, p = .014; OR = 1.324, p < .001). CONCLUSIONS: It is suggested that maintaining physical capability should be encouraged to support independent eating performance by OAWDs in LTC facilities. The results of this study could serve as a basis for developing function-focused care to maintain the residual eating performance of OAWDs in Korean LTC facilities. This is a subject area that has not been fully explored.

Genetic variants shape rheumatoid arthritis-specific transcriptomic features in CD4+ T cells through differential DNA methylation, explaining a substantial proportion of heritability.

OBJECTIVE: CD4+ T cells have been suggested as the most disease-relevant cell type in rheumatoid arthritis (RA) in which RA-risk non-coding variants exhibit allele-specific effects on regulation of RA-driving genes. This study aimed to understand RA-specific signatures in CD4+ T cells using multi-omics data, interpreting inter-omics relationships in shaping the RA transcriptomic landscape. METHODS: We profiled genome-wide variants, gene expression and DNA methylation in CD4+ T cells from 82 patients with RA and 40 healthy controls using high-throughput technologies. We investigated differentially expressed genes (DEGs) and differential methylated regions (DMRs) in RA and localised quantitative trait loci (QTLs) for expression and methylation. We then integrated these based on individual-level correlations to inspect DEG-regulating sources and investigated the potential regulatory roles of RA-risk variants by a partitioned-heritability enrichment analysis with RA genome-wide association summary statistics. RESULTS: A large number of RA-specific DEGs were identified (n=2575), highlighting T cell differentiation and activation pathways. RA-specific DMRs, preferentially located in T cell regulatory regions, were correlated with the expression levels of 548 DEGs mostly in the same topologically associating domains. In addition, expressional variances in 771 and 83 DEGs were partially explained by expression QTLs for DEGs and methylation QTLs (meQTLs) for DEG-correlated DMRs, respectively. A large number of RA variants were moderately to strongly correlated with meQTLs. DEG-correlated DMRs, enriched with meQTLs, had strongly enriched heritability of RA. CONCLUSION: Our findings revealed that the methylomic changes, driven by RA heritability-explaining variants, shape the differential expression of a substantial fraction of DEGs in CD4+ T cells in patients with RA, reinforcing the importance of a multidimensional approach in disease-relevant tissues.

Clinical and Genetic Risk Factors Associated With the Presence of Lupus Nephritis.

Objective: To elucidate whether clinical features and the weighted genetic risk score (wGRS) were associated with the presence of lupus nephritis (LN). Methods: We retrospectively divided patients with systemic lupus erythematosus (SLE, n=1,078) into biopsy-proven LN (n=507) and non-LN groups (non-LN, n=571) Baseline clinical features, serologic markers, and the wGRS were collected The wGRS was calculated from 112 non-human leukocyte antigen (non-HLA) loci and HLA-DRß1 amino acid haplotypes for SLE Associations among clinical features, wGRS, and the presence of LN were identified. Results: In the multivariate analysis, patients with LN were younger at diagnosis (odds ratio [OR]=0.97, p<0.001), had more pleuritis (OR=2.44, p<0.001) and pericarditis (OR=1.62, p=0.029), had a higher detection rate of anti-double stranded deoxyribonucleic acid (anti-dsDNA antibodies, OR=2.22, p<0.001), anti-Smith antibodies (anti-Sm antibodies, OR=1.70, p=0.002), low level of complement (OR=1.37, p=0.043) and absence of antiphospholipid antibodies (aPL antibodies, OR=1.60, p=0.002), and had higher wGRS (OR=1.16, p=0.012) Mediation analysis suggested that anti-Sm antibodies and low complement could be mediators in the relationship between high wGRS and the presence of LN. Conclusion: Onset age, pleuritis, pericarditis, several serologic markers, and wGRS were associated with the presence of LN Anti-Sm antibodies and low complement appeared to mediate the indirect relationship between wGRS and the presence of LN.

Allele-Specific Quantification of HLA-DRB1 Transcripts Reveals Imbalanced Allelic Expression That Modifies the Amino Acid Effects in HLA-DRß1.

OBJECTIVE: HLA association fine-mapping studies have shown the effects of missense variants in HLA-DRB1 on rheumatoid arthritis (RA) susceptibility, prognosis, and autoantibody production. However, the phenotypic effects of expression changes in HLA-DRB1 remain poorly understood. Therefore, we investigated the allele-specific expression of HLA-DRB1 and its effect on an HLA-DRß1 structure-associated trait in RA. METHODS: We quantified the allele-specific expression of each HLA-DRB1 3-field classic allele in 48 Korean RA patients with anti-citrullinated protein antibodies (ACPAs) and 319 healthy European subjects by using both RNA sequencing and HLA-DRB1 genotype data to calculate the relative expression strength of multiple HLA-DRB1 alleles (n = 14 in Koreans and n = 25 in Europeans) in each population. The known association between ACPA level and alanine at position 74 of HLA-DRß1 in ACPA-positive RA was revisited to understand the phenotypic effect of allele-specific expression of HLA-DRB1 by modeling multivariate logistic regression with the genomic dosage or relative expression dosage of Ala-74 in 2 independent sets of 1,723 Korean RA patients with ACPA. RESULTS: The relative expression strength was highly allele-specific, causing imbalanced allelic expression in HLA-DRB1 heterozygotes. The association between HLA-DRß1 Ala-74 and ACPA level in RA was better explained by relative expression dosage of Ala-74 than by the genomic dosage (change in Akaike's information criterion = -6.98). Moreover, the expression variance of Ala-74 in Ala-74 heterozygotes with no genomic variance of Ala-74 was significantly associated with ACPA level (P = 2.26 × 10-3 ). CONCLUSION: Our findings illustrate the advantage of integrating quantitative and qualitative changes in HLA-DRB1 into a single model for understanding HLA-DRB1 associations.

Feasibility of a Mobile Meal Assistance Program for Direct Care Workers in Long-Term Care Facilities in South Korea.

PURPOSE: The purpose of this study was to assess the feasibility and examine the preliminary effectiveness of a mobile application-based meal assistant training program (APP) for use by direct care workers (CAs) assisting residents with dementia in long-term care facilities in South Korea. METHODS: We adopted a mixed methods research design, which included a pre- and post-intervention study and focus group interviews for the feasibility assessment. Participants included 23 dyads of older adults with dementia and their CAs from a long-term care facility in South Korea. Upon completion of the APP intervention, focused group interviews were conducted with six CAs and five nurses. RESULTS: The results of paired t-tests showed that the effects of the APP intervention on the older adults with dementia and their CAs were not significant; however, the results of the focused group interviews support the potential usefulness of the APP for CAs. CONCLUSION: The APP may be applicable to long-term care workers who need meal assistant skills education.