HBV reactivation in HBsAg-/HBcAb+ rheumatoid arthritis patients receiving biologic/targeted synthetic DMARDs.

BACKGROUND: Rheumatoid arthritis (RA) patients seropositive for hepatitis B core antibody (HBcAb) and negative for hepatitis B surface antigen (HBsAg) are at risk of hepatitis B virus (HBV) reactivation when treated with biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs). The study aims to investigate the risk in this population. METHODS: From January 2004 through December 2020, 1068 RA patients undergoing b/tsDMARDs therapy and 416 patients with HBsAg-/HBcAb+ were enrolled. Factors associated with HBV reactivation were analysed. RESULTS: During 2845 person-years of follow-up, 27 of 416 (6.5%,9.5 per 1000 person-years) patients developed HBV reactivation, with a cumulative rate of HBV reactivation of 3.5% at 5 years, 6.1% at 10 years and 24.2% at 17 years. The median interval from beginning b/tsDMARDs to HBV reactivation was 85 months (range: 9-186 months). The risk of HBV reactivation varied by type of b/tsDMARD, with rituximab having the highest risk (incidence rate: 48.3 per 1000 person-years), followed by abatacept (incidence rate: 24.0 per 1000 person-years). In multivariate analysis, rituximab (adjusted hazard ratio [aHR]: 15.77, 95% confidence interval [CI]: 4.12-60.32, p = .001), abatacept (aHR: 9.30, 1.83-47.19, p = .007), adalimumab (aHR: 3.86, 1.05-14.26, p = .04) and negative baseline HBV surface antibody (anti-HBs, <10 mIU/mL) (aHR: 3.89, 1.70-8.92, p < .001) were independent risk factors for HBV reactivation. CONCLUSION: HBsAg-/HBcAb+ RA patients are susceptible to HBV reactivation during b/tsDMARD therapy. Those with negative baseline anti-HBs and those on certain b/tsDMARDs, such as rituximab, abatacept and adalimumab, have high reactivation risks. Risk stratification and management should be based on the patient's baseline anti-HBs titre and type of therapy.

Increased risk of hospital admissions in patients with active systemic lupus erythematosus (SLE) classified according to two different SLE disease activity indices: a prospective cohort study.

OBJECTIVES: The aim of this prospective cohort study was to investigate the risk of hospital admissions within one year in patients with active systemic lupus erythematosus (SLE), classified according to the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) or the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). METHODS: This study was conducted in adult patients with SLE recruited from the rheumatology outpatient department in a regional hospital in southern Taiwan. SLE disease activity was measured with SLE-DAS and SLEDAI-2K. The computerised patient record database was accessed to identify patients' hospital admissions. Cox regression analyses were used to estimate the hazard ratio (HR) for all-cause and SLE-related hospital admission in SLE patients classified by SLE-DAS and SLEDAI-2K. RESULTS: A total of 326 adult patients with SLE completed this study. All-cause and SLE-related hospital admissions within one year occurred in 17.5% and 12.6% of the patients, respectively. Results of the Cox regression analysis indicated that SLE patients with moderate/severe disease activity classified by the SLE-DAS (HR=2.43, p=0.005) but not moderate/severe disease activity classified by the SLEDAI-2K (HR=1.84, p=0.057) was significantly associated with the risk of SLE-related admissions. However, only moderate/severe disease activity classified by the SLE-DAS was significantly associated with the risk of all-cause admissions (HR=1.94, p=0.016). When steroid dosage was considered, only the steroid dosage was significantly associated all-cause and SLE-related admissions. CONCLUSIONS: In this study, SLE disease activity classified by SLE-DAS was significantly associated with an increased risk for both all-cause and SLE-related hospital admissions. Rheumatologists should be vigilant for increased risk of hospital admissions in patients with moderate/high SLE disease activity as classified by SLE-DAS.

Increased Expression of Long Noncoding RNA LOC100506314 in T cells from Patients with Nonsegmental Vitiligo and Its Contribution to Vitiligo Pathogenesis.

This study aimed to identify the abnormal expression of long noncoding RNAs (lncRNAs) in T cells from patients with vitiligo and to investigate their functional roles in the immune system. Using microarray analysis, the expression levels of RNA transcripts in T cells from patients with vitiligo and controls were compared. We identified several genes and validated their expression levels in T cells from 41 vitiligo patients and 41 controls. The biological functions of the lncRNAs were studied in a transfection study using an RNA pull-down assay, followed by proteomic analysis and western blotting. The expression levels of 134 genes were significantly increased, and those of 142 genes were significantly decreased in T cells from vitiligo patients. After validation, six genes had increased expression, and three genes had decreased expression in T cells from patients with vitiligo. T-cell expression of LOC100506314 was increased in vitiligo, especially CD4+, but not CD8+ T cells. The expression levels of LOC100506314 in CD4+ T cells was positively and significantly associated with the severity of vitiligo. LOC100506314 was bound to the signal transducer and activator of transcription 3 (STAT3) and macrophage migration inhibitory factor (MIF). Enhanced expression of LOC100506314 inhibited the phosphorylation of STAT3, protein kinase B (AKT), and extracellular signal-regulated protein kinases (ERK), as well as the levels of nuclear protein of p65 and the expression of IL-6 and IL-17 in Jurkat cells and T cells from patients with vitiligo. In conclusion, this study showed that the expression of LOC100506314 was elevated in CD4+ T cells from patients with vitiligo and associated the severity of vitiligo. LOC100506314 interacted with STAT3 and MIF and inhibited IL-6 and IL-17 expression by suppressing the STAT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), AKT, and ERK pathways. Enhanced expression of LOC100506314 in T cells may be a potential treatment strategy for vitiligo.

Relationship between Chinese Herbal Medicine Use and Risk of Sjögren's Syndrome in Patients with Rheumatoid Arthritis: A Retrospective, Population-Based, Nested Case-Control Study.

Background and Objectives: Sjögren's Syndrome (SS) is a common extra-articular feature among subjects with rheumatoid arthritis (RA). While Chinese herbal medicine (CHM) has been used to treat symptoms of RA for many years, few studies have examined its efficacy in guarding against the SS onset. This study aimed to compare risk of SS for RA patients with and without use of CHM. Materials and Methods: Data obtained for this nested case-control study were retrieved from Taiwanese nationwide insurance database from 2000-2013. Cases with SS claims were defined and matched to two randomly selected controls without SS from the recruited RA cohorts. Risk of SS in relation to CHM use was estimated by fitting multiple conditional logistic regression. Results: Patients aged between 20 and 80 years were included and 916 patients with incident SS were matched to 1832 non-SS controls by age, sex and index year. Among them, 28.1% and 48.4% cases ever received CHM therapy, respectively. After adjusting for baseline characteristics, CHM use was found to be related to a lower risk of SS among them (adjusted odds ratio = 0.40, 95% confidence interval: 0.34-0.47). A dose-dependent, reverse association, was further detected between the cumulative duration of CHM use and SS risk. Those receiving CHM therapy for more than 730 days showed a significantly reduced risk of SS by 83%. Conclusions: Findings of this study indicated that the add-on CHM formula, as part of RA care, may be a beneficial treatment for prevention against the incident SS.

HLA-B*27 Heavy Chain Homo-Oligomers Promote the Cytotoxicity of NK Cells via Activation of PI3K/AKT Signaling.

Background and Objectives: Ankylosing spondylitis (AS) is a chronic inflammatory disease and is highly linked with the expression of the human leukocytic antigen-B*27 (HLA-B*27) genotype. HLA-B*27 heavy chain (B*27-HC) has an innate characteristic to slowly fold, resulting in the accumulation of the misfolded B*27-HC and the formation of homo-oligomeric B*27-HC molecules. The homo-oligomeric B*27-HC can act as a ligand of KIR3DL2. Interaction of the homo-oligomeric B*27-HC molecules with KIR3DL2 will trigger the survival and activation of KIR3DL2-positive NK cells. However, the effects of homo-oligomeric B*27-HC molecules associated with KIR3DL2 on the cytotoxic activity of NK cells and their cytokine expressions remain unknown. Materials and Methods: HLA-B*-2704-HC was overexpressed in the HMy2.C1R (C1R) cell line. Western blotting and quantitative RT-PCR were used to analyze the protein expression and cytokine expression, respectively, when C1R-B*-2704 cells that overexpress B*2704-HC were co-cultured with NK-92MI cells. Flow cytometry was used to analyze the cytotoxicity mediated by NK-92MI cells. Results: Our results revealed that NK-92MI cells up-regulated the expression of perforin and enhanced the cytotoxic activity via augmentation of PI3K/AKT signaling after co-culturing with C1R-B*2704 cells. Suppression of the dimerized B*27-HC formation or treatment with an inhibitor of PI3K, LY294002, or with an anti-B*27-HC monoclonal antibody can reduce the perforin expression of NK-92MI after co-culturing with C1R-B*-2704. Co-culturing with C1R-B*-2704 cells suppressed the TNF-α and IL6 expressions of NK-92MI cells. Conclusion: Stimulation of NK cell-mediated cytotoxicity by homo-oligomeric B*27-HC molecules may contribute to the pathogenesis of AS.

Risk of Hepatitis B Virus Reactivation in Rheumatoid Arthritis Patients Undergoing Tocilizumab-Containing Treatment.

BACKGROUND AND AIM: To investigate the risk of hepatitis B virus reactivation in patients undergoing long-term tocilizumab therapy for rheumatoid arthritis. METHOD: From January 2011 through August 2019, a total of 97 patients were enrolled in this retrospective study. Clinical data, comedications, and the occurrence of HBV reactivation were recorded. RESULTS: Seven patients were HBsAg+ (7.2%), 64 were HBsAg-/HBcAb+ (65.9%), and 26 were HBsAg-/HBcAb- (26.8%). The median disease follow-up time was 9 years. TCZ was administered for a median of 29 months. Four patients (4.1%) experienced HBV reactivation after tocilizumab therapy. Of the 7 HBsAg+ patients, 4 received antiviral prophylaxis and had no HBV reactivation; the remaining 3 patients did not receive antiviral prophylaxis, and all 3 (100%) experienced HBV reactivation and hepatitis flare-up. Hyperbilirubinemia occurred in 2 of these 3 patients, with mild prothrombin time prolongation in one. After salvage entecavir treatment, all patients had a favorable outcome. Of the 64 HBsAg-/HBcAb+ patients, only one became positive for serum HBV DNA (2.5 × 107 IU/mL) after 18 months of tocilizumab treatment (1.6%; 1/64). This patient was immediately treated with entecavir, which prevented hepatitis flare-up. CONCLUSIONS: Tocilizumab is widely used in treating rheumatoid arthritis and has the potential to reduce the mortality rate among severe COVID-19 patients. However, HBV reactivation needs to be considered. HBsAg+ patients have a high risk of HBV reactivation, which could be prevented by antiviral prophylaxis. Although the risk of reactivation is low in HBsAg-/HBcAb+ patients, strict monitoring is necessary.

Increased Serum Levels of Brain-Derived Neurotrophic Factor Contribute to Inflammatory Responses in Patients with Rheumatoid Arthritis.

The aim of this study is to investigate the role of brain-derived neurotrophic factor (BDNF) in the inflammatory responses in patients with rheumatoid arthritis (RA). Serum levels of BDNF and the precursor form of BDNF (proBDNF) from 625 RA patients and 40 controls were analyzed using enzyme-linked immunosorbent assay. Effects of BDNF on the mitogen-activated protein kinase pathway were analyzed by Western blotting. Microarray analysis was conducted to search BDNF regulated gene expression in Jurkat cells, and the differentially expressed genes were validated using T cells from patients with RA and controls. Serum BDNF levels were significantly elevated in patients with RA compared with the controls. Low serum BDNF levels were found in RA patients with anxiety or receiving biologics treatment. BDNF (20 ng/mL) enhanced the phosphorylation of ERK, JNK, and c-Jun, but suppressed the phosphorylation of p38, whereas BDNF (200 ng/mL) enhanced the phosphorylation of ERK and p38. After validation, the expression of CAMK2A, MASP2, GNG13, and MUC5AC, regulated by BDNF and one of its receptors, NGFR, was increased in RA T cells. BDNF increased the IL-2, IL-17, and IFN-γ expression in Jurkat cells and IL-2 and IFN-γ secretion in activated peripheral blood mononuclear cells.

Identification of phostensin in association with Eps 15 homology domain-containing protein 1 (EHD1) and EHD4.

Phostensin (PTS) encoded by KIAA1949 is a protein phosphatase 1 (PP1)-binding protein. In order to explore the cellular functions of PTS, we have searched PTS-binding proteins by using co-immunoprecipitation in combination with shotgun proteomics. Here, we report two novel PTS-binding proteins, Eps 15 homology domain-containing protein 1 (EHD1) and EHD4. PTS associated with EHD proteins was also observed in GST pull-down assays. Immunofluorescence microscopy demonstrated that the complex was co-localized at the endocytic vesicles. EHD proteins have been known to play a critical role in regulation of endocytic transport. Overexpression of PTS-ß can attenuate the endocytic trafficking of transferrin.

The effectiveness of nurse-led case management for patients with rheumatoid arthritis in Taiwan.

BACKGROUND: Case management is a patient-centred approach which has shown efficacy in managing patients with chronic and life-threatening disease. Presently, the effect of case management delivered by nurses for rheumatoid arthritis (RA) patients remains unclear, especially for those subjects who reside in Asia. This study aimed to examine the effectiveness of nurse-led case management (NLCM) among RA patients in Taiwan. METHODS: A quasi-experimental research design was utilised to recruit RA patients from a hospital in Taiwan. All patients who were diagnosed as having RA from January 2017 to June 2018 were free to opt to participate in the intervention. The experiment group (n = 50) received six sessions of NLCM over six months, while the control group (n = 46) received only standard care during the same time period. Effectiveness data were collected through the review of medical records and a structured questionnaire that included the Taiwanese Depression Questionnaire (TDQ), the arthritis self-efficacy scale and a disease activity score by 28 joints (DAS28) at three time points (T1: before NLCM; T2: three days after NLCM completion; and T3: six months after NLCM completion). The effects of NLCM were determined using a generalised estimating equations model. RESULTS: After adjusting for several potential confounders, we found that the NLCM implementation decreased the levels of DAS28 (T1 = -0.78; T2 = -0.85; all at P = .01) and TDQ (T1 = -3.86; T2 = -10.57; all at P < .05) and enhanced ASES level for RA patients (T1 = 132.03; T2 = 484.69; all at P < .05). CONCLUSIONS: This study adopted a non-randomised, unblinded and uncontrolled intervention, and the findings supported the positive effects of NLCM following the use of a robust statistical method. The findings may serve as a reference for instituting more appropriate interventions for RA patients.

Fiber Optic Particle Plasmon Resonance Biosensor for Label-Free Detection of Nucleic Acids and Its Application to HLA-B27 mRNA Detection in Patients with Ankylosing Spondylitis.

We developed a label-free, real-time, and highly sensitive nucleic acid biosensor based on fiber optic particle plasmon resonance (FOPPR). The biosensor employs a single-strand deoxyoligonucleotides (ssDNA) probe, conjugated to immobilized gold nanoparticles on the core surface of an optical fiber. We explore the steric effects on hybridization affinity and limit of detection (LOD), by using different ssDNA probe designs and surface chemistries, including diluent molecules of different lengths in mixed self-assembled monolayers, ssDNA probes of different oligonucleotide lengths, ssDNA probes in different orientations to accommodate target oligonucleotides with a hybridization region located unevenly in the strand. Based on the optimized ssDNA probe design and surface chemistry, we achieved LOD at sub-nM level, which makes detection of target oligonucleotides as low as 1 fmol possible in the 10-mL sensor chip. Additionally, the FOPPR biosensor shows a good correlation in determining HLA-B27 mRNA, in extracted blood samples from patients with ankylosing spondylitis (AS), with the clinically accepted real-time reverse transcription-polymerase chain reaction (RT-PCR) method. The results from this fundamental study should guide the design of ssDNA probe for anti-sense sensing. Further results through application to HLA-B27 mRNA detection illustrate the feasibility in detecting various nucleic acids of chemical and biological relevance.

Factors associated with sexual dysfunction in Taiwanese females with rheumatoid arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) may experience sexual dysfunction because of symptoms or adverse effects from treatments. Data on female sexual dysfunction (FSD) in Asian females with RA issue are limited. This study investigated the prevalence and factors associated with FSD in Taiwanese patients with RA. METHODS: This cross-sectional study used a purposive sampling method to recruit 195 females with RA from a single hospital in southern Taiwan. Demographic and clinical characteristics were obtained by review of medical records and a structured questionnaire. The Chinese version of the Female Sexual Function Index and the Taiwanese Depression Questionnaire were also administered. Multiple logistic regression analysis was used to identify factors associated with FSD. RESULTS: The crude and age-standardized prevalence of FSD were 66.8% and 48.2%, respectively. Patients who were older, with a comorbid condition, with more depressive symptoms, and with greater disease activity had a significantly higher risk of FSD. CONCLUSION: Our findings indicate that FSD is more common in Taiwanese individuals with RA who have certain specific demographic and clinical characteristics. These findings may help to identify and facilitate the provision of appropriate interventions to ensure better sexual health in female patients with RA.

Targeted Delivery of the HLA-B∗27-Binding Peptide into the Endoplasmic Reticulum Suppresses the IL-23/IL-17 Axis of Immune Cells in Spondylarthritis.

Ankylosing spondylitis (AS) is highly associated with the expression of human leukocyte antigen-B27 (HLA-B∗27). HLA-B∗27 heavy chain (B27-HC) has an intrinsic propensity to fold slowly, leading to the accumulation of the misfolded B27-HC in the endoplasmic reticulum (ER) and formation of the HLA-B∗27 HC homodimer, (B27-HC)2, by a disulfide linkage at Cys-67. (B27-HC)2 displayed on the cell surface can act as a ligand of the killer-cell Ig-like receptor (KIR3DL2). (B27-HC)2 binds to KIR3DL2 of NK and Th17 cells and activates both cells, resulting in the activation of the IL-23/IL-17 axis to launch the inflammatory reaction in AS patients. However, activation of the IL-23/IL-17 axis originally derived from the HLA-B∗27 misfolding in the ER needs to be characterized. In this study, we delivered two HLA-B∗27-binding peptides, KRGILTLKY and SRYWAIRTR, into the ER by using a tat-derived peptide (GRKKRRQRRR)-His6-ubiquitin (THU) vehicle. Both peptides are derived from the human actin and nucleoprotein of influenza virus, respectively. Our results demonstrated that targeted delivery of both HLA-B∗27-binding peptides into the ER can promote the HLA-B∗27 folding, decrease the levels of (B27-HC)2, and suppress the activation of the IL-23/IL-17 axis in response to lipopolysaccharide. Our findings can provide a new therapeutic strategy in AS.

Risk of Sjögren's syndrome in Taiwanese female adults with irregular menstrual cycles: a population-based case-control study.

Primary Sjögren's syndrome (pSS) is a progressive systemic autoimmune disorder with a strong female predominance. Hormonal influences are thought to play a role in the development of pSS. However, no studies have specifically evaluated the association between irregular menstrual cycles and pSS. Therefore, using a health claims database, this study investigated the risk of pSS in women with irregular menstrual cycles. We conducted a case-control study using the Taiwan's National Health Insurance Research Database. A total of 360 patients diagnosed with pSS (International Classification of Diseases, ninth revision, clinical modification, ICD-9-CM code 710.2) between 2001 and 2012 were identified. Controls were frequency-matched at a rate of 5:1 to the cases by five-year age interval and index year. Both cases and controls were retrospectively traced back until 2001 for the diagnosis of irregular menstrual cycles (ICD-9-CM code 626.4). The risk of pSS was assessed using multivariate logistic regression analyses. Irregular menstrual cycles were significantly associated with pSS [adjusted odds ratio, (AOR) = 1.38, p = 0.027], after adjusted for insured amount, urbanization level, and thyroid disorder. In addition, when the data were stratified by three age categories, only the patients in the age category of 45-55 years showed significant association between irregular menstrual cycles and pSS (AOR = 1.74, p = 0.005). In this nationwide, population-based case-control study, we found a significant increased risk of pSS in female patients with irregular menstrual cycles, particularly those in their mid-forties to mid-fifties.

Increased Serum Levels of Anti-Carbamylated 78-kDa Glucose-Regulated Protein Antibody in Patients with Rheumatoid Arthritis.

The objective of this study was to investigate the presence and titer of anti-carbamylated 78-kDa glucose-regulated protein (anti-CarGRP78) antibody in serum from controls, and patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS). Thirty-three RA patients, 20 SLE patients, 20 pSS patients, and 20 controls were enrolled from our outpatient clinic. GRP78 was cloned and carbamylated. Serum titers of anti- cyclic citrullinated peptides (anti-CCP), anti-GRP78, and anti-CarGRP78 were measured with an enzyme-linked immunosorbent assay. No differences in serum titers of anti-GRP78 antibody in patients with RA, SLE, or pSS compared with the controls were observed. Serum levels of anti-carGRP78 antibody in patients with RA, but not SLE or pSS, were significantly higher compared with the controls (OD405 0.15 ± 0.08 versus 0.11 ± 0.03, p = 0.033). There was a positive correlation between the serum levels of anti-GRP78 antibody, but not anti-CarGRP78 antibody, with the levels of anti-CCP antibody in patients with RA. Both anti-GRP78 and anti-carGRP78 antibodies failed to correlate with C-reactive protein levels in patients with RA. In conclusion, we demonstrated the presence of anti-CarGRP78 antibody in patients with RA. In addition, the serum titer of anti-CarGRP78 antibody was significantly elevated in patients with RA compared with the controls. Anti-CarGRP78 antibody could also be detected in patients with SLE or pSS.

Aberrant T cell expression of Ca2+ influx-regulated miRNAs in patients with systemic lupus erythematosus promotes lupus pathogenesis.

OBJECTIVE: The aim of this study was to investigate the pathogenic role of calcium (Ca(2+)) influx-regulated microRNAs (miRNAs) in T cells from patients with SLE. METHODS: Expression profiles of 270 human miRNAs in Jurkat cells co-cultured with or without ionomycin were analysed by real-time PCR. Differential expression of miRNAs in T cell samples from 28 patients with SLE (SLE T cells) and 20 healthy controls were investigated using western blot analysis of proteins expressed by respective miRNA target transcripts. Transfection studies were conducted to investigate miRNA-specific biological functions. RESULTS: Initial analysis revealed differential expression of nine miRNAs in Jurkat cells after co-culture with ionomycin. Of these, miR-524-5p and miR-449b were overexpressed in SLE T cells. Levels of expressed miR-524-5p showed a significant direct correlation with the SLEDAI. Transfection of Jurkat cells with miR-524-5p mimic suppressed Jagged-1 and Hes-1 protein expression. Likewise, expression of both Jagged-1 and Hes-1 proteins were diminished in SLE T cells. Upon activation of Jurkat cells transfected with miR-524-5p mimic, production of IFN-γ increased but the apoptotic rate was unaffected. CONCLUSION: In SLE T cells, miR-524-5p and miR-449b (both regulated by Ca(2+) influx) were overexpressed. Moreover, increased miR-524-5p expression, as shown by patients with SLE, directly paralleled disease activity (SLEDAI). Transfection of miR-524-5p also enhanced IFN-γ production in activated Jurkat cells.

Association of rheumatoid arthritis with allergic diseases: A nationwide population-based cohort study.

BACKGROUND: Low-grade inflammation conditions, e.g., type 2 diabetes, have been shown to be associated with an increased risk of rheumatoid arthritis (RA). However, the association between other chronic inflammatory conditions, e.g., asthma, allergic rhinitis, and atopic dermatitis, is still unclear. OBJECTIVE: To investigate the risk of RA in patients with allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis, by using a nationwide health claims database. METHODS: The Taiwan National Health Insurance Research Database was used to assemble a cohort of 170,570 patients ages 20 years old and older diagnosed with allergic diseases, including asthma, allergic rhinitis, or atopic dermatitis. A comparison cohort of 170,238 patients was constructed from the same data base, with frequency matching for sex, 10-year age group, and year of insurance enrollment. Cox proportional hazards regression analyses were conducted to assess the association between the allergic diseases and incident RA. RESULTS: Asthma (adjusted hazard ratio [AHR] 1.67, [95% confidence interval {CI}], 1.32-2.62) and allergic rhinitis (AHR 1.62 [95% CI, 1.33-1.98]) were significantly associated with the incident RA. These associations remained significant even after excluding patients who had concurrent diagnoses of asthma and allergic rhinitis. Patients with more than one allergic disease had an increased risk of developing RA (AHR 1.98 [95% CI, 1.50-2.62]). Subgroup analysis further indicated that middle-aged and elderly female patients with more than one allergic disease exhibited a high risk of developing RA. CONCLUSION: Significant associations between common allergic diseases and incident RA was found in this population-based cohort study. Our findings provided support to the hypothesis that allergic diseases and RA might share a similar underlying etiologic pathway related to chronic inflammatory responses.

Clinimetric properties of the Chinese version of the early inflammatory arthritis detection tool.

BACKGROUND: Timely rheumatologic referral and management are crucial for patients with potential inflammatory arthritis. To meet this need, tools such as the early inflammatory arthritis (EIA) detection tool was developed and has been evaluated in Western populations. The aims of this study were to translate the English version of the EIA detection tool to Chinese and to determine its clinimetric properties in Taiwanese patients. METHODS: Twenty controls and 111 patients with established diagnosis of osteoarthritis, rheumatoid arthritis, systemic autoimmune diseases, psoriatic arthritis, and ankylosing spondylitis were recruited from a regional hospital in south Taiwan. Multivariate logistic regression analysis was used to evaluate the independent and significant variables associated with diagnosis by rheumatologists. A prediction model was also developed for differentiating between patients with inflammatory arthritis and those with non-inflammatory arthritis musculoskeletal conditions. RESULTS: The Chinese version of the EIA detection tool showed acceptable internal consistency (KR-20 coefficient 0.78) and test-retest reliability (κ statistic ranged from 0.43 to 0.94). A prediction model consisting of three EIA detection tool items (joint pain, swelling in hands or wrists, and ever been told to have rheumatoid arthritis) and sex was able to differentiate inflammatory arthritis and non-inflammatory arthritis musculoskeletal conditions with a sensitivity of 0.84, a specificity of 0.86, a positive predictive value of 0.92, and a negative predictive value of 0.76. CONCLUSIONS: The Chinese version of the EIA detection tool showed good clinimetric properties in this study population and it can be used to differentiate Taiwanese patients with inflammatory arthritis and non-inflammatory arthritis musculoskeletal conditions.

BK virus as a potential oncovirus for bladder cancer in a renal transplant patient.

Renal transplant patients have high risk for bladder cancer. The reactivation of BK virus is common in renal transplant patients especially in the urinary tract. There was some evidence suggesting that the reactivation of BK virus (BKV) in renal transplant patients may associate with the development of bladder cancer. Here we demonstrated that a patient that had persistent elevated BKV viruria (urine BKV DNA concentration more than 10(11) copies/ml) after renal transplantation. Then, bladder cancer was found in 13 months after kidney transplantation. The urine BKV DNA concentration was detected by real-time PCR and the BKV DNA in the bladder tumor was detected by PCR. BKV DNA was found in the marginal and central part of the bladder tumor. After removal of the bladder cancer, the urine BKV viral load in this patients dropped dramatically to <10(2) copies/ml. However, the urine viral load had increased modestly to 10(6) copies/ml in 3 months after surgery. Since there is a close correlation between the urine BK viral load and the presence of bladder cancer, we suggested that there might be a causal relationship between the reactivation of BKV and the development of bladder cancer in renal transplant patient.

Sulfasalazine Treatment Suppresses the Formation of HLA-B27 Heavy Chain Homodimer in Patients with Ankylosing Spondylitis.

Human leukocytic antigen-B27 heavy chain (HLA-B27 HC) has the tendency to fold slowly, in turn gradually forming a homodimer, (B27-HC)2 via a disulfide linkage to activate killer cells and T-helper 17 cells and inducing endoplasmic reticulum (ER) stress to trigger the IL-23/IL-17 axis for pro-inflammatory reactions. All these consequences lead to the pathogenesis of ankylosing spondylitis (AS). Sulfasalazine (SSA) is a common medication used for treatment of patients with AS. However, the effects of SSA treatment on (B27-HC)2 formation and on suppression of IL-23/IL-17 axis of AS patients remain to be determined. In the current study, we examine the (B27-HC)2 of peripheral blood mononuclear cells (PBMC), the mean grade of sarcoiliitis and lumbar spine Bath Ankylosing Spondylitis Radiology Index (BASRI) scores of 23 AS patients. The results indicated that AS patients without (B27-HC)2 on PBMC showed the lower levels of mean grade of sarcoiliitis and the lumbar spine BASRI scores. In addition, after treatment with SSA for four months, the levels of (B27-HC)2 on PBMCs were significantly reduced. Cytokines mRNA levels, including TNFα, IL-17A, IL-17F and IFNγ, were also significantly down-regulated in PBMCs. However, SSA treatment did not affect the levels of IL-23 and IL-23R mRNAs.

Characterization of the recognition specificity of BH2, a monoclonal antibody prepared against the HLA-B27 heavy chain.

BH2, a monoclonal antibody prepared against the denatured human leukocytic antigen-B27 heavy chain (HLA-B27 HC), can immunoprecipitate the misfolded HLA-B27 HC complexed with Bip in the endoplasmic reticulum and recognize the homodimerized HLA-B27 HC that is often observed on the cell membrane of patients suffered from ankylosing spondylitis (AS). However, the recognition specificity of BH2 toward the other molecules of HLA-B type and toward the different types of HLA molecules remained uncharacterized. In this study, we carried out the HLA-typing by using the Luminex Technology to characterize the recognition specificity of BH2 and analyzed the binding domain of HLA-B27 HC by BH2. Our results indicated that BH2 preferably binds to molecules of HLA-B and -C rather than HLA-A and the binding site is located within the α2 domain of HLA-B27 HC.