Geun-Tae Kim

Interleukin 17 (IL-17) Increases the Expression of Toll-like Receptor-2, 4, and 9 by Increasing IL-1β and IL-6 Production in Autoimmune Arthritis

Objective. To examine the effect of interleukin 17 (IL-17) on the expression of Toll-like receptor (TLR)-2, 4, and 9 in collagen-induced arthritis (CIA) in mice. Methods. On Days 28 and 32 after induction of CIA in mice, phosphate-buffered saline (PBS group) or IL-17 (IL-17 group) was injected into both knee joints. On Day 35, mice were sacrificed. The severity of knee joint arthritis, synovial inflammation, and bone destruction was measured by a scoring system using macrography and histological analysis. Synovial expression of TLR-2, 4, 9, IL-17, IL-1ß, tumor necrosis factor-α (TNF-α), and IL-6 was determined by real-time PCR and immunohistochemistry. Synoviocytes of CIA mice were cultured with IL-17 and with neutralizing antibodies to cytokine, and the expression of TLR-2, 4, 9, IL-1ß, TNF-α, and IL-6 was determined by real-time RT-PCR. Results. In CIA mice, knee arthritis scores, synovial inflammation, bone destruction scores, and expression of synovial TLR-2, 4, and 9, IL-17, IL-1ß, TNF-α and IL-6 were higher in the IL-17 and PBS groups than in normal DBA1 mice. These variables were also significantly higher in the IL-17 group than in the PBS group. In CIA synoviocytes, IL-17 increased the expression of TLR-2, 4, and 9, and this effect was significantly alleviated by neutralizing antibodies to IL-17, IL-1ß, and IL-6. Conclusion. IL-17 aggravates joint inflammation and destruction, and increases the synovial expression of TLR-2, 4, and 9 by increasing IL-1ß and IL-6. These results imply that the IL-17-induced increase in expression of TLR-2, 4, and 9, and IL-1ß and IL-6 production are involved in the IL-17-induced aggravation of arthritis.

Increased frequency of osteoporosis and BMD below the expected range for age among South Korean women with rheumatoid arthritis

To compare the frequency of osteoporosis and bone mineral density (BMD) below the expected range for age between female patients with rheumatoid arthritis (RA) and healthy subjects and to determine risk factors for bone loss in female patients with RA.

IL-32 aggravates synovial inflammation and bone destruction and increases synovial natural killer cells in experimental arthritis models

This study was performed to investigate the effects of IL-32 on joint inflammation, bone destruction, and synovial cytokine expressions, and on synovial natural killer (NK) cell expressions in collagen-induced arthritis (CIA). CIA was induced by type II collagen in DBA1 mice, and phosphate-buffered saline (PBS group) or IL-32 (IL-32 group) were injected into both knee joints at day 28 and 32, then mice were killed at day 35. Severity of synovial inflammation and bone destruction was determined by histological scoring method, and synovial cytokine expressions such as IL-1β, TNF-α, IL-17, IL-18, IFN-γ, IL-21, and IL-23 were measured by real-time RT-PCR and western blot. Synovial NK cell expressions were determined by real-time RT-PCR, western blot and immunohistochemistry, and chemokines and chemokine receptors expressions that are associated with NK cell migration were determined by real-time RT-PCR. Scores of synovial inflammation and bone destruction, synovial expressions of IL-1β, TNF-α, IL-18, and IFN-γ were significantly increased in IL-32 group compared with PBS group. Synovial expressions of NK cell, and chemokines (CCL2 and CXCL9) and chemokine receptors (CCR2 and CCR5) that are associated with NK cell migration were significantly increased in IL-32 group compared with PBS group. IL-32 aggravated joint inflammation and bone destruction and increased synovial expressions of inflammatory cytokine and NK cells in CIA. These results suggest that IL-32 play a role in joint inflammation and bone destruction, and IL-32 might be a new target for treatment of rheumatoid arthritis.

IL-17 increases cadherin-11 expression in a model of autoimmune experimental arthritis and in rheumatoid arthritis.

IL-17 plays important roles in synovial inflammation and bone destruction in the mouse model of autoimmune arthritis and in rheumatoid arthritis (RA). Cadherin-11 determines the behavior of synovial cells in their proinflammatory and destructive tissue response in inflammatory arthritis, and promotes the invasive behavior of fibroblast-like synoviocytes (FLS). The purpose of this study was to examine the effect of IL-17 on the expression of cadherin-11 in autoimmune experimental arthritis and in RA synovium. The severity of synovial inflammation and bone destruction were examined in IL-17-injected knee joints of mice with collagen-induced arthritis (CIA). Cadherin-11 expression was examined in the synovium of mice with CIA, of IL-1 receptor antagonist (IL-1Ra)-deficient mice and of patients with RA and osteoarthritis (OA). Cadherin-11 expression was also examined in the synovium of IL-17 injected knee joints from CIA mice and in IL-17-stimulated FLS of CIA mice and RA patients. IL-17 aggravated synovial inflammation and bone destruction in CIA. By immunohistochemistry, cadherin-11 expression was increased in the synovium of mice with CIA and IL-1Ra-deficient mice and in patients with RA. Synovial cadherin-11 expression in IL-17-injected knee joints, measured by real-time RT-PCR, Western blot and immunohistochemistry, was increased in CIA. Cadherin-11 expression was significantly increased by IL-17 in cultured FLS of CIA mice and RA patients, and these increases were blocked by NF-κB inhibitors. IL-17 increased the expression of cadherin-11 in vivo and in vitro, which implies that an IL-17-induced increase of cadherin-11 is involved in IL-17-induced aggravation of joint destruction and inflammation.

Drug survival and the associated predictors in South Korean patients with rheumatoid arthritisreceiving tacrolimus

Background/Aims To investigate the drug survival rate of tacrolimus (TAC) and analyze the potential predictors of this rate in patients with rheumatoid arthritis (RA) in routine care. Methods2018-01-16 In this retrospective longitudinal study, we enrolled 102 RA patients treated with TAC from April 2009 to January 2014 at a tertiary center in South Korea. The causes of TAC discontinuation were classified as lack of efficacy (LOE), adverse events (AEs), and others. The drug survival rate was estimated using the Kaplan-Meier method and the predictors of this rate were identified by Cox-regression analyses. Results TAC was discontinued in 27 of 102 RA patients (26.5%). The overall 1-, 2-, 3-, and 4-year TAC continuation rates were 81.8%, 78.4%, 74.2%, and 69.1%, respectively and the median follow-up period from the start of TAC was 32.5 months. The number of TAC discontinuations due to LOE, AEs, and others were 15 (55.6%), 11 (40.7 %), and 1 (3.7%), respectively. The baseline high disease activity was a significant risk factor for TAC discontinuation after adjusting for confounding factors (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.16 to 5.35; p = 0.019). In addition, underlying interstitial lung disease was significantly associated with TAC withdrawal due to AEs (HR, 3.49; 95% CI, 1.06 to 11.46; p = 0.039). Conclusions In our study, TAC showed a good overall survival rate in patients with RA in real clinical practice. This suggests that the long-term TAC therapy has a favorable efficacy and safety profile for treating RA.

Intravertebral vacuum cleft sign: a cause of vertebral cold defect on bone scan

A 67-year-old female presented with an acute compression fracture with an intravertebral vacuum cleft (IVC) sign of the T12 vertebra. Her bone scan demonstrated a cold defect of the fractured vertebra. Although the IVC sign is related to vertebral osteonecrosis, to the best of our knowledge, a cold defect on a bone scan has not been reported in an acute compression fracture with an IVC sign. In this case review, various imaging findings of osteonecrotic compression fractures are discussed along with a review of the current literature.

Evaluation of an Automated Screening Assay, Compared to Indirect Immunofluorescence, an Extractable Nuclear Antigen Assay, and a Line Immunoassay in a Large Cohort of Asian Patients with Antinuclear Antibody-Associated Rheumatoid Diseases: A Multicenter Retrospective Study

We assessed the diagnostic utility of the connective tissue disease (CTD) screen as an automated screening test, in comparison with the indirect immunofluorescence (IIF), EliA extractable nuclear antigen (ENA), and line immunoassay (LIA) for patients with antinuclear antibody- (ANA-) associated rheumatoid disease (AARD). A total of 1115 serum samples from two university hospitals were assayed using these four autoantibody-based methods. The AARD group consisted of patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögrens syndrome (SS), and mixed connective tissue disease (MCTD). The qualitative results of all four autoantibody assays showed a significant association with AARDs, compared to controls (P < 0.0001 for all). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for differentiating total AARDs, SLE, SSc, SS, and MCTD from controls were 0.89, 0.93, 0.73, 0.93, and 0.95, respectively. The ROC-AUCs of combination testing with LIA were slightly higher in patients with AARDs (0.92) than those of CTD screen alone. Multivariate analysis indicated that all four autoantibody assays could independently predict AARDs. CTD screening alone and in combination with IIF, EliA ENA, and LIA are potentially valuable diagnostic approaches for predicting AARDs. Combining CTD screen with LIA might be effective for AARD patients.

Acute exacerbation of ankylosing spondylitis after chlamydial infection in a patient well-controlled with etanercept.

Dear Editor, We would like to report a case of ankylosing spondylitis that was acutely exacerbated after chlamydial infection. A 26-year-old man was admitted to the hospital complaining of ocular pain and left ankle arthralgia. Five years prior, he had been diagnosed with ankylosing spondylitis. His ankylosing spondylitis symptoms had been well-controlled with etanercept and methotrexate (MTX) for the 2 years prior to admission. One week before admission, he had experienced abrupt onset of ocular pain, left ankle arthralgia and swelling (Fig. 1a). Although we were unable to identify specific aggravating factors in the patient’s history, he reported intermittent voiding discomfort after having sex with a prostitute about 6 weeks prior to admission. In the patient’s previous laboratory tests, human leukocyte antigen (HLA)-B27 was positive. Representative laboratory values on admission to the hospital showed leukocyte count of 13 400/mm (normal: 4000–10 000/mm), C-reactive protein was 6.8 mg/dL (normal < 0.5 mg⁄dL), and erythrocyte sediment rate 85 mm/h (normal < 20 mm/h). Markers of hepatitis B, C, VDRL (syphilis test), and human immunodeficiency virus were all negative. In urine analysis, leukocytes were 10–15/high power field. Blood and urine cultures were negative, but urine Chlamydia trachomatis polymerase chain reaction was positive. Musculoskeletal ultrasound revealed joint effusion and tenosynovitis in the left ankle (Fig. 1b,c), so we performed ultrasound-guided aspiration. Acid-fast bacilli stain, Gram stain and culture results of the patient’s joint fluid were negative. Ophthalmic examination showed severe anterior uveitis of both eyes (Fig. 2). On admission, we were unable to rule out infectious diseases based on initial laboratory results and therefore initiated broad-spectrum antibiotic therapy, 60 mg/day of prednisolone for severe uveitis and sulfasalazine, non-steroidal anti-inflammatory drugs (NSAIDs) and MTX for arthritis. The patient’s etanercept regimen was