Yi-Rang Yim

Comparison of clinical and serological differences among juvenile-, adult-, and late-onset systemic lupus erythematosus in Korean patients

Objectives We investigated whether systemic lupus erythematosus (SLE) patients could be distinguished based on the time of disease onset and, if so, whether the groups differed in their clinical and laboratory features in ethnically homogeneous Korean patients. Methods We enrolled 201 SLE patients with available clinical data at the time of onset of SLE from the lupus cohort at Chonnam National University Hospital. Sociodemographic, clinical, and laboratory data, including autoantibodies, and concomitant diseases were found at the time of diagnosis of SLE by reviewing patient charts. We divided SLE patients according to age at SLE diagnosis into three groups: juvenile-onset SLE (JSLE, diagnosed at ≤ 18 years), adult-onset SLE (ASLE, diagnosed at 19–50 years), and late-onset SLE (LSLE, diagnosed at >50 years), and compared baseline demographic, clinical, and relevant laboratory findings. Results Of the 201 patients, 27 (14.4%), 149 (74.1%), and 25 (12.4%) were JSLE, ASLE, and LSLE patients, respectively. Fever, oral ulcers, nephritis, anemia, and thrombocytopenia were more common in JSLE patients than ASLE or LSLE patients (p < 0.05, < 0.05, 0.001, < 0.05, and < 0.05, respectively). However, Sjögren’s syndrome was more frequent in LSLE patients than JSLE or ASLE patients (p < 0.05). Disease activity was significantly higher in JSLE patients than in ASLE or LSLE patients (p < 0.001). Anti-dsDNA and anti-nucleosome antibodies were found more frequently in JSLE patients and less frequently in LSLE patients (p < 0.05 and 0.005, respectively) and decreased complement levels were more common in JSLE patients and less common in LSLE patients (p < 0.001, 0.001, and < 0.05, respectively). Conclusions Our results indicate that SLE patients present with different clinical and serological manifestations according to age at disease onset. JSLE patients have more severe disease activity and more frequent renal involvement and LSLE patients have milder disease activity, more commonly accompanied by Sjögren’s syndrome, at disease onset.

The rate of and risk factors for frequent hospitalization in systemic lupus erythematosus: results from the Korean lupus network registry.

Objectives The survival rate of patients with systemic lupus erythematosus has improved in the last few decades, but the rate of hospitalization and health care costs for these patients remain higher than in the general population. Thus, we evaluated the rate of hospitalization and associated risk factors in an inception cohort of Korean patients with lupus. Methods Of the 507 patients with systemic lupus erythematosus enrolled in the KORean lupus NETwork, we investigated an inception cohort consisting of 196 patients with systemic lupus erythematosus presenting within 6 months of diagnosis based on the American College of Rheumatology classification criteria. We evaluated the causes of hospitalization, demographic characteristics, and laboratory and clinical data at the time of systemic lupus erythematosus diagnosis of hospitalized patients and during a follow-up period. We calculated the hospitalization rate as the number of total hospitalizations divided by the disease duration, and defined “frequent hospitalization” as hospitalization more than once per year. Results Of the 196 patients, 117 (59.6%) were admitted to hospital a total of 257 times during the 8-year follow-up period. Moreover, 22 (11.2%) patients were hospitalized frequently. The most common reasons for hospitalization included disease flares, infection, and pregnancy-related morbidity. In the univariate regression analysis, malar rash, arthritis, pericarditis, renal involvement, fever, systemic lupus erythematosus disease activity index > 12, hemoglobin level < 10 mg/dl, albumin level < 3.5 mg/dl, and anti-Sjögren’s syndrome A positivity were associated with frequent hospitalization. Finally, multivariate analysis showed that arthritis, pericarditis, and anti-Sjögren’s syndrome A antibody positivity at the time of diagnosis were risk factors for frequent hospitalization. Conclusions Our results showed that frequent hospitalization occurred in 11.2% of hospitalized patients and arthritis, pericarditis, and anti-Sjögren’s syndrome A antibody positivity at the time of diagnosis were risk factors for frequent hospitalization.

Associations between body composition measurements of obesity and radiographic osteoarthritis in older adults: Data from the Dong-gu Study

BackgroundWe examined the effects of fat deposition on radiographic osteoarthritis (OA) to determine the role of obesity in the pathogenesis of radiographic OA.MethodsData were taken from the Dong-gu cohort, a cross-sectional study of 2,367 subjects. Baseline characteristics, waist circumference (WC), waist-to-hip ratio (WHR), fat mass, and fat percentage were collected, along with X-rays of the knees and hands. Total knee and hand radiographic OA scores were summed using a semi-quantitative grading system, and then stratified by gender using a multiple linear regression model.ResultsAfter adjusting for confounders, weight was the only factor significantly associated with knee radiographic OA, regardless of gender (all p < 0.01). Regarding the hand, fat percentage had the largest effect on radiographic OA in males (p = 0.008), while WHR was the most significant factor in females (p = 0.001). For the knee, fat mass was the most important factor for radiographic OA in males (p = 0.001), while in females, body mass index was the most important factor (p < 0.001). Among the variables, only fat percentage was significantly related to both hand and knee radiographic OA in both genders (all p < 0.01).ConclusionsRegardless of gender, weight was significantly associated with knee radiographic OA. Otherwise, fat deposition correlated with hand and knee radiographic OA in both genders, while the distribution of fat tissue was significantly associated with hand and knee radiographic OA only in females.

Predictors of Switching Anti-Tumor Necrosis Factor Therapy in Patients with Ankylosing Spondylitis

The aim of this study was to investigate the potential predictors of switching tumor necrosis factor (TNF)-α inhibitors in Korean patients with ankylosing spondylitis (AS). The patients who had been treated with TNF-α inhibitors were divided into two groups depending on whether they had switched TNF-α inhibitors. Demographic, clinical, laboratory, and treatment data at the time of initiation of TNF-α inhibitor treatment were compared between switchers and non-switchers, and within switchers according to the reasons for switching. Of the 269 patients, 70 (23%) had switched TNF-α inhibitors once; of these, 11 switched again. The median follow-up time was 52.7 months. Three- and five-year drug survival rates were 52%/48% for infliximab, 62%/42% for etanercept, and 71%/51% for adalimumab, respectively. Switchers were more likely to be prescribed disease-modifying anti-rheumatic drugs than non-switchers. A history of joint surgery and complete ankylosis of the sacroiliac joint was more frequent in switchers. Multivariate Cox’s proportional hazard analysis showed that the use of adalimumab as the first TNF-α inhibitor was less likely to lead to switching and complete ankylosis of the sacroiliac joints was more likely to lead to switching. The principal reasons for switching were drug inefficacy and adverse events, but the differences in the clinical data of these two groups of switchers were not significant. In AS patients who are candidates for TNF-α inhibitor therapy, switching may improve the therapeutic outcome based on clinical information.

Risk factors for treatment failure in osteoporotic patients with rheumatoid arthritis

Objective. No available anti-osteoporotic medication has been shown to completely prevent declines in bone mineral density (BMD) and the resulting increased risk of fracture. The objective of this study was to investigate the risk factors for treatment failure in osteoporotic patients with rheumatoid arthritis (RA). Methods. A retrospective cohort study of 103 patients with RA and osteoporosis was conducted. Patients were divided into two groups for comparison: those whose osteoporosis treatment was effective and those whose treatment failed. Risk factors for treatment failure were identified by univariate and multivariate logistic regression using variables that differed significantly between the groups. Results. Osteoporosis treatment failed in 66 of 103 patients (64.1%). During 14.01 months of follow-up, non-adherence to bisphosphonate use was the most powerful risk factor for treatment failure. Daily glucocorticoid dosage ≥ 7.5 mg/day before the first BMD measurement, immobilization > 3 months, and Disease Activity Score in 28 joints (DAS28) ≥ 3.2 were also significantly related to treatment failure. Conclusion. Our findings indicate that osteoporosis treatment fails frequently in RA patients and adherence to bisphosphonate use, daily glucocorticoid dosage, immobilization, and DAS28 score should be taken into consideration when treating osteoporotic patients with RA.

The Significance of Ectopic Germinal Centers in the Minor Salivary Gland of Patients with Sjögren's Syndrome

We investigated the clinical and biological significance of germinal centers (GC) present in the minor salivary glands of patients with Sjögren’s syndrome (SS). Minor salivary gland tissue biopsies from 93 patients with SS were used to identify GC-like structures, which were confirmed by CD21-positive follicular dendritic cell networks. Patients were compared based upon sociodemographics, glandular and extraglandular manifestations, and laboratory findings including autoantibody profiles, complement, and immunoglobulin levels; EULAR SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured. GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus scores and CRP levels were significantly higher in GC-positive patients than in GC-negative patients; GC-positive patients also exhibit a higher prevalence of rheumatoid factor and anti-SS-A/Ro antibodies compared to GC-negative patients. No differences in glandular or extra-glandular manifestations were evident between groups. In conclusion, SS patients with GC-like structures in the minor salivary glands exhibited laboratory profiles significantly different from those of their GC-negative counterparts. Long-term follow-up of these patients will be necessary to determine whether these laboratory abnormalities are predictive of clinical outcomes.

Comparison of heart rate variability and classic autonomic testing for detection of cardiac autonomic dysfunction in patients with fibromyalgia.

Cardiac autonomic dysfunction (CAD) is frequently found in patients with fibromyalgia (FM). Thus, we evaluated whether heart rate variability (HRV) is superior to the Ewing tests in detecting CAD in FM patients.

The relationships between bone mineral density and radiographic features of hand or knee osteoarthritis in older adults: data from the Dong-gu Study

OBJECTIVE The relationship between OA and osteoporosis has exhibited contradictory features over the past four decades. The aim of this study was to determine using separate analysis of the radiographic features of OA whether various radiographic features of OA were associated differently with BMD in the Korean elderly. METHODS Data were derived from the Dong-gu cohort; 2354 subjects were enrolled in the present cross-sectional study. Baseline characteristics, the BMDs of the lumbar spine and femoral neck measured by DXA, and X-rays of knees and hands were collected. A semi-quantitative grading system was used to estimate the severities of individual radiographic features. We adjusted for confounders using multiple linear regression modelling to analyse the relationships. RESULTS After adjustment for confounders, hand and knee OA total scores were negatively associated with the BMDs of the lumbar spine and femoral neck, except for the total knee OA score and lumbar spine BMD. In detail, hand osteophytes and sclerosis exhibited positive relationships with the BMDs of the lumbar spine and femoral neck, except for hand osteophytes and femoral neck BMD. On the contrary, however, knee joint space narrowing (JSN), hand JSN, and hand subchondral cysts were negatively associated with the BMD of the lumbar spine and femoral neck. Knee JSN and hand subchondral cysts exerted the greatest effects on BMD. CONCLUSION Separate analysis of the radiographic features of OA better reveals associations of OA with the BMD of the lumbar spine and femoral neck.

THU0045 Dysregulated Osteoclastogenesis is Related to Natural Killer T Cell Dysfunction in Rheumatoid Arthritis

Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of multiple synovial joints, and leads to bone and cartilage destruction. Natural killer T (NKT) cells act as a link between innate and adaptive immunity because they are able to activate a variety of immune cells. A previous study conducted using murine models showed that NKT cells have the unique property of enhancing osteoclast progenitor and precursor development. However, the role play by NKT cells in inflammatory bone destruction, such as that associated with RA, remains unknown. Objectives The aims of the present study were to investigate the role of NKT cells during osteoclastogenesis, the mechanism underlying the dysregulation of osteoclastogenesis in RA, and the in vivo effect of α-galactosylceramide (αGalCer)-stimulated NKT cells in a mouse model of collagen-induced arthritis (CIA). Methods Patients with RA (n=25) and healthy controls (n=12) were enrolled in this study. In vitro osteoclastogenesis experiments were performed using peripheral blood mononuclear cells (PBMCs) in the presence of M-CSF and receptor activator of nuclear factor kB ligand (RANKL). PBMCs were cultured in vitro with α-galactosylceramide (αGalCer), and proliferation indices of NKT cells were estimated by flow cytometry. In vivo effects of αGalCer-stimulated NKT cells on inflammation and bone destruction were determined in collagen-induced arthritis (CIA) mice. Results In vitro osteoclastogenesis was found to be significantly inhibited by αGalCer in healthy controls, but not in RA patients. Proliferative responses of NKT cells and STAT-1 phosphorylation in monocytes in response to αGalCer were impaired in RA patients. Notably, αGalCer-stimulated NKT cells inhibited osteoclastogenesis mainly via interferon-γ production, in a cytokine-dependent manner (not by cell-cell contact), and down-regulated osteoclast-associated genes. aGalCer-treated mice showed less severe arthritis and reduced bone destruction. Moreover, proinflammatory cytokine expression in arthritic joints was found to be reduced by aGalCer treatment. Conclusions This study primarily demonstrates that aGalCer-stimulated NKT cells have a regulatory effect on osteoclastogenesis and a protective effect on inflammatory bone destruction. However, it also shows that these effects of aGalCer are diminished in RA patients, and that this is related to NKT cell dysfunction. These findings provide important information for those searching for novel therapeutic strategies to prevent bone destruction in RA. References Hu M, Bassett JH, Danks L, Howell PG, Xu K, Spanoudakis E, et al. Activated invariant NKT cells regulate osteoclast development and function. J Immunol 2011;186:2910-7. Tudhope SJ, von Delwig A, Falconer J, Pratt A, Woolridge T, Wilson G, et al. Profound invariant natural killer T-cell deficiency in inflammatory arthritis. Ann Rheum Dis 2010;69:1873-9. Acknowledgements This study was supported by a grant from the National Research Foundation of Korea funded by the Korean Government (#2013R1A2A2A01067956). Disclosure of Interest None declared

AB0758 The Relationships between Bone Mineral Density and Radiographic Features of Hand or Knee Osteoarthritis in Older Adults: Data from The Dong-Gu Study

Objectives The relationship between osteoarthritis (OA) and osteoporosis has exhibited contradictory features over the past four decades. The aim of this study was to evaluate this relationship using separate analysis of the radiographic features of OA whether various radiographic features of OA were associated differently with bone mineral density (BMD) in the Korean elderly. Methods Data were derived from the Dong-gu cohort; 2,354 subjects were enrolled in the present cross-sectional study. Baseline characteristics, the BMDs of the lumbar spine and femoral neck which was measured by DXA, and X-rays of knees and hands, were collected. A semi-quantitative grading system was used to estimate the severities of individual radiographic features. We adjusted for confounders using multiple linear regression modeling to analyze the relationships. Results After adjustment for confounders, hand and knee OA total scores were negatively associated with the BMDs of the lumbar spine and femoral neck, except for the total knee OA score and lumbar spine BMD. In detail, hand osteophytes and sclerosis exhibited positive relationships with the BMDs of the lumbar spine and femoral neck, except for hand osteophytes and femoral neck BMD. On the contrary, however, knee joint space narrowing (JSN), hand JSN, and hand subchondral cysts were negatively associated with the BMD of the lumbar spine and femoral neck. Knee JSN and hand subchondral cysts exerted the greatest effects on BMD. Conclusions Separate analysis of the radiographic features of OA better reveals associations of OA with the BMD of the lumbar spine and femoral neck. Disclosure of Interest None declared