Factors associated with radiographic progression in patients with Takayasu's arteritis.

OBJECTIVES: To identify the factors related to radiographic progression in patients with Takayasu's arteritis (TAK). METHODS: A retrospective cohort study was conducted among patients with TAK who underwent computed tomography angiography (CTA) at least twice in a 2-5-year interval. Radiographic progression was defined as newly developed and/or aggravated (more than 20%) characteristic CTA findings. Correlation analysis was performed using a multivariate Cox regression model. RESULTS: The cohort included 153 TAK patients with a mean CTA interval of 3.53 years, and 24 (15.7%) showed radiographic progression. Those with progression showed higher acute-phase reactant levels (erythrocyte sedimentation rate [ESR], 26.06 vs. 35.72 mm/h, p=0.040; C-reactive protein [CRP], 0.45 vs. 1.13 mg/dL, p<0.001), were younger at the initial CTA (43.70 vs. 31.81 years, p<0.001), and were more likely to be receiving immunosuppressants (14 [10.9%] vs. 7 [29.2%] patients, p=0.038). Multivariate Cox regression analysis revealed age at the initial CTA (hazard ratio [HR]=0.945, confidence interval [CI]=0.898-0.995, p=0.030) and area under the curve (AUC) of CRP levels (HR=2.126, CI=1.046-4.319, p=0.037) as significant factors for radiographic progression. In a subgroup of patients with high CRP levels, 30.4% (14/24) showed progression; only age at the initial CTA was significantly different (37.03 vs. 27.10 years, p=0.012) between those with and without progression. CONCLUSIONS: Higher CRP levels and younger age were risk factors of radiographic progression in patients with TAK. In the high CRP group, younger patients are more prone to progression and may need aggressive anti-inflammatory treatment.

Inhibitory Effects of AF-343, a Mixture of Cassia tora L., Ulmus pumila L., and Taraxacum officinale, on Compound 48/80-Mediated Allergic Responses in RBL-2H3 Cells.

The purpose of this study was to determine the antiallergic effects of AF-343, a mixture of natural plant extracts from Cassia tora L., Ulmus pumila L., and Taraxacum officinale, on rat basophilic leukemia (RBL-2H3) cells. The inhibitory effects on cell degranulation, proinflammatory cytokine secretion, and reactive oxygen species (ROS) production were studied in compound 48/80-treated RBL-2H3 cells. The bioactive compounds in AF-343 were also identified by HPLC-UV. AF-343 was found to effectively suppress compound 48/80-induced b-hexosaminidase release, and interleukin (IL)-4 and tumor necrosis factor-a (TNF-a) production in RBL-2H3 cells. In addition, AF-343 exhibited DPPH free radical scavenging effects in vitro (half-maximal inhibitory concentration (IC50) = 105 µg/mL) and potently inhibited compound 48/80-induced cellular ROS generation in a 2',7'-dichlorofluorescein diacetate (DCFH-DA) assay. Specifically, treatment with AF-343 exerted stronger antioxidant effects in vitro and antiallergic effects in cells than treatment with three single natural plant extracts. Furthermore, AF-343 was observed to contain bioactive compounds, including catechin, aurantio-obtusin, and chicoric acid, which have been reported to elicit antiallergic responses. This study reveals that AF-343 attenuates allergic responses via suppression of b-hexosaminidase release, IL-4 and TNF-a secretion, and ROS generation, perhaps through mechanisms related to catechin, aurantio-obtusin, and chicoric acid. The results indicate that AF-343 can be considered a treatment for various allergic diseases.

Increased Overall Heart Rate Irregularity Risk by Hyperuricemia in the General Population: Results from the Korean National Health and Nutrition Examination Survey.

Background and objectives: Hyperuricemia is one of the well-known cardiovascular risk factors. There is a growing interest in the association between hyperuricemia and arrhythmia. We used the representative sample data of Korean population to study the association between hyperuricemia and heart rate irregularity (HRI) that reflects total arrhythmia. Materials and Methods: We performed weighted multivariate logistic regression analysis to assess the association between hyperuricemia and HRI. Results: Of the 10,827 subjects, 1308 (13.2%) had hyperuricemia and 130 (1%) had HRI. In the presence of hyperuricemia, HRI was three times higher than that in the absence of hyperuricemia (OR 2.98, 95% CI 1.71-5.18). The risk of HRI was highest in subjects with both hypertension and hyperuricemia. In the subgroup analysis, the association of hyperuricemia with HRI was most pronounced in the smoker group. Conclusions: Hyperuricemia was highly correlated with HRI in adult Korean representative sample data. Hyperuricemia was associated with a nearly tripled risk for HRI. Hypertension has a synergistic effect with hyperuricemia on HRI. Further research is warranted to clarify the relationship between hyperuricemia and arrhythmia and its mechanism.

Characteristics and outcomes of rheumatoid arthritis patients who started biosimilar infliximab.

To compare the characteristics of rheumatoid arthritis (RA) patients receiving either biosimilar or originator infliximab and to identify the effectiveness and safety of biosimilar infliximab in RA patients in real-world practice. RA patients who started either biosimilar or originator infliximab were selected using the prospective biologic disease-modifying anti-rheumatic drugs (DMARDs) registry: BIOlogics Pharmacoepidemiologic StudY (BIOPSY). Baseline characteristics of the two groups were compared, and short-term treatment outcomes, including DAS28-ESR and HAQ-DI scores, were compared after initiation of biosimilar or originator infliximab. The drug retention rates of the two groups were also compared. A total of 100 RA patients, 55 biosimilar, and 45 originator infliximab users were included in this analysis. Baseline characteristics of age, disease duration, and previous or current medications were similar in the two groups. Baseline DAS28-ESR was higher in the originator infliximab group (6.3 ± 1.1 vs. 5.8 ± 1.1, p = 0.02). The early DAS28-ESR remission rates observed 7.9 ± 1.8 months after starting biosimilar and originator infliximab were 15.0 and 25.0%, respectively (p = 0.47). The change in HAQ-DI did not differ between the two groups (0.4 ± 0.7 vs. 0.4 ± 0.8, p = 0.94). Patients treated with biosimilar infliximab in clinical practice had lower disease activity at the start of treatment than those receiving originator infliximab. Biosimilar infliximab was well-tolerated, safe, and of similar clinical effectiveness to originator infliximab. Larger number of patient and longer follow-up data will be needed to confirm the effectiveness and safety of biosimilar infliximab in clinical practice.

What factors affect discordance between physicians and patients in the global assessment of disease activity in rheumatoid arthritis?

OBJECTIVE: To identify the level of agreement between patients with rheumatoid arthritis (RA) and physicians in the global assessment of disease activity and to explore factors influencing their discordance. METHODS: A total of 4368 patients with RA were analyzed from the KORean Observational study Network for Arthritis (KORONA) database. Patients were divided into four subgroups according to difference from their physicians in the assessment of disease activity by substracting physician's visual analog scale (VAS) from patient's VAS as follows: positive discordance group I (10 mm ≤ discordance <25 mm), positive discordance group II (≥25 mm), concordance (<|10| mm), and negative discordance (≤ -10mm). Multinomial logistic regression analysis was performed to identify factors associated with discordance. RESULTS: Only 1350 (29.2%) patients were classified in the concordance group. Positive discordance was found in 52.3% of the patients (n = 2425), with 33.7% (n = 1563) showing marked discordance (≥25 mm). The high disease activity (OR =1.41), gastrointestinal (GI) disease (OR =1.28), pain (OR =1.12), fatigue (OR =1.07) were consistently associated with positive discordance. CONCLUSION: More than half of patients with RA thought their disease more severe than their physicians. In addition to high disease activity, pain, fatigue, and sleep disturbance or GI disease were associated with the discordance between physicians and patients with RA.

Clinical significance of bone marrow hemophagocytosis in adult patients with malignancy and non-malignancy-induced hemophagocytic lymphohistiocytosis.

Bone marrow hemophagocytosis is a frequently observed but not mandatory finding for the diagnosis of hemophagocytic lymphohistiocytosis (HLH). However, the impact of bone marrow hemophagocytosis on the diagnosis of HLH is still not clear in adult patients. Thus, we retrospectively analyzed adult patients with bone marrow hemophagocytosis between 2000 and 2014 to determine its clinical significance. Among 264 patients with bone marrow hemophagocytosis, malignant disorders were the predominant underlying cause (n = 170, 64 %), especially T/NK-cell (n = 88) and B-cell (n = 45) lymphomas compared to infectious disease (48/264, 18 %). The data for HLH-2004 diagnostic criteria was available in 182 patients, and only 29 % (77/264) of patients with ≥ five positive criteria could be diagnosed with HLH. Among the criteria for the diagnosis of HLH, increased serum ferritin (89 %) was more common than hypofibrinogenemia, hypertriglyceridemia, and bicytopenia (<40 %). The median overall survival was worse in patients with malignancy (9.0 months, 95 % confidence interval [CI] 5.6-12.5) than in those with non-malignant disorders (71.8 months, 95 % CI 56.5-87.1, P < 0.001). In patients with malignancy, the overall survival of patients fulfilling the HLH-2004 criteria was significantly worse than patients who did not (P < 0.001). In conclusion, our results suggest that bone marrow hemophagocytosis might be an important finding in the diagnosis of HLH in adult patients. Considering the high incidence of malignancy as a predisposing disorder for HLH, immediate evaluation should be performed in adult patients with bone marrow hemophagocytosis.

Obesity, metabolic abnormality, and knee osteoarthritis: a cross-sectional study in Korean women.

BACKGROUND: This study aimed to analyze the association between knee osteoarthritis and four body size phenotypes defined by the presence or absence of metabolic abnormality and obesity. MEHODS: This was a cross-sectional study using data from 1,549 female participants of the Fifth Korean National Health and Nutrition Examination Survey. Knee osteoarthritis was defined as a Kellgren-Lawrence grade of ≥ 2. Metabolically abnormal state was defined as presence of more than one abnormality among five metabolic risk factors. Obesity was defined using body mass index. Participants were grouped into one of the four body size phenotypes: metabolically healthy normal weight (MHNW), metabolically abnormal but normal weight (MANW), metabolically healthy obesity (MHO), and metabolically abnormal obesity (MAO). RESULTS: The distribution of each body size phenotype was as follows: MHNW 54.7%, MANW 30.7%, MHO 4.3%, and MAO 10.3%. Prevalence of symptomatic knee osteoarthritis was higher in MANW than in MHNW, and in MAO than in MHO. In multivariable analysis, the association between symptomatic knee osteoarthritis and the body size phenotypes was as follows (OR [95% CI]): MHNW 1.00 (reference), MANW 1.54 (1.15-2.07), MHO 1.61 (0.83-3.13), and MAO 3.47 (2.35-5.14). CONCLUSIONS: Obesity showed closest association with knee osteoarthritis when accompanied by metabolic abnormality.

The role of α-defensin-1 and related signal transduction mechanisms in the production of IL-6, IL-8 and MMPs in rheumatoid fibroblast-like synoviocytes.

OBJECTIVES: To investigate the effect of α-defensin-1 on the expression of IL-6, IL-8 and MMPs as well as the signal transduction mechanisms responsible for their expression in RA fibroblast-like synoviocytes (FLS). METHODS: The concentrations of α-defensin-1 in SF were measured by ELISA. In RA FLS, mRNA expression of IL-6, IL-8 and MMPs and activation of signalling molecules were examined by real-time PCR, western blotting and electrophoretic mobility shift assay. RESULTS: Concentrations of SF α-defensin-1 were significantly increased in RA patients compared with OA patients. The levels of mRNA expression of IL-6, IL-8, MMP-1 and MMP-3 were significantly increased in RA FLS treated with α-defensin-1 compared with controls. Furthermore, α-defensin-1 activated JNK and ERK in RA FLS, respectively. Treatment of RA FLS with ERK or JNK inhibitors prior to α-defensin-1 treatment resulted in reduced expression of IL-6, IL-8, MMP-1, and MMP-3 compared with controls. Remarkably, treatment of RA FLS with an ERK inhibitor prior to α-defensin-1 stimulation significantly reduced production of IL-6 and MMP-1 by approximately 71% and 98% compared with controls, respectively. The JNK inhibitor significantly suppressed α-defensin-1-induced MMP-1 production by approximately 73% compared with controls. Finally, there was a significant induction of NF-κB DNA binding activity in response to α-defensin-1. CONCLUSION: Our results suggest that α-defensin-1 may play a role in RA pathogenesis by regulating the production of MMPs as well as IL-6 and IL-8. These processes were dependent on the regulation of the JNK and/or ERK and NF-κB pathways.

CIP2A facilitates apoptotic resistance of fibroblast-like synoviocytes in rheumatoid arthritis independent of c-Myc expression.

The aim of this study is to investigate the effects of CIP2A (Cancerous inhibitor of protein phosphatase 2A) on the apoptosis of RA FLS. Proliferation and apoptotic activity of RA FLS following treatment with CIP2A siRNA or control siRNA were analyzed using MTT assays and Cell Death Detection kit. RA FLS was treated with CIP2A siRNA or control siRNA in 3-, 6-, and 9-day intervals for a Western blot analysis to determine C-Myc expression. To evaluate the signal transduction pathways engaged in apoptosis, caspase-3 activity, caspase-9 activity, PARP, and phosphorylation of the Akt kinase were analyzed by Western blot. Cell viability of RA FLS was significantly lower in the CIP2A siRNA-treated group compared with the control after 7 days (p = 0.022). Apoptosis of RA FLS was significantly higher in the CIP2A siRNA-treated group compared with the control when incubated for 3, 6, and 9 days (p = 0.029, p = 0.021, p = 0.043, respectively). C-Myc expression did not change with the different incubation periods. CIP2A siRNA-treated FLS expressed higher level of activated caspase-3, caspase-9, and PARP (p = 0.014, p = 0.020, p = 0.021, respectively) and lower level of phosphorylated Akt (p = 0.001) compared with those treated with the control siRNA. Our data show that CIP2A expression in RA FLS is an important mediator of dysfunctional apoptosis independent of c-Myc stabilization. Expression of CIP2A may contribute to apoptotic resistance of RA FLS through the activation of Akt and deactivation of caspase-3, caspase-9, and PARP. Inhibition of CIP2A may therefore constitute a novel, promising therapeutic target in RA.

Altered Risk of Incident Gout According to Changes in Metabolic Syndrome Status: A Nationwide, Population-Based Cohort Study of 1.29 Million Young Men.

OBJECTIVE: Few data are available on whether changes in metabolic syndrome affect incident gout. This study was undertaken to assess associations between metabolic syndrome status and incident gout, as well as changes in the clinical characteristics of metabolic syndrome and incident gout, in a cohort of young men. METHODS: This nationwide, population-based cohort study included 20-39-year-old men who participated in serial health check-ups. The outcome, incident gout, was defined according to the claims database diagnostic code for gout. Associations among changes in metabolic syndrome status and incident gout were analyzed using Cox proportional hazards models. RESULTS: Among 1,293,166 individuals, 18,473 were diagnosed as having gout (incidence rate 3.36 per 1,000 person-years). Subjects who had chronic metabolic syndrome (defined as metabolic syndrome at all 3 health check-ups) had a nearly 4-fold higher risk of incident gout compared to subjects who did not have metabolic syndrome at any of the 3 health check-ups (adjusted hazard ratio [HRadj ] 3.82 [95% confidence interval (95% CI) 3.67-3.98]). Development of metabolic syndrome more than doubled the risk of incident gout (HRadj 2.31 [95% CI 2.20-2.43]). Conversely, recovery from metabolic syndrome reduced the risk of incident gout by nearly half (HRadj 0.52 [95% CI 0.49-0.56]). Among metabolic syndrome components, changes in elevated triglycerides (development of elevated triglycerides, HRadj 1.74 [95% CI 1.66-1.81]; recovery from elevated triglycerides, HRadj 0.56 [95% CI 0.54-0.59]) and abdominal obesity (development of abdominal obesity, HRadj 1.94 [95% CI 1.85-2.03]; recovery from abdominal obesity, HRadj 0.69 [95% CI 0.64-0.74]) showed the greatest association with altered risk of incident gout. Associations between changes in the status and clinical characteristics of metabolic syndrome and incident gout were more pronounced in subjects ages 20-29 years compared to those ages 30-39 years, and in subjects who were underweight or who had a normal weight. CONCLUSION: Changes in the status and clinical characteristics of metabolic syndrome were associated with altered risk of incident gout. These results suggest that metabolic syndrome is a modifiable risk factor for gout.

Women with Metabolic Syndrome and Unhealthy Lifestyle Factors Are at a Higher Risk for Hyperuricemia.

Hyperuricemia (HUA) has become a significant medical concern due to its complications and links to metabolic syndrome (MetS) and cardiovascular disease (CVD), which result in increased mortality. The pathogenic processes associated with unhealthy behaviors, MetS, and HUA can be cooperative and potentially synergistic in the activation of risk factors. Recent research has shown sex-based differences in the relationship between HUA and its associated risk factors. This study aimed to investigate these differences, particularly in the context of MetS and CVD risk factors and unhealthy lifestyles. We also aimed to evaluate the joint effects of these factors based on sex. We conducted a cross-sectional study using nationally representative survey data from the Korean National Health and Nutritional Examination Survey 2016-2018. We performed multivariable logistic regression analysis, calculating adjusted odds ratios (ORs) with their 95% confidence intervals (CIs). We also conducted subgroup analyses based on sex and the presence of MetS with or without unhealthy lifestyle factors (tobacco use, alcohol intake). We found sex-based differences in the relationships between HUA and MetS, CVD risk factors, and lifestyle behaviors. Our major finding was a significant association between MetS and HUA in both men and women, regardless of alcohol consumption and smoking status, and this association was stronger in women. We also observed a synergistic effect of MetS and lifestyle factors on the risk of HUA, particularly in women, in whom the risk of HUA increased up to four times compared to the reference group. A sex-based clinical strategy for HUA is necessary to reduce related complications and their socio-economic burden.

Implementation of Systematic Bioanalysis of Antibody-Drug Conjugates for Preclinical Pharmacokinetic Study of Ado-Trastuzumab Emtansine (T-DM1) in Rats.

Antibody-drug conjugates (ADCs) are composed of monoclonal antibodies covalently bound to cytotoxic drugs by a linker. They are designed to selectively bind target antigens and present a promising cancer treatment without the debilitating side effects of conventional chemotherapies. Ado-trastuzumab emtansine (T-DM1) is an ADC that received US FDA approval for the treatment of HER2-positive breast cancer. The purpose of this study was to optimize methods for the quantification of T-DM1 in rats. We optimized four analytical methods: (1) an enzyme-linked immunosorbent assay (ELISA) to quantify the total trastuzumab levels in all drug-to-antibody ratios (DARs), including DAR 0; (2) an ELISA to quantify the conjugated trastuzumab levels in all DARs except DAR 0; (3) an LC-MS/MS analysis to quantify the levels of released DM1; and (4) a bridging ELISA to quantify the level of anti-drug antibodies (ADAs) of T-DM1. We analyzed serum and plasma samples from rats injected intravenously with T-DM1 (20 mg/kg, single dose) using these optimized methods. Based on these applied analytical methods, we evaluated the quantification, pharmacokinetics, and immunogenicity of T-DM1. This study establishes the systematic bioanalysis of ADCs with validated assays, including drug stability in matrix and ADA assay, for future investigation on the efficacy and safety of ADC development.

Lymphomatoid papulosis in a patient treated with adalimumab for juvenile rheumatoid arthritis.

Anti-tumor necrosis factor (TNF) agents are now well regarded as highly effective treatment modalities for multiple immunologically mediated diseases, including rheumatoid arthritis, Crohn's disease and psoriasis. The mechanism of action for this particular class of medications involves the blockade of multiple intracellular signaling pathways originating from TNF-α, ultimately inducing a generalized immunosuppressed state. In fact, several cases of lymphomas have been reported in patients treated with anti-TNF-α agents, though it has been difficult to prove any degree of causality. Herein, we described a patient who developed lymphomatoid papulosis after being treated with adalimumab, whereby a clear causality could be established.

A case of ANCA-associated vasculitis presenting with calf claudication.

Wegener's granulomatosis (WG), Churg-Strauss syndrome, and microscopic polyangiitis (MPA) are closely related small vessel vasculitides characterized by anti-neutrophil cytoplasmic antibodies (ANCA). Although there were some reports of MPA presenting with claudication, there are very few reports on WG presenting with claudication of calf muscles. We report an unusual case of ANCA-associated vasculitis in a 75-year-old man who presented with bilateral calf claudication. Comprehensive evaluations, including electromyography, nerve conduction study, lower extremity magnetic resonance imaging, and Doppler scan, did not reveal any other cause of bilateral calf claudication. P-ANCA and anti-myeloperoxidase antibody was positive, but the anti-proteinase 3 antibody was negative. Chest computed tomography scan showed subpleural honeycombing and reticulation, predominantly in both basal lung areas. Biopsy of the calf muscle showed granulomatous vasculitis. Kidney biopsy was also performed which revealed focal necrotizing glomerulonephritis. Our patient does not exhibit typical clinical features for WG, but histopathologic findings of necrotizing granulomatous vasculitis in calf muscle biopsy is highly suggestive of WG.

Clinical features and outcome of microscopic polyangiitis under a new consensus algorithm of ANCA-associated vasculitides in Korea.

The classification system for antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis and polyarteritis nodosa had its limitations due to numerous overlapping features of these disease entities. The aim of this study is to investigate the clinical features and outcome of patients diagnosed with microscopic polyangiitis (MPA) according to the newly proposed consensus algorithm of ANCA-associated vasculitides and polyarteritis nodosa. Fifty-five cases of MPA, comprised of 33 men and 22 women, diagnosed according to a new consensus algorithm at a single tertiary hospital were identified for analysis. The main clinical features were constitutional symptoms (78.2%), followed by renal involvement (74.5%), musculoskeletal symptoms (67.3%), skin manifestations (50.9%), neurologic involvement (43.6%), and lung involvement (41.8%). P-ANCA and/or anti-myeloperoxidase antibody were present in 69.1%. Five Factor Score and Birmingham Vasculitis Activity Score (BVAS) at diagnosis were 1.1 ± 0.9 and 10.9 ± 4.9, respectively. Forty-four patients were available for a long-term follow-up, and six patients (13.6%) resulted in death. Mortality was associated with BVAS > 9 at the time of diagnosis, age > 60 years, and presence of cardiomyopathy and interstitial lung disease. The survival rate at 1 and 3 years was 93.9 and 89.2%, respectively. Eight patients (14.5%) required dialysis at the time of diagnosis. This is the first study to demonstrate the clinical features in patients with MPA using a new consensus algorithm. Survival rate was higher than previously reported, and interstitial lung disease was a new risk factor for death in patients with MPA.

Outcome of reclassification of World Health Organization (WHO) class III under International Society of Nephrology-Renal Pathology Society (ISN-RPS) classification: retrospective observational study.

The outcome of systemic lupus erythematosus (SLE) is largely influenced by the existence of lupus nephritis (LN), and its histologic classification guides the treatment and prognosis of SLE. International Society of Nephrology-Renal Pathology Society (ISN-RPS) announced a revised classification of LN in 2004. The present study investigated the differential outcome of World Health Organization (WHO) class III LN when reclassified according to ISN-RPS classification. Forty-three patients with biopsy-proven WHO class III LN at a single tertiary hospital were included in the study. Baseline characteristics at the time of renal biopsy and clinical data during follow-up were obtained from medical records. Renal response to treatment at one-year follow-up was analyzed in three ways; complete response (CR), partial response (PR), and no response (NR). Of 43 patients with previous WHO class III LN, 12 cases were reclassified into ISN-RPS class IV (9 cases of class IV-S and 3 cases of IV-G). Baseline characteristics at the time of renal biopsy were not different between the reclassified class IV and remaining class III LN group except activity index on renal histology, which was significantly elevated in the reclassified class IV group (4.90 vs. 6.75; P = 0.02). Significantly higher number of patients with remaining class III LN achieved CR to treatment than those with reclassified class IV LN at one-year follow-up since initial biopsy (CR: PR: NR; 16:7:7 vs. 3:1:8; P = 0.032). Our study suggests that the ISN-RPS classification is more advantageous in predicting renal outcome and guiding treatment when evaluating previously classified WHO class III LN.

CIP2A expression is associated with synovial hyperplasia and invasive function of fibroblast-like synoviocytes in rheumatoid arthritis.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that leads to cellular proliferation in cancer cells. We aim to investigate CIP2A expression in fibroblast-like synoviocytes (FLS) and its association with the histopathological grade of synovitis and the invasive function of FLS in rheumatoid arthritis (RA). CIP2A protein expression was measured in 8 RA FLS and 8 OA FLS using Western blot analysis. CIP2A mRNA expression from 19 RA FLS and 7 OA FLS was measured using real-time PCR. Synovitis score of RA FLS-matched synovial tissues was semiquantitatively measured by two independent pathologists. An in vitro cell invasion assay was performed using RA FLS treated with CIP2A small interfering RNA (siRNA) or with control vector. Western blot analysis showed that CIP2A is more frequently overexpressed in RA FLS compared with OA FLS. CIP2A mRNA expression was higher in RA FLS compared with those in OA FLS, but did not reach statistical significance (P = 0.076). In RA, total synovitis score was strongly correlated with FLS CIP2A mRNA expression (rs = 0.849, P = 0.043). TNF-α treatment induced a robust increase in the invasive function of control FLS (P = 0.0021), but no significant effect was observed in CIP2A siRNA-treated FLS. Our data demonstrate that CIP2A expression is closely associated with the histopathological score of synovitis and invasive function of FLS in RA. These results suggest that CIP2A may play a critical role in the destructive process in RA and warrant further investigation of CIP2A as a therapeutic target.

Correlation of DEFA1 gene copy number variation with intestinal involvement in Behcet's disease.

Copy number variation has been associated with various autoimmune diseases. We investigated the copy number (CN) of the DEFA1 gene encoding α-defensin-1 in samples from Korean individuals with Behcet's disease (BD) compared to healthy controls (HC). We recruited 55 BD patients and 35 HC. A duplex Taqman® real-time PCR assay was used to assess CN. Most samples (31.1%) had a CN of 5 with a mean CN of 5.4 ± 0.2. There was no significant difference in the CN of the DEFA1 gene between BD patients and HC. A high DEFA1 gene CN was significantly associated with intestinal involvement in BD patients. Variable DEFA1 gene CNs were observed in both BD patients and HC and a high DEFA1 gene CN may be associated with susceptibility to intestinal involvement in BD.

Prevalence of rheumatoid factor and parameters associated with rheumatoid factor positivity in Korean health screening subjects and subjects with hepatitis B surface antigen.

OBJECTIVES: The purpose of this study is to assess the prevalence and titer of rheumatoid factor (RF) in Korean health screening subjects and consecutive subjects with hepatitis B surface antigen (HBsAg) and to examine the factors influencing RF positivity. METHODS: This study was performed in 37,660 patients (23,269 men, 14,391 women) without arthralgia, who participated in a health checkup program in 2009. RESULTS: Approximately 3.7% of health screening subjects (3.3% of males and 4.4% of females) were positive for RF. Among subjects with HBsAg (n = 1,494) and antibody for hepatitis C virus (HCV) (n = 132), 11.8 and 10.6% were RF positive, respectively. There was a significant difference in the RF-positive rate between males and females. The RF-positive rate had a significant linear-by-linear association with aging, but there was no significant relationship between RF positivity and aging among subjects with HBsAg or anti-HCV antibody. Presence of HBsAg and anti-HCV antibody, positive C-reactive protein (CRP), and female sex were factors strongly associated with RF positivity. CONCLUSIONS: The rate of RF positivity in health screening adults and subjects with HBsAg in Korea can be estimated to be 3.7 and 11.8%, respectively. Clinicians should consider hepatitis B or C virus infection status, CRP positivity, and sex when interpreting RF-positive results.

Increased risk of malignancy in patients with Takayasu's arteritis: a population-based cohort study in Korea.

This study aimed to evaluate the relative risk of malignancy in patients with Takayasu's arteritis compared to that in the general population. This retrospective nationwide cohort study used data from the Korean Health Insurance Review and Assessment Service database. All newly diagnosed patients with Takayasu's arteritis were identified between January 2009 and December 2019. They were observed until the diagnosis of malignancy, death, or end of the observational period, December 2020. The standardized incidence ratios (SIRs) of the overall and site-specific malignancies were estimated and compared with the incidence of cancer in the general population retrieved from the National Cancer Registry. We identified 1449 newly diagnosed patients with Takayasu's arteritis during the observational period (9196 person-years). A total of 74, 66, and 8 patients had overall, solid, and hematologic malignancies, respectively. The risks of overall [SIR, 1.62; 95% confidence interval (CI) 1.27-2.03], solid (SIR, 1.51; 95% CI 1.17-1.92), and hematologic (SIR, 4.05; 95% CI 1.75-7.98) malignancies were increased compared to those in the general population. In solid malignancies, breast (SIR, 2.07; 95% CI 1.16-3.42) and ovarian (SIR, 4.45; 95% CI 1.21-11.39) cancers had an increased risk. In hematologic malignancies, the risk of myelodysplasia increased (SIR, 18.02; 95% CI 3.72-52.66). Immunosuppressive agent use was not associated with malignancy. There was no specific period when cancer more frequently occurred. An increased risk of malignancy was observed in patients with Takayasu's arteritis compared to that in the general population in this large-scale nationwide population study of Korean health insurance data.