Rheumatoid Arthritis: Zhang B

Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C, Bombardieri S, Choi H, Combe B, Dougados M, Emery P, Gomez-Reino J, Keystone E, Koch G, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Michaud K, O'Dell J, Paulus H, Pincus T, Richards P, Simon L, Siegel J, Smolen JS, Sokka T, Strand V, Tugwell P, van der Heijde D, van Riel P, Vlad S, van Vollenhoven R, Ward M, Weinblatt M, Wells G, White B, Wolfe F, Zhang B, Zink A, Felson D, Anonymous00358, Anonymous00359. · Medical University of Vienna, Vienna, Austria. · Arthritis Rheum. · Pubmed #18821648 No free full text.

Abstract: OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardized operating procedures, which use a three-step approach: 1) expert-based definition of relevant research questions (November 2006); 2) systematic literature search (November 2006 to May 2007); and 3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature, the expert panel recommended that each trial should report the following items: 1) disease activity response and disease activity states; 2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; 3) baseline disease activity levels (in general); 4) the percentage of patients achieving a low disease activity state and remission; 5) time to onset of the primary outcome; 6) sustainability of the primary outcome; 7) fatigue. CONCLUSION: These recommendations endorsed by EULAR and ACR will help harmonize the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

Zhang B, Wang CH, Wang YH, Fan CM, Zhu P. · Department of Clinical Immunology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. · Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. · Pubmed #19426598 No free full text.

Abstract: AIM: To ascertain the effect of CyPA and IL-8 in chemotaxis of neutrophil and the level of IL-8 from the CyPA effecting of peripheral blood from RA patients. METHODS: 12 RA patients matched 4 healthy people were studied. Chemotaxis of IL-8 was measured by Boyden chamber on neutrophil of RA patients and that of 4 normal healthy people controls were studied; the level of IL-8 on neutrophil of RA patients peripheral blood after the effecting of CyPA was assessed by ELISA. Correlations between CyPA and IL-8 were observed in RA. RESULTS: The chemotaxis of neutrophil which IL-8 mixed with CyPA antibody was lower than IL-8(P<0.05); The secretion of RA peripheral blood in IL-8 was higher than normal people, as well as the secretion of RA peripheral blood in IL-8 after effecting of CyPA was higher than before (P<0.05), but the level of IL-8 after blocking CyPA was not changed. CONCLUSION: CyPA could affect the chemotaxis of IL-8 in the neutrophil of RA patients' peripheral blood. The secretion of IL-8 is accelerated by CyPA on neutrophil of RA patients'peripheral blood.

Allaire S, Wolfe F, Niu J, LaValley MP, Zhang B, Reisine S. · Boston University School of Medicine, Boston, Massachusetts 02118, USA. · Arthritis Rheum. · Pubmed #19248135 No free full text.

Abstract: OBJECTIVE: To explore, using recent data, whether and how risk factors for rheumatoid arthritis (RA) work disability may differ from previous studies. METHODS: Subjects were 953 individuals with RA from a US cohort who provided data semiannually over 18 months (years 2002-2005). A nested case-control design was used with matching on time of baseline data collection. All subjects were employed at baseline; cases were consistently not employed at followup, whereas controls remained employed. Hierarchical conditional logistic regression assessed the roles of demographic, RA disease, general health, and work factors as predictors of work disability. Recursive partitioning and causal modeling procedures were also used. RESULTS: Sample characteristics were mean age 51 years, 82% female, and 92% white. Older age (odds ratio [OR] 1.2, 95% confidence interval [95% CI] 1.1-1.4) and lower income (OR 1.7, 95% CI 1.0-2.7) predicted work disability, whereas more hours worked (OR 0.9, 95% CI 0.8-0.9) and preference to work full time (OR 0.2, 95% CI 0.1-0.4) or part time (OR 0.4, 95% CI 0.2-0.6) versus not to work were protective in the regression analysis. In recursive partitioning analyses, RA disease factors predicted work disability among older subjects, and functional limitation was the fourth most important factor. Job physical demand was not a significant or important factor. CONCLUSION: In this contemporary data from a large RA cohort, older age, lower income, fewer working hours, and preference not to work were the risk factors for work disability. The impact of disease factors was limited to subjects ages >or=56 years. Job physical demand level had little impact.

Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C, Bombardieri S, Choi H, Combe B, Dougados M, Emery P, Gomez-Reino J, Keystone E, Koch G, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Michaud K, O'Dell J, Paulus H, Pincus T, Richards P, Simon L, Siegel J, Smolen JS, Sokka T, Strand V, Tugwell P, van der Heijde D, van Riel P, Vlad S, van Vollenhoven R, Ward M, Weinblatt M, Wells G, White B, Wolfe F, Zhang B, Zink A, Felson D. · Division of Rheumatology, Medical University of Vienna, Vienna, Austria. · Ann Rheum Dis. · Pubmed #18791055 No free full text.

Abstract: OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardised operating procedures, which use a three-step approach: (1) expert-based definition of relevant research questions (November 2006); (2) systematic literature search (November 2006 to May 2007); and (3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature the expert panel recommended that each trial should report the following items: (1) disease activity response and disease activity states; (2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; (3) baseline disease activity levels (in general); (4) the percentage of patients achieving a low disease activity state and remission; (5) time to onset of the primary outcome; (6) sustainability of the primary outcome; (7) fatigue. CONCLUSIONS: These recommendations endorsed by EULAR and ACR will help harmonise the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

Zhang B, Lavalley M, Felson DT. · Clinical Epidemiology Unit, Boston University, 715 Albany Street, A203 Boston, MA 02118, USA. · Ann Rheum Dis. · Pubmed #18697778 No free full text.

Abstract: OBJECTIVE: To test whether rheumatoid arthritis (RA) trials treatment efficacy versus control is better detected for patients with lower tender joint counts (TJC) or swollen joint counts (SJC) than for higher counts. METHODS: Using data from six large multicentre trials (N = 2002) and an intent-to-treat approach at 6 months, two subtrials were created within each trial, the lower disease activity group (defined by TJC less than overall median) and the higher disease activity group. The same approach was used for SJC. Active treatment was tested for treatment control differences using several RA trial outcome measures: ACR20, EULAR response, ACRHybrid. Sample sizes needed for higher TJC and SJC RA trials versus lower TJC and SJC trials were compared. RESULTS: Subtrials of subjects with lower TJC were found to have much higher sensitivity to change than those of subjects with higher TJC across all trials and outcome measures. A trial with lower TJC patients would require a smaller sample size than those with higher TJC patients. Results were not consistent for SJC subgroups. Three reasons were found for sensitivity to change of lower TJC: compared with higher TJC, those with lower TJC showed greater response to active treatment. SUBJECTS: with higher TJC on control treatment had greater percentage improvement and more variable responses than those in the lower TJC group. CONCLUSIONS: In RA trials, patients with lower disease activity within the range of current trial eligibility are more likely to show treatment efficacy than patients with higher disease activity. Lowering thresholds especially for TJC in trials may make it easier to detect treatment effects in RA.

Allaire S, Wolfe F, Niu J, Zhang Y, Zhang B, LaValley M. · Clinical Epidemiology Research and Training Unit, Boston University, 715 Albany Street, Boston, MA 02118, USA. · Arthritis Rheum. · Pubmed #18668597 No free full text.

Abstract: OBJECTIVE: To examine the role of anti-tumor necrosis factor (anti-TNF) agents in predicting work disability in subjects with rheumatoid arthritis (RA). METHODS: We studied 953 subjects with rheumatologist-diagnosed RA from a US cohort using a nested, matched, case-control approach. Subjects provided data on medication usage and employment every 6 months for 18 months, were employed at baseline, and were age <65 years at last followup. Cases were subjects who were not employed at followup (n = 231) and were matched approximately 3:1 by time of entry into the cohort to 722 controls who were employed at followup. Risk of any employment loss, or loss attributed to RA, at followup as predicted by use of an anti-TNF agent at baseline was computed using conditional logistic regression. Stratification on possible confounding factors and recursive partitioning analyses were also conducted. RESULTS: Subjects' mean age was 51 years, 82% were female, 92% were white, and 72% had more than a high school education. Nearly half (48%) used an anti-TNF agent at baseline; characteristics of anti-TNF agent users were similar to nonusers. In the main analyses, anti-TNF use did not protect against any or RA-attributed employment loss (odds ratio [95% confidence interval] 1.1 [0.7-1.6] versus 0.9 [0.5-1.5]). However, a protective effect was found for users with disease duration <11 years (odds ratio [95% confidence interval] 0.5 [0.2-0.9]). In recursive partitioning analyses, age, RA global severity, and functional limitation played a much greater role in determining employment loss than anti-TNF agent use. CONCLUSION: Anti-TNF agent use did not protect against work disability in the main analyses. In stratified analyses, their use was protective among subjects with shorter RA duration, whereas in nonparametric analyses, age and disease factors were the prominent predictors of work disability.

Luo X, Zuo X, Zhou Y, Zhang B, Shi Y, Liu M, Wang K, McMillian DR, Xiao X. · Department of Pathophysiology, Xiangya School of Medicine, Central South University, Xiangya Road, Changsha, Hunan 410008, China. · Arthritis Res Ther. · Pubmed #18410682 links to  free full text

Abstract: INTRODUCTION: It was recently suggested that heat shock protein (HSP)70, an intracellular protein, is a potential mediator of inflammatory disease when it is released into the extracellular compartment. Although elevated HSP70 levels have been identified in rheumatoid arthritis (RA) synovial tissues and RA synovial fluid compared with patients with osteoarthritis and healthy individuals, it remains unclear what role extracellular HSP70 plays in the pathogenesis of RA. This study was conducted to investigate the effects of extracellular HSP70 on the production of RA-associated cytokines in fibroblast-like synoviocytes from patients with RA and to elucidate the mechanisms involved. METHODS: IL-6, IL-8 and monocyte chemoattractant protein (MCP)-1 levels in culture supernatants were measured using enzyme-linked immunosorbent assays. Activation of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated protein kinases (ERKs), c-Jun amino-terminal kinase (JNK) and p38 MAPK, was detected using Western blotting. Nuclear translocation of nuclear factor-kappaB (NF-kappaB) and degradation of the inhibitory protein IkappaBalpha were examined using immunohistochemistry and Western blotting. RESULTS: Human HSP70 downregulated IL-6, IL-8 and MCP-1 production in RA fibroblast-like synoviocytes induced by tumour necrosis factor (TNF)-alpha in a concentration dependent manner. HSP70 inhibited the activation of ERK, JNK and p38 MAPK in fibroblast-like synoviocytes stimulated by TNF-alpha. Furthermore, HSP70 also significantly inhibited nuclear translocation of nuclear factor-kappaB and degradation of IkappaBalpha induced by TNF-alpha. CONCLUSION: Extracellular HSP70 has an anti-inflammatory effect on RA by downregulating production of IL-6, IL-8 and MCP-1 in fibroblast-like synoviocytes, which is mediated through inhibited activation of the MAPKs and NF-kappaB signal pathways.

Felson DT, Zhang B, Siegel JN. · Clinical Epidemiology Unit, Boston University School of Medicine, 650 Albany Street, Boston, MA 02118, USA. · Ann Rheum Dis. · Pubmed #18408109 No free full text.

This publication has no abstract.

Luo X, Zuo X, Zhang B, Song L, Wei X, Zhou Y, Xiao X. · Department of Pathophysiology, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, Hunan, China. · Cell Stress Chaperones. · Pubmed #18392950 links to  free full text

Abstract: It has recently been suggested that heat shock protein (Hsp) 70, an intracellular protein, can be released into the extracellular compartment and exert important immunomodulatory functions. Although elevated Hsp70 has been found in synovial fluid from patients with rheumatoid arthritis (RA), its sources and extracellular functions remain unclear. In this study, we explored whether stress response such as heat stress or exposure to tumor necrosis factor-alpha (TNF-alpha) could induce Hsp70 release from RA fibroblast-like synoviocytes (FLSs) and whether extracellular Hsp70 would stimulate cytokine production in RA FLSs. Cultured FLSs were obtained from patients with RA. The expression of intracellular Hsp70 was studied by Western blot. Hsp70 release and the production of interleukin (IL)-6, IL-8, and IL-10 by RA FLSs were studied by specific enzyme-linked immunosorbent assays. The levels of Toll-like receptor (TLR) 2 and 4 mRNA and protein in FLSs were analyzed using reverse transcription-polymerase chain reaction and Western blotting. Treatment with sublethal heat shock or TNF-alpha results in the up-regulation of intracellular Hsp70 in FLSs and Hsp70 release from RA FLSs. In vitro studies show that extracellular Hsp70 can induce anti-inflammatory cytokine IL-10 production in FLSs. The mRNA and protein expression of TLR2 and TLR4 was demonstrated in FLSs, and TLR4 blocking abrogated the up-regulatory effects of Hsp70 on IL-10 production. Thus, these results lend support to the hypothesis that Hsp70 is actively released from FLSs in response to heat shock or TNF-alpha and Hsp70 may be a major paracrine/autocrine inducer of IL-10 production in FLSs via TLR4.

van Staa TP, Geusens P, Zhang B, Leufkens HG, Boonen A, Cooper C. · Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. · Rheumatology (Oxford). · Pubmed #16899499 links to  free full text

Abstract: OBJECTIVES: There are few data on the cost-effectiveness of bisphosphonates with oral glucocorticoids (GCs). An individual patient-based pharmaco-economic model was developed. METHODS: Data were obtained from a cohort of oral GC users aged 40+ (n = 190 000) in the UK General Practice Research Database. Individualized fracture and mortality risks were calculated specific for age, sex, daily and cumulative GC dose, indication and other clinical risk factors. UK costs of medication and direct costs of fracture were obtained from National Institute for Clinical Excellence and used to estimate costs per quality-adjusted life-year (QALY) gained and fracture prevented for bisphosphonates in patients treated for 5 yrs with GCs. RESULTS: With the use of 5 mg GCs daily, the cost per one QALY gained with bisphosphonates was 41k UK pounds (95% confidence intervals 22-72k) in women aged <60 [men 40k pounds (29-54k)], 17k pounds (13-24k) in women aged 60-79 [men 43k pounds (31-60k)], 5k pounds(3-6k) in women aged 80+ [men 35k pounds (25-46k)]. With 15 mg GC, these figures were 17k pounds (14-21k), 13k pounds (10-16k) and 15k pounds (9-26k) in women and 22k pounds (17-26k), 34 pounds (23-53k) and 33k pounds (27-42k) in men, respectively. When stratifying by overall fracture risk and life expectancy at the start of GC therapy, cost per QALY increased with decreasing life expectancy. Patients with rheumatoid arthritis had comparatively better cost-effectiveness, given higher fracture risk and better life expectancy. CONCLUSIONS: The cost-effectiveness of bisphosphonates varied substantially. Bisphosphonates can be considered cost-effective in patients with higher fracture risks, such as elderly patients (with a life expectancy over 5 yrs), and younger patients with a fracture history, low body mass index, rheumatoid arthritis or using high GC doses.

Zhang Y, Holford TR, Leaderer B, Zahm SH, Boyle P, Morton LM, Zhang B, Zou K, Flynn S, Tallini G, Owens PH, Zheng T. · Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA. · Cancer Causes Control. · Pubmed #15141141 No free full text.

Abstract: OBJECTIVE: To further investigate the role of prior medical conditions and medication use in the etiology of non-Hodgkin lymphoma (NHL), we analyzed the data from a population-based case-control study of NHL in Connecticut women. METHODS: A total of 601 histologically confirmed incident cases of NHL and 717 population-based controls were included in this study. In-person interviews were administered using standardized, structured questionnaires to collect information on medical conditions and medication use. RESULTS: An increased risk was found among women who had a history of autoimmune disorders (such as rheumatoid arthritis, lupus erythematosus, Sjogren's syndrome, and multiple sclerosis), anemia, eczema, or psoriasis. An increased risk was also observed among women who had used steroidal anti-inflammatory drugs and tranquilizers. A reduced risk was found for women who had scarlet fever or who had used estrogen replacement therapy, aspirin, medications for non-insulin dependent diabetes, HMG-CoA reductase inhibitors, or beta-adrenergic blocking agents. Risk associated with past medical history appeared to vary based on NHL subtypes, but the results were based on small number of exposed subjects. CONCLUSION: A relationship between certain prior medical conditions and medication use and risk of NHL was observed in this study. Further studies are warranted to confirm our findings.

Chukwuocha RU, Zhang B, Lai CJ, Scavulli JF, Albani S, Carson DA, Chen PP. · Department of Medicine, University of California, Los Angeles 90095-1670, USA. · J Rheumatol. · Pubmed #10405927 No free full text.

Abstract: OBJECTIVE: Previously, we showed that rheumatoid arthritis (RA) had both antibodies and T cells specific for the QKRAA-encompassing Escherichia coli dnaJ protein. These findings suggest that the bacteria induced anti-dnaJ responses may cross react with the human homolog of bacterial dnaJ in the joint, resulting in tissue damage. METHODS: We used the combinatorial library technique to isolate and characterize an IgG monoclonal anti-dnaJ antibody (designated CG1) from the blood of a patient with RA. RESULTS: Sequence analysis of CG1 revealed that its heavy and light chain V regions were respectively most homologous to the 3d279d VH4 and the O18 Vk1 genes. Interestingly, 3d279d is frequently expressed by B cells stimulated with staphylococcal enterotoxin; and O18 is the main gene employed by the Vk1 IgG antibodies against Haemophilus influenzae. CONCLUSION: The combinatorial immunoglobulin library method represents an interesting model of how to approach the isolation and characterization of antibody-like reagents in the elucidation of autoantigens in RA.

Miyachi K, Hankins RW, Uehara Y, Zhang B, Saku K, Homma Y, Shigematsu H, Mikoshiba K. · No affiliation provided · J Rheumatol. · Pubmed #19208541 No free full text.

This publication has no abstract.