Joong Kyong Ahn

Korean Observational Study Network for Arthritis (KORONA): Establishment of a Prospective Multicenter Cohort for Rheumatoid Arthritis in South Korea

OBJECTIVESnThe object of this study was to introduce the KORean Observational study Network for Arthritis (KORONA) registry with an emphasis on the design of the Korean rheumatoid arthritis (RA) national database, as well as to provide an overview of the RA patients who are currently registered in KORONA.nnnMETHODSnThe KORONA was established in July 2009 by the Clinical Research Center for Rheumatoid Arthritis (CRCRA) in South Korea. KORONA is based on a prospective protocol and standard, defined data collection instruments. Demographic and clinical features, laboratory and radiologic data, health-related outcomes, treatment side effects, resource utilization, and health behaviors of the RA cohort patients are recorded in a database.nnnRESULTSnA total of 23 institutions, which are about 38% of the rheumatologic departments at tertiary academic hospitals across South Korea, are part of KORONA. The quality control of data collection and management has been performed through annual monitoring and auditing, staff training, and providing standard operation protocol by the executive committee of CRCRA. As of 31 December 2010, 4721 patients with established RA were included in KORONA, because an annual survey had started to be performed in July 2010.nnnCONCLUSIONSnKORONA is the first nationwide Korean RA-specific cohort and it will provide valuable real-world information for Korean RA patients.

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

OBJECTIVESnTo 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).nnnMETHODSnThe 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.nnnRESULTSnConcentrations 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.nnnCONCLUSIONnOur 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.

Behcet’s disease associated with malignancy in Korea: a single center experience

The aim of this study was to determine the clinical characteristics of Behcet’s disease (BD) complicated with malignancy in Korea. Of 1,769 patients with BD in our hospital, 32 patients (1.8%, 21 in solid cancer, 11 in hematologic malignancy) developed cancer. In 10 of the 32 subjects (31.3%), malignancy was diagnosed before or concomitantly with BD. Twelve cases (37.5%) occurred within the first 2xa0years of disease and 9 cases (28.1%) occurred 5xa0years after the diagnosis of BD. Myelodysplastic syndrome (MDS) was the most common disease (nxa0=xa07) followed by thyroid cancer (nxa0=xa04), breast cancer, cervix cancer, stomach cancer, rectal cancer, hepatoma, aplastic anemia (nxa0=xa03, each), renal cell cancer, endometrial cancer, lymphoma (nxa0=xa01, each). There were no significant differences in the clinical characteristic between patients with or without malignancy. Intestinal involvement were more frequent in patients with malignancy than those without, but was not statistically significant (pxa0=xa00.083). Our results demonstrate that MDS and thyroid cancer are the most common hematologic disease and solid cancer associated with BD, respectively. Further studies will be required to ascertain the pathogenic link between BD and malignancy and the prevalence of malignancy in BD.

Slug suppression induces apoptosis via Puma transactivation in rheumatoid arthritis fibroblast-like synoviocytes treated with hydrogen peroxide

Inadequate apoptosis contributes to synovial hyperplasia in rheumatoid arthritis (RA). Recent study shows that low expression of Puma might be partially responsible for the decreased apoptosis of fibroblast-like synoviocytes (FLS). Slug, a highly conserved zinc finger transcriptional repressor, is known to antagonize apoptosis of hematopoietic progenitor cells by repressing Puma transactivation. In this study, we examined the expression and function of Slug in RA FLS. Slug mRNA expression was measured in the synovial tissue (ST) and FLS obtained from RA and osteoarthritis patients. Slug and Puma mRNA expression in FLS by apoptotic stimuli were measured by real-time PCR analysis. FLS were transfected with control siRNA or Slug siRNA. Apoptosis was quantified by trypan blue exclusion, DNA fragmentation and caspase-3 assay. RA ST expressed higher level of Slug mRNA compared with osteoarthritis ST. Slug was significantly induced by hydrogen peroxide (H2O2) but not by exogenous p53 in RA FLS. Puma induction by H2O2 stimulation was significantly higher in Slug siRNA-transfected FLS compared with control siRNA-transfected FLS. After H2O2 stimulation, viable cell number was significantly lower in Slug siRNA-transfected FLS compared with control siRNA-transfected FLS. Apoptosis enhancing effect of Slug siRNA was further confirmed by ELISA that detects cytoplasmic histone-associated DNA fragments and caspase-3 assay. These data demonstrate that Slug is overexpressed in RA ST and that suppression of Slug gene facilitates apoptosis of FLS by increasing Puma transactivation. Slug may therefore represent a potential therapeutic target in RA.

Drug survival of tumor necrosis factor α inhibitors in patients with ankylosing spondylitis in Korea.

Background/Aims To evaluate drug survival of the tumor necrosis factor α inhibitors (TNFi) and risk factors for the drug discontinuation in patients with ankylosing spondylitis (AS). Methods We retrospectively evaluated 487 AS patients at a single tertiary hospital. Among the TNFi users, drug survival and risk factors of TNFi discontinuation were investigated. Results Among 487 patients, 128 AS patients were treated with at least one TNFi. Patients who were treated with TNFi were younger at disease onset, had more peripheral manifestations, and had higher level of acute phase reactants and body mass index than those of TNFi non-users at baseline. Of 128 patients, 28 patients (21.9%) discontinued first TNFi therapy during the follow-up period of 65.1 ± 27.9 months. In the multivariable analysis, female (hazard ratio [HR], 6.08; 95% confidence interval [CI], 2.27 to 16.27; p = 0.003), hip involvement (HR, 2.52; 95% CI, 1.08 to 5.87; p = 0.033) and a high C-reactive protein (CRP; HR, 1.10; 95% CI, 1.00 to 1.21; p = 0.044) were risk factors for drug discontinuation. Etanercept showed better survival rate than infliximab. The main reason for discontinuation of TNFi was inefficacy. Conclusions TNFi discontinuation rate of Korean patients with AS seems to be similar to those with the European patients. Female sex, hip involvement, CRP, and the type of TNFi were associated with TNFi discontinuation.

Decline of Pulmonary Function Is Associated With the Presence of Rheumatoid Factor in Korean Health Screening Subjects Without Clinically Apparent Lung Disease: A Cross-Sectional Study.

AbstractAlthough higher-than-normal levels of rheumatoid factor (RF) are often observed in subjects without specific medical problems, little is known about the influence of RF on pulmonary function in health screening subjects. This study aimed to determine the association between the presence of RF and decreased pulmonary function in Korean health screening subjects without any history of joint disease or clinically apparent lung disease.A total of 115,641 study subjects (age range, 18–88 years) participated in the health checkup program. We excluded subjects who did not have pulmonary function test, as well as those with abnormal chest radiographs. Subjects with medical history of arthritis including rheumatoid arthritis, and lung disease based on the self-reported questionnaire. Final analysis was performed on 94,438 Koreans (41,261 women).RF-positive subjects had a lower forced vital capacity (FVC) predicted value and forced expiratory volume in 1 s (FEV1) predicted value than RF-negative subjects (82.8u200a±u200a11.5% vs 83.8u200a±u200a11.4% for FVC% predicted and 83.5u200a±u200a13.0% vs 85.1u200a±u200a12.9% for FEV1% predicted, Pu200a<u200a0.001 for both). RF positivity was significantly associated with the decline of FEV1% predicted regardless of smoking history (adjusted odds ratio [OR] = 1.289 [95% confidence interval [CI] 1.163–1.429], Pu200a<u200a0.001 for nonsmokers and adjusted OR = 1.138 [95% CI 1.004–1.289], Pu200a<u200a0.001 for smokers) while the decline of FVC% predicted only in nonsmokers (adjusted OR = 1.251 [95% CI 1.133–1.382], Pu200a<u200a0.001). Our results suggest that the presence of RF could impact pulmonary function in apparently healthy subjects. A follow-up study to investigate serial changes in pulmonary function may reveal the actual influence of raised RF titers.

Predictive factors of radiographic progression in ankylosing spondylitis

Background/Aims The course of ankylosing spondylitis (AS) is rather variable, and the factors that predict radiographic progression remain largely obscure. In this study, we tried to determine the clinical factors and laboratory measures that are useful in predicting the radiographic progression of patients with AS. Methods In 64 consecutive patients with AS, we collected radiographic and laboratory data over 3 years. Radiographic data included images of the sacroiliac (SI) and hip joints and laboratory data included areas under the curve (AUC) of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), alkaline phosphatase (ALP), and hemoglobin (Hb). We investigated associations among changes in radiographic scores, initial clinical manifestations and laboratory measurements. Results Changes in scores for the SI joint and lumbar spine did not correlate with AUC for ESR, CRP, or ALP. AUC for Hb did not significantly correlate with radiographic progression in any joint. Patients with hip arthritis at the initial visit showed significantly higher radiographic score changes after 3 years in the SI and hip joint compared to those without hip arthritis. Patients who had shoulder arthritis as the initial manifestation had significantly increased AUCs for ESR and CRP compared to those without shoulder arthritis. However, at 3 years, the change of the lumbar spine score was significantly higher in patients without shoulder arthritis. Conclusions These results indicate that hip arthritis at presentation is a useful clinical marker for predicting the structural damage to the SI and hip joint, and suggest that initial shoulder arthritis correlates with slower radiographic progression of the lumbar spine.