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ID PMID Title PublicationDate abstract
18260496 Mechanism of failure eleven years following a Buechel Pappas hip resurfacing. 2007 Dec Hip resurfacing is gaining popularity as an acceptable treatment option for young active patients with hip osteoarthritis. The Buechel-Pappas hip resurfacing system has a titanium alloy femoral and acetabular component with a polyethylene liner. The titanium nitride coating of the femoral component has been shown to have a very low wear rate during in vivo laboratory studies. Although it has been on the marketplace since 1989, we could find no followup results in the literature. We report a rare case of Buechel-Pappas hip resurfacing which presented with catastrophic failure at 11 years follow-up. The polyethylene liner was worn through, and there was severe metallosis with extensive titanium debris. The head of the femur was however viable, suggesting that the failure of the procedure was due to the bearing surface.
16604876 [Infectious risks of immunomodulating therapies in rheumatology]. 2006 Mar 15 Corticosteroids and cytotoxic drugs form the conventional immunomodulators in rheumatology. This therapeutic arsenal has recently been widened by TNF-alpha antagonists and other anti-cytokines. If rheumatoid arthritis is itself associated with infections, immunomodulating therapies further increase the risk of infection, especially when used in combination therapies. Among conventional therapies, corticosteroids are associated with the highest risk for both common bacterial and opportunistic infections. Infliximab is the TNF-alpha antagonist associated with the highest risk of infection. Its use has been particularly associated with cases of severe tuberculosis. All patients at risk for tuberculosis, treated with corticosteroids or TNF-alpha antagonists, should therefore receive an adequate prophylaxis.
18707027 Hepatitis C virus-related arthritis. 2008 Oct Although asymptomatic joint involvement and arthralgias are frequent in patients with hepatitis C virus chronic infection (HCV), a true arthritis affects only up to 4% of the subjects. HCV-related arthritis (HCVrA) is usually distinguished in two clinical subsets: a more frequent symmetrical polyarthritis (SP), similar to rheumatoid arthritis but much less serious, and an intermittent mono-oligoarthritis (IMO) that involves medium and large sized joints, mainly the ankle. This latter subset is strictly related to the presence of HCV-induced mixed cryoglobulinemia and its cutaneous manifestations, in particular purpura. According to recent reports, anti-CCP antibodies are considered very useful in differentiating the SP subset from rheumatoid arthritis. The treatment of HCVrA is still largely empirical because few studies have analyzed this topic. However, COXIBs, NSAIDs, low doses of corticosteroids, hydroxychloroquine and less frequently methotrexate and penicillamine have been used with partial or complete control of symptoms. On the basis of recent studies, the administration of cyclosporine also seems to be sufficiently safe. The scarcely aggressive nature of HCVrA does not favour the use of anti-TNF agents. Specific anti-viral therapy (interferon-alpha+ribavirin) must be accurately evaluated because interferon-alpha can induce the development or the worsening of several autoimmune HCV-related disorders including arthritis.
17360028 Persistent chronic inflammation contributes to the development of cancer in patients with 2007 Aug OBJECTIVE: We assessed the contribution of clinical features, routine laboratory markers of inflammation, HLA-DRB1 alleles, and methotrexate therapy to cancer incidence and mortality in a cohort of rheumatoid arthritis (RA) patients prospectively followed at the single referral center for an area of Northwestern Spain. METHODS: Patients fulfilling the 1987 American College of Rheumatology classification criteria for RA seen at the rheumatology outpatient clinic of Hospital Xeral Calde, Lugo between March and September 1996 were included. HLA-DRB1 phenotype, epidemiological and clinical data from the time of RA diagnosis were assessed at that time. Afterward, patients were prospectively followed and clinical records were examined until the patient's death or September 1, 2005. Presence of histologically confirmed diagnosis of cancer was assessed over the extended follow-up in all cases. RESULTS: One hundred eighty-two consecutive patients were assessed. Compared with the general Spanish population, the age- and gender-standardized mortality ratio for cancer was 1.01 (95% confidence interval: 0.49 to 1.75). Cancer mortality adjusted by age and sex was associated with chronic inflammation determined by C-reactive protein (CRP) (hazard ratio, HR, = 1.15; P < 0.001), and erythrocyte sedimentation rate (ESR) (HR = 1.05; P = 0.006). Increased risk of cancer was also associated with CRP (HR = 1.13; P = 0.001), ESR (HR = 1.04; P = 0.02), and the HLA-DRB1*0404 allele (HR = 3.24; P = 0.05). CONCLUSION: This study does not support an increased mortality due to cancer in RA patients from Northwestern Spain. However, the present data indicate that high-grade inflammation contributes to both the risk and the mortality of cancer in RA.
17410418 Depression history, stress, and pain in rheumatoid arthritis patients. 2007 Jun This study examined the role of past episodes of depression on pain reports for patients with rheumatoid arthritis (RA) before and during stress induction. A history of major depressive episodes was assessed by diagnostic interviews for 138 RA patients, 74 who later participated in a set of laboratory procedures designed to induce interpersonal stress. Patients were evaluated by a rheumatologist and then asked to report joint and bodily pain throughout the laboratory study. We found that RA patients with a history of two or more episodes of major depression had more pain at baseline, and exhibited higher pain in response to the stress induction than did RA patients with either only one episode or no history of depression. Such findings provide new insight in the dynamic relationships between depression, stress, and pain.
18245885 [Genomic approaches to bone and joint diseases. Current status of human disease genomics i 2008 Feb Rheumatoid arthritis (RA) is an autoimmune/inflammatory disorder which causes progression of polyarticular destruction. RA is a multifactorial disorder, in which genetic and environmental factors contribute to the onset of diseases. Linkage analyses and case-control association studies in RA have identified several susceptible genes including genetic variation in human leukocyte antigen region. Here, we review major genes susceptible to RA, and discuss effects of these genes on production of anti-cyclic citrullinated peptides antibody.
17873969 Altered FOXO1 transcript levels in peripheral blood mononuclear cells of systemic lupus er 2007 Nov FOXO forkhead transcription factors play an important role in controlling lymphocyte activation and proliferation. To evaluate the possibility that FOXO transcriptional expression is dysregulated in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients, we determined the quantities of FOXO1, FOXO3a, and FOXO4 transcripts in peripheral blood mononuclear cells (PBMCs) from normal controls as well as from SLE and RA patients. Results showed that FOXO1 and FOXO3a are dominant FOXO factors at the transcript level in PBMCs. Statistical analysis showed that the FOXO1 transcript levels in RA patients and in SLE patients with active disease activity were significantly lower than those in normal controls, and the FOXO1 transcript levels were inversely correlated with lupus disease activity. In contrast, the differences in FOXO3a and FOXO4 transcript levels between normal controls and patients were not significant. These data suggest that the transcriptional dysregulation in FOXO1 is possibly linked to the pathogenesis of SLE and RA.
17457438 Increased serum anti-mycobacterial antibody titers in rheumatoid arthritis patients. Is th 2007 May OBJECTIVE: To investigate the presence of immunoreactivity against mycobacterial antigens in the sera of patients with rheumatoid arthritis (RA) and to detect the target of the immune reaction. METHODS: This study was carried out on 60 patients with RA, and 25 patients with no joint diseases in the laboratory of Clinical Microbiology Department of Ankara University Medical Faculty, Ankara, Turkey between July 2003 to January 2004. Secreted and cellular antigens of Mycobacterium tuberculosis (M. tuberculosis) H37Rv and Mycobacterium bovis (M. bovis) were isolated and purified by high performance liquid chromatography to antigenic fractions. The immunoreactivity of patient and control sera against these antigens were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Immunoreactivity against mycobacterial antigens in RA patients were significantly higher than controls. Significant difference between patients and controls has been determined with M. bovis Bacillus Calmette Guerin (BCG) culture fluid and sonicate antigens, but not with M. tuberculosis H37Rv. This suggests that the antigen triggering immune response in patients with RA may belong to or mainly expressed on M. bovis BCG. The ELISA results showed significant difference between RA patients and controls with all antigenic fractions. CONCLUSION: Presence of increased immunoreactivity against mycobacterial antigens in the sera of patients with RA was detected. When statistical analyses was considered, we cannot put forward any antigenic fraction alone as the one responsible for the increased reactivity.
17644541 Assessment of rituximab's immunomodulatory synovial effects (ARISE trial). 1: clinical and 2008 Mar OBJECTIVE: Treatment with the anti-CD20 monoclonal antibody (mAb) rituximab is effective in rheumatoid arthritis (RA). Marked depletion of circulating B cells, seen in almost all patients, does not correlate with efficacy. The potential synovial immunomodulatory effects of rituximab have not been fully defined. METHODS: The ARISE trial is an open label, serial synovial biopsy (pre-treatment and 8 weeks) study of rituximab, given 1 g intravenously on days 0 and 14 without peri-infusional steroids, in active RA patients on concomitant methotrexate (MTX). Synovial tissue was analysed by immunohistochemistry with digital image analysis and gene expression by real-time PCR. RESULTS: The mean (SD) baseline DAS28 score was 6.5 (0.4), and mean MTX dose 17.3 mg/week. Of 13 patients, 11 had failed prior tumour necrosis factor (TNF) inhibitor therapy. With treatment, all patients experienced near complete depletion of circulating B cell numbers. During the 6 months after treatment, 7/13 patients achieved an American College of Rheumatology (ACR) 20% improvement (ACR20) response, 3/13 an ACR50 response and 2/13 an ACR70 response. There was a significant decrease in synovial B cells after treatment, but only a small trend towards greater reduction among clinical responders. Among the three patients with ACR50 responses there was a significant decrease in synovial immunoglobulin synthesis. CONCLUSIONS: These data suggest that unlike those in circulation, synovial B cells are decreased but are not eliminated by rituximab therapy. Patients with higher levels of response may have more consistent depletion of synovial B cells, and may also have an alteration in synovial B cell function, as indicated by decreases in synovial immunoglobulin synthesis. Thus, effects on synovial B cells may be necessary but not sufficient for inducing clinical efficacy. Other effects, such as on primary lymph organ B cell antigen presentation or cytokine production, may be operative.
17444955 The influence of MHC class II molecules containing the rheumatoid arthritis shared epitope 2007 May Aggrecan has been implied as an autoantigen in rheumatoid arthritis (RA). Immunization with aggrecan induces arthritis in BALB/c (H-2(d)) mice but not in other strains of mice [e.g. C57BL/6 (H-2(b))]. In humans, the strongest genetic association with RA is to the shared epitope (SE), and aggrecan peptides are predicted to bind to the SE. Therefore, we hypothesized that C57BL/6 mice transgenic (tg) for the RA SE (DR4 tg mice) may be susceptible to aggrecan-induced arthritis. C57BL/6 and DR4 tg mice were immunized with a mixture of SE-binding aggrecan peptides and tested for immune responses to the corresponding peptides as well as aggrecan. Sustained T- and B-cell immune responses to aggrecan and several of its peptides were detected in DR4 tg mice. C57BL/6 mice showed only transient T-cell responses to different immunizing peptides and little B-cell response. Therefore, an immune response to peptides of aggrecan can be induced experimentally in DR4 tg mice as anticipated from the predicted and actual binding affinities of these peptides for the RA SE. Failure to induce arthritis in these DR4 tg mice may be due to a lack of appropriate non-MHC genes.
18455949 Disease status, costs and quality of life of patients with rheumatoid arthritis in France: 2008 Jul OBJECTIVE: To investigate resource consumption and quality of life (utility) in a sample of patients covering the full spectrum of the disease, modalities of patient management and geographic areas. METHODS: Information on demographics, disease parameters, work capacity and resource consumption (in the past 1, 3 or 12 months depending on the resource) was collected in an anonymous mail survey from all members of a national patient association (ANDAR). Results are presented for the sample and by level of functional capacity, in 2005 euro. RESULTS: 1487 patients were included in the analysis (response rate 49%). Mean age was 62.7 years and 83.5% of respondents were female. Mean disease duration was 18 years; mean HAQ was 1.42; fatigue and pain ranked 5.6 and 4.8 on a scale between 0 and 10, respectively. Of patients below 60 years, 34% had taken early retirement due to RA, and only 15% of patients with a HAQ of 2 or higher were working. Productivity losses were estimated at 5076 euro, of which indemnity payments covered 1944 euro. Direct health care costs were 11,757 euro in the societal perspective and 9216 euro in the perspective of the national health insurance. Direct non-medical costs (including informal care) were 4857 euro and 136 euro respectively. Costs to society increased from 9400 euro in mild disease to 40,700 euro in severe disease, and to public payers from 6000 euro to 19,000 euro. Utility decreased simultaneously from 0.80 to 0.06. CONCLUSION: The study confirms overall findings in other studies in other countries, and provides the first estimate of all costs by disease severity in France.
16443164 Homocysteine from endothelial cells promotes LDL nitration and scavenger receptor uptake. 2006 Feb 1 We recently reported that methionine-loaded human umbilical vein endothelial cells (HUVECs) exported homocysteine (Hcy) and were associated with hydroxyl radical generation and oxidation of lipids in LDL. Herein we have analysed the Hcy-induced posttranslational modifications (PTMs) of LDL protein. PTMs have been characterised using electrophoretic mobility shift, protein carbonyl ELISA, HPLC with electrochemical detection and Western blotting of 3-nitrotyrosine, and LDL uptake by scavenger receptors on monocyte/macrophages. We have also analysed PTMs in LDL isolated from rheumatoid (RA) and osteo-(OA) arthritis patients with cardiovascular disease (CVD). While reagent Hcy (< 50 microM) promoted copper-catalysed LDL protein oxidation, Hcy released from methionine-loaded HUVECs promoted LDL protein nitration. In addition, LDL nitration was associated with enhanced monocyte/macrophage uptake when compared with LDL oxidation. LDL protein nitration and uptake by monocytes, but not carbonyl formation, was elevated in both RA and OA patients with CVD compared with disease-matched patients that had no evidence of CVD. Moreover, a direct correlation between plasma total Hcy (tHcy) and LDL uptake was observed. The present studies suggest that elevated plasma tHcy may promote LDL nitration and increased scavenger receptor uptake, providing a molecular mechanism that may contribute to the clinical link between CVD and elevated plasma tHcy.
16490910 Preclinical carotid atherosclerosis in patients with rheumatoid arthritis. 2006 Feb 21 BACKGROUND: Rheumatoid arthritis is associated with increased morbidity and mortality because of cardiovascular disease, independent of traditional risk factors. OBJECTIVE: To determine the prevalence of preclinical atherosclerosis in patients with rheumatoid arthritis and to identify clinical and biological markers for atherosclerotic disease in this patient population. DESIGN: Matched, cross-sectional study. SETTING: Hospital for Special Surgery in New York City. PATIENTS: 98 consecutive outpatients with rheumatoid arthritis who were followed by rheumatologists and 98 controls matched on age, sex, and ethnicity. MEASUREMENTS: Cardiovascular risk factor ascertainment and carotid ultrasonography in all participants; disease severity, disease treatment, and inflammatory markers in patients with rheumatoid arthritis. RESULTS: Despite a more favorable risk factor profile, patients with rheumatoid arthritis had a 3-fold increase in carotid atherosclerotic plaque (44% vs. 15%; P < 0.001). The relationship between rheumatoid arthritis and carotid atherosclerotic plaque remained after accounting for age, serum cholesterol levels, smoking history, and hypertensive status; adjusted predicted prevalence was 7.4% (95% CI, 3.4% to 15.2%) for the control group and 38.5% (CI, 25.4% to 53.5%) for patients with rheumatoid arthritis. Age (P < 0.001) and current cigarette use (P < 0.014) were also significantly associated with carotid atherosclerotic plaque. Among patients with rheumatoid arthritis, atherosclerosis was related to age, hypertension status, and use of tumor necrosis factor-alpha inhibitors (a possible marker of disease severity). LIMITATIONS: The study had a cross-sectional design, and inflammatory markers were determined only once. CONCLUSIONS: Patients with rheumatoid arthritis have a high prevalence of preclinical atherosclerosis independent of traditional risk factors, suggesting that chronic inflammation and, possibly, disease severity are atherogenic in this population.
17590885 The influence of medication beliefs and other psychosocial factors on early discontinuatio 2007 Sep OBJECTIVE: Although drug survival time might be a better measure of clinical effectiveness than drug adherence, there is little research literature in this area, in particular about the influence of medication beliefs and psychosocial factors. This study aimed to investigate the above relationships using patients who were newly diagnosed with rheumatoid arthritis (RA). METHODS: Sixty-eight RA patients starting their first disease-modifying anti-rheumatic drug (DMARD) were interviewed shortly after initiating therapy, and then one year later. Before each meeting, patients were asked to complete a set of questionnaires, including Beliefs about Medication, Spielberger State-Trait Anxiety Inventory - Short Form, the modified Stanford Health Assessment Questionnaire, Beck Depression Inventory-1 and the Significant Others Scale. Relevant sociodemographic background, disease activity and drug history were obtained. Clinical measures such as grip strength and joint count were assessed. RESULTS: A stepwise logistic regression analysis was applied to two patient groups: those who continued taking their DMARD one year later, and those who did not. No significant difference between the groups for levels of disability and disease activity were found. Only age and anxiety emerged as significant predictors of drug discontinuation at 52 weeks. CONCLUSIONS: Contrary to expectation, this study demonstrated that older and less anxious patients were more likely to discontinue taking their initial DMARD within the first year. The study may have implications for counselling older and less anxious patients prior to DMARD therapy. However, there are limitations in generalizing the results because of the small population sample. It also did not take into account drug intolerance as a pertinent factor for early drug discontinuation.
17148544 Changes in macrophage function after rituximab treatment in patients with rheumatoid arthr 2007 Jun OBJECTIVE: To assess changes in macrophage phenotype and function after rituximab-induced B cell depletion in patients with rheumatoid arthritis (RA). METHODS: 10 patients with RA were treated with rituximab, achieving significant B cell depletion 4 months later. Clinical improvement, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, mRNA of B cell activating factor (BAFF), interleukin (IL) 10 and CD86 in human monocyte-derived macrophages (HMDMs) and tumour necrosis factor alpha (TNFalpha) secretion from cultured HMDMs were assessed at baseline and after the depletion. RESULTS: A clinical response of American College of Rheumatology (ACR) 50% improvement was noted in six patients, and another two patients responded with moderate improvement, equivalent to ACR 20-50% improvements. RF and anti-CCP antibodies were positive at baseline in seven of ten patients. RF disappeared or declined in six patients 4 months after treatment, correlating with clinical improvement. By contrast, anti-CCP remained unchanged in six patients. After rituximab treatment, and in association with clinical improvement, BAFF, IL10 and CD86 mRNA expression in HMDM were significantly upregulated compared with values at baseline. A significant decrease in TNFalpha in the supernatant of cultured HMDM was also noted. CONCLUSIONS: In addition to B cell depletion and attenuation in some of the specific autoantibodies, clinical improvement in rituximab-treated patients with RA occurred in association with changes in macrophage function.
17694271 Septic arthritis of the right ankle caused by Staphylococcus aureus infection in a rheumat 2007 We report on a 65-year-old man with rheumatoid arthritis who developed septic arthritis of the right ankle and was treated with etanercept, low-dosage prednisolone, and salazosulfapyridine for 18 weeks. Staphylococcus aureus was cultured from ankle synovial fluid; hence, etanercept was stopped and cefazolin was administered. The patient responded well to arthroscopic synovectomy and irrigation of the ankle. Etanercept treatment should cease if it leads to septic arthritis and patients should be prescribed systemic antibiotics, with surgical debridement considered.
18391064 Arthritis induced by posttranslationally modified (citrullinated) fibrinogen in DR4-IE tra 2008 Apr 14 Rheumatoid arthritis (RA) is a common autoimmune disease that afflicts the synovium of diarthrodial joints. The pathogenic mechanisms inciting this disease are not fully characterized, but may involve the loss of tolerance to posttranslationally modified (citrullinated) antigens. We have demonstrated that this modification leads to a selective increase in antigenic peptide affinity for major histocompatibility complex (MHC) class II molecules that carry the RA-associated shared epitope, such as HLA-DRB1*0401 (DR4). We describe the induction of arthritis in DR4-IE transgenic (tg) mice with citrullinated fibrinogen, a protein commonly found in inflamed synovial tissue and a frequent target of autoantibodies in RA patients. The disease induced in these mice was characterized by synovial hyperplasia followed by ankylosis, but lacked a conspicuous polymorphonuclear cell infiltrate. Immunological analysis of these mice through T cell epitope scanning and antibody microarray analysis identified a unique profile of citrulline-specific reactivity that was not found in DR4-IE tg mice immunized with unmodified fibrinogen or in wild-type C57BL/6 mice immunized with citrullinated fibrinogen, two conditions where arthritis was not observed. These observations directly implicate citrullinated fibrinogen as arthritogenic in the context of RA-associated MHC class II molecules.
18412305 Patients with scleroderma may have increased risk of osteoporosis. A comparison to rheumat 2008 Jun OBJECTIVE: To investigate if subjects with scleroderma (systemic sclerosis, SSc) have increased risk for developing osteoporosis (OP). METHODS: A survey assessing demographics, diagnosis/investigations for OP, and risk factors for OP was mailed to 129 patients with SSc, 158 controls with noninflammatory musculoskeletal (MSK) disease, and 230 positive controls with rheumatoid arthritis (RA). All available charts were reviewed and results were included in analyses of demographics, OP status, past bone mineral density (BMD), and past steroid use. In addition, we recorded BMD results (T score) of SSc patients with their matched RA controls. Analyses adjusted for age were done for SSc versus MSK and SSc versus RA. RESULTS: The response rate was 61% for patients with SSc (n = 28 diffuse, 51 limited disease), RA 67%, and MSK 59%; however, through chart review, 159 SSc, 140 MSK, and 235 RA patients were included in the analyses. Mean age and proportion of women did not differ between groups. Disease duration was longer in RA versus SSc group (16.5 vs 11.5 yrs; p < 0.0001). The prevalence of OP in SSc was similar to RA controls (19.4% vs 16.7%; p = 0.38) but likely higher than MSK controls (12.2%; p = 0.054). Subjects with SSc reported a higher rate of disability (41.0% vs 15.6%; p = 0.0001) and less family history of OP (22.8% vs 46.7%; p = 0.0006) compared with the MSK control group. There were no differences between groups in reports of fracture (35% SSc, 43% MSK, 37% RA; p = 0.5) or OP related fractures (4% SSc, 11% MSK, 11% RA; p = 0.5). Subjects with SSc were less likely to have had a BMD done in the past compared to RA (40.9% vs 62.6%; p = 0.0001). Subjects with RA who reported OP had longer disease duration than RA without OP (18 +/- 1.7 yrs vs 12 +/- 0.8; p = 0.0009). Results from the chart review showed that the T scores of SSc (n = 56, mean age 62.9 +/- SD 10.1 yrs) at lumbar spine (SSc -1.01 vs RA -0.97), femoral neck (SSc -2.07 vs RA -1.46; p = 0.01, adjusting for age p = 0.26), and total hip region (SSc -1.52 vs RA -1.25) were comparable to or even lower than the RA group (n = 56, mean age 62.2 +/- SD 10.7 yrs). CONCLUSION: The prevalence of OP in patients with SSc was comparable to those with RA, but higher than in the MSK group. Age was found to be an important factor, as expected. Also, our results indicated that BMD (T score) in SSc was similar to or even lower than in patients with RA. Increasing the awareness to order BMD measurements in patients with SSc may be warranted based on our results, especially for older patients.
16542376 Antibody targeting of TIRC7 results in significant therapeutic effects on collagen-induced 2006 Apr TIRC7 is a cell surface molecule which is expressed in T and B lymphocytes and negatively regulates their function. Anti-TIRC7 specific monoclonal antibody (mAb) inhibited T cell memory response to recall antigens. Up-regulation of TIRC7 on lymphocytes from joint tissue of patients with Rheumatoid Arthritis (RA) and mice with collagen induced arthritis (CIA) suggested TIRC7 as a novel target to promote anti-inflammatory reaction. Anti-TIRC7 mAb administration significantly inhibited the induction and progression of CIA and the anti-collagen IgG1 and IgG2a antibody response. Combination therapy of anti-TIRC7 mAb and soluble TNF-alpha receptor demonstrated an increased inhibitory effect over the single compounds on CIA. The results demonstrate the therapeutic potential of TIRC7 targeting with mAb in diseases associated with exaggerated T and B cell responses.
18465452 The HLA-DRB1 shared epitope is not associated with antibodies against cyclic citrullinated 2008 May OBJECTIVE: Rheumatoid arthritis (RA) is a destructive autoimmune polyarthritis that has been associated with a group of human leucocyte antigen (HLA)-DRB1 alleles that share a common amino-acid sequence at residues 70-74 called the shared epitope (SE). Recently, anti-cyclic citrullinated peptide (CCP) antibodies have also been reported to be associated with HLA-DR4 and have gained wide acceptance as early diagnostic markers for RA in Caucasian patients. The current study was performed to investigate whether the association between the SE (HLA-DRB1 0401/04/05/10) and anti-CCP antibodies is also present in Chinese Han patients with RA. METHODS: One hundred and four RA patients and 122 healthy controls were recruited. HLA-DR4 was detected by the sequence-specific primer polymerase chain reaction (SSP-PCR) phototyping method. Anti-CCP antibodies and immunoglobulin M rheumatoid factor (IgM-RF) were measured by enzyme-linked immunosorbent assay (ELISA) and laser nephelometry, respectively. RESULTS: Of the Chinese patients with RA, 76.5% exhibited anti-CCP antibodies compared with none of the controls (76.5% vs. 0%, p<0.001). The prevalence of the SE was significantly higher in patients with RA compared with controls [p = 0.010, odds ratio (OR) = 2.42, 95% confidence interval (CI) = 1.16-5.07]. Among the HLA-DR4 alleles, the presence of HLA-DRB1 0401 was significantly higher in RA patients than in controls (p = 0.0118, OR = 9.68, 95% CI = 1.13-448.8). In our study we found that the SE was not associated with production of anti-CCP antibodies (p = 0.2899, OR = 1.920, 95% CI = 0.52-8.89). CONCLUSIONS: The prevalence of the SE is significantly lower in Chinese RA patients, as compared with previous reports of a study using a Caucasian cohort, indicating that distinct genetic risk factors might be associated with anti-CCP antibody production. These data emphasized the complexity of the genetic effects of the major histocompatibility complex on the RA phenotype.