Tsung-Yun Hou

Usefulness of human leucocyte antigen-B27 subtypes in predicting ankylosing spondylitis: Taiwan experience

Background:  Genetic factors are clearly attributed to the susceptibility of ankylosing spondylitis (AS). The human leucocyte antigen (HLA)‐B27 proved to be the very useful marker for diagnosing AS. The aim of this study was to determine the prevalence of HLA‐B27 subtypes in Taiwan and to investigate whether these subtypes may be of help in predicting the diagnosis of AS.

Retinoid Acid Inhibits IL-1-Induced iNOS, COX-2 and Chemokine Production in Human Chondrocytes

This study aims to investigate the effects and mechanisms of all-trans retinoic acid (t-RA) on interleukin(IL)-1-induced production of several inflammatory mediators in human chondrocytes. The cartilage from OA patients receiving total knee or total hip replacement was obtained and chondrocytes were prepared. Chemokine concentrations were measured by ELISA. The expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was determined by Western blotting and/or RT/PCR. Nitrite levels were measured by Griess assays. The DNA-binding activity and transcriptional activity of activator protein-1 (AP-1) were measured by electrophoresis mobility shift assay and luciferase assay. We showed that t-RA suppressed IL-1-induced release of chemokines, including regulated upon activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein 2 (MCP-2), macrophage inflammatory protein-1alpha (MIP-1α) and MIP-1β. Four different retinoid derivatives all preserved inhibitory effects albeit the potency was different. t-RA potently suppressed IL-1-induced expression of iNOS and COX-2 and production of nitric oxide and prostaglandin E2. In consistent with the results in primary chondrocytes, t-RA down-regulated IL-1-induced AP-1 DNA binding activity and transcriptional activity in a human fibroblast-like (commercially labeled as chondrocyte) cell line. By examining the effect of a c-jun N-terminal kinase (JNK) specific inhibitor, we showed that the suppression of JNK-AP-1 signaling was enough to inhibit IL-1-induced production of chemokines and activation of iNOS and COX-2 pathways. Collectively, our results raise a therapeutic option that intra-articular administration of retinoid derivatives at 10–1000 nanomolar concentrations may be effective to suppress the progression of inflammatory OA.

Ginkgo biloba Extract Individually Inhibits JNK Activation and Induces c-Jun Degradation in Human Chondrocytes: Potential Therapeutics for Osteoarthritis

Osteoarthritis (OA) is a common joint disorder with varying degrees of inflammation. The ideal anti-OA drug should have immunomodulatory effects while at the same time having limited or no toxicity. We examined the anti-inflammatory effects of Ginkgo biloba extract (EGb) in interleukin-1 (IL-1)-stimulated human chondrocytes. Chondrocytes were prepared from cartilage specimens taken from patients with osteoarthritis who had received total hip or total knee replacement. The concentrations of chemokines and the degree of cell migration were determined by ELISA and chemotaxis assays, respectively. The activation of inducible nitric oxide synthase (iNOS), mitogen-activated protein kinases (MAPKs), activator protein-1 (AP-1), and nuclear factor-kappaB (NF-κB) was determined by immunoblotting, immunohistochemistry, and electrophoretic mobility shift assay. We found that EGb inhibited IL-1-induced production of chemokines, which in turn resulted in attenuation of THP-1 cell migration toward EGb-treated cell culture medium. EGb also suppressed IL-1-stimulated iNOS expression and release of nitric oxide (NO). The EGb-mediated suppression of the iNOS-NO pathway correlated with the attenuation of activator protein-1 (AP-1) but not nuclear factor-kappaB (NF-κB) DNA-binding activity. Of the mitogen-activated protein kinases (MAPKs), EGb inhibited only c-Jun N-terminal kinase (JNK). Unexpectedly, EGb selectively caused degradation of c-Jun protein. Further investigation revealed that EGb-mediated c-Jun degradation was preceded by ubiquitination of c-Jun and could be prevented by the proteosome inhibitor MG-132. The results imply that EGb protects against chondrocyte degeneration by inhibiting JNK activation and inducing ubiquitination-dependent c-Jun degradation. Although additional research is needed, our results suggest that EGb is a potential therapeutic agent for the treatment of OA.

Purtscher’s-like retinopathy as an initial presentation of adult-onset Still’s disease: a case report and review of the literature

Adult-onset Still’s disease is a multisystem inflammatory disorder of unknown etiology and is characterized by high, spiking fever, arthritis, evanescent maculopapular rash, myalgia, serositis, leukocytosis, and involvement of various organs including the eyes. The ocular manifestations have been described including orbital pseudotumor, ptosis, and diplopia with orbital pain but never Purtscher’s-like retinopathy. We describe a 21-year-old male patient with adult-onset Still’s disease who developed the Purtscher’s-like retinopathy. To our knowledge, this is the first reported adult-onset Still’s disease patient with Purtscher’s-like retinopathy as the initial presentation.

Remitting seronegative symmetrical synovitis with pitting edema following acute intracranial hemorrhage

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is an unusual inflammatory arthritis with unknown pathogenic mechanism, and is characterized by an acute onset of symmetrical synovitis with pitting edema of the hands or feet. Numerous diseases are associated with RS3PE, including neoplasia, infection, Parkinson’s disease, and other rheumatic diseases. Neoplasia is the most common condition associated with RS3PE. We report a case of RS3PE that occurred following acute intracranial hemorrhage in an 80-year-old man with a 20-year history of hypertension.

A Comparison of the Diagnostic Sensitivity and Specificity of Two Anti-cyclic Citrullinated Peptides (CCP1 and CCP2) Tests for Rheumatoid Arthritis

The detection of anti-cyclic citrullinated peptide (CCP) autoantibodies has been considered a useful tool to identify rheumatoid arthritis (RA) patients. Here, we examined the sensitivity and specificity of two detection methods, namely the ELISA-based (anti-CCP1) and the EliA-based (anti-CCP2) for anti-CCP in 40 RA patients. Methods. Anti-CCP1 and anti-CCP2 antibody tests were performed on 79 patients with arthropathy. The sensitivity, specificity, positive predictive value, and negative predictive value for-discriminating between rheumatoid arthritis (RA) and non-RA were calculated for both tests. Results. Both anti-CCP1 and anti-CCP2 shared very similar specificities (97.4%) toward diagnosing RA. However, there was no significant associations between the titer of anti-CCP1 and anti-CCP2. Conclusion. Anti-CCP test was more sensitive and specific than traditional IgM-RF. However, anti-CCP2 was not significantly better than anti-CCP1 in the diagnosis of RA.

The Taiwan Rheumatology Association Consensus Recommendations for hepatitis B virus screening contributes to lower mortality from hepatitis B reactivation in rheumatic patients: a local medical center study

目的：評估自「2012年風濕病醫學會免疫風濕病患接受生物製劑治療B型肝炎篩檢與防治共識建議」發布後，本院風濕疾病患者使用biological originator disease-modifying antirheumatic drugs（boDMARDs）或targeted synthetic disease-modifying antirheumatic drugs（tsDMARDs）之B型肝炎篩檢率及B型肝炎再活化（reactivation）事件是否有改善。方法：統計自2006年1月起至2015年12月止，本院有215位類風溼性關節炎、僵直性脊椎炎或乾癬性關節炎患者使用boDMARDs，包括了etanercept, adalimumab, golimumab, tocilizumab, rituximab,abatacept或是使用tsDMARD tofacitinib，計算其B型肝炎篩檢率以及B型肝炎再活化之事件發生率。結果：經過篩選，共207位病患納入此研究。類風濕性關節炎患者之B型肝炎表面抗原篩檢率由原本的21.5%提升至77.8%；然而僵直性脊椎炎及乾癬性關節炎患者之B型肝炎表面抗原篩檢率並無顯著差異。B型肝炎再活化之事件/病患-年發生率，在經過遵行防治共識建議後由0.125降至0.056，其中，死亡率由25%降至0%。結論：由於台灣是B型肝炎高盛行率之國家，因此B型肝炎防治是非常重要的衛生議題。經由此次研究統計可觀察到在經由遵行「2012年風濕病醫學會免疫風濕病患接受生物製劑治療B型肝炎篩檢與防治共識建議」之後，病患的B型肝炎篩檢率提高且B型肝炎再活化之事件發生率及死亡率降低。建議應謹遵其行。

Diagnostic Validity of Computed Tomography for HLA-B27 Negative Ankylosing Spondylitis: A Retrospective Study of 209 Patients

Objective: Radiographic sacroiliitis is considered the hallmark of ankylosing spondylitis (AS). However, large interobserver variations make plain radiographic diagnosis of sacroiliitis notoriously difficult. The heterogeneity of HLA-B27 negative AS makes its diagnosis even more challenging. Several reports have shown that sacroiliitis tends to be underestimated using radiography, and that computed tomography (CT) facilitates AS diagnosis in patients with suspected spondyloarthritis. However, no studies have stressed the clinical utility of CT, particularly in the diagnosis of HLA-B27(-) AS. Methods: We retrospectively evaluated 209 HLA-B27(-) patients with chronic lower back pain and suspected AS. Radiography and CT reports were examined and outcomes were compared. Results: Among 408 sacroiliac (SI) joints examined using both radiography and CT, there was agreement between the two methods in the sacroiliitis grading of 82 (20.1%) SI joints. However, sacroiliitis grade using CT was higher in 276 (67.6%) SI joints and lower in 50 (12.3%) SI joints. CT evaluation of SI joints showed that 78.9% of patients met the radiographic sacroiliitis criteria of the modified New York criteria, while only 26% of patients satisfied the criteria for plain radiography. Surprisingly, 117 patients (57.3%), who did not meet the modified New York AS diagnosis criteria for plain radiography met the criteria for CT. Conclusion: CT was sensitive and useful in providing evidence for the diagnosis of AS. We suggest that HLA-B27(-) patients with equivocal plain radiography results and chronic inflammatory lower back pain be examined using CT.

A Retrospective Investigation of Ultrasound Findings in Patients with Shoulder Pain from One Center in Northern Taiwan

Objective: Research has shown that 15-30% of adults experience shoulder pain at some point during the course of their lives. The sensitivity and specificity of musculoskeletal ultrasound (MSUS) have been validated, showing that this tool can complement surgical findings and magnetic resonance imaging. We report ultrasound findings of patients with shoulder pain in rheumatological daily practice. Methods: The subject population for this retrospective study included 240 patients complaining of shoulder pain at the MSUS department of our rheumatology service between January 2010 and December 2012. The ultrasound examination included views of the rotator cuff, the long head of the biceps tendon, the subacromial-subdeltoid bursa, the acromioclavicular joint, and the glenohumeral joint. Results: Of the 240 patients, 140 were women and 100 were men, with ages ranging from 17 to 89 years and a mean age of 54.31 ± 14.64 years. Alterations of shoulder structures were detected in the supraspinatus tendon (76.2%), biceps tendon (62.4%), subscapularis tendon (22.9%), glenohumeral joint (20.4%), acromioclavicular joint (15.3%), subacromial-subdeltoid bursa (13.3%), and infraspinatous tendon (9.2%). Impingement (14.1%) and calcifications (8.2%) were also detected. Eight patients (3.3%) exhibited no sonographic evidence of any alteration. The sensitivity of the technique was confirmed by the finding of alterations in 96.7% of the cases. Conclusion: Although physical examination allows for a diagnostic approach in the treatment of shoulder pain, the technique is typically not accurate enough to ensure that the correct diagnosis is made. MSUS offered the precision necessary to detect the underlying pathology in 97% of the cases.

Predictive Value of erythrocyte-bound C4d to erythrocyte-complement Receptor Type 1 Ratio in Lupus Disease Activity

Objective: Erythrocyte-bound C4d (E-C4d) and erythrocyte-complement receptor type 1 (E-CR1) are both novel biomarkers to diagnose systemic lupus erythematosus (SLE) and to monitor disease activity. This study aimed at determining the ratio of E-C4d to E-CR1 (E-C4d/E-CR1) using mouse monoclonal antibody CR1-2B11 and correlating the clinical association of this ratio with disease activity of SLE. Methods: This study included 6 SLE patients, and their blood samples were collected before and after immunosuppressive therapy. E-C4d and E-CR1 levels were measured using indirect immunofluorescence and flow cytometry on the same day as the blood drawing, and the E-C4d/E-CR1 ratios were calculated from the values obtained. Results: The mean of the E-C4d/E-CR1 ratio was significantly decreased in SLE patients after immunosuppressive therapy (12.93±1.9 vs. 3.52±0.9, p＜0.05). Three of the 6 SLE patients showed decreased ratios when their active disease stabilized after adequate treatment respectively (19.23 to 1.01, 5.47 to 1.25, and 13.16 to 2.40). Conclusion: The reciprocal change in E-C4d and E-CR1 levels is important in SLE patients. The E-C4d/E-CR1 ratio assessed with CR1-2B11 could be a good biomarker to predict disease activity and may be helpful in formulating a therapeutic strategy in SLE.