Severe extra-articular disease manifestations are associated with an increased risk of first ever cardiovascular events in patients with rheumatoid arthritis

BACKGROUND: Rheumatoid arthritis is associated with increased cardiovascular mortality and morbidity. OBJECTIVE: To assess the effect of severe extra-articular rheumatoid arthritis (ExRA) manifestations on the risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis. METHODS: Patients with ExRA (n = 81) according to predefined criteria and controls (n = 184) without evidence of extra-articular disease were identified from a large research database of patients with rheumatoid arthritis. In a structured review of the medical records, the occurrence and the date of onset of clinically diagnosed CVD events were noted. Cox proportional hazards models were used to estimate the effect of ExRA on the risk of first ever CVD events after the diagnosis of rheumatoid arthritis. ExRA manifestations were modelled as time-dependent covariates, with adjustment for age, sex and smoking at the diagnosis of rheumatoid arthritis. Onset of erosive disease and rheumatoid factor seropositivity were entered as time-dependent variables. Patients were followed until onset of CVD, death or loss to follow-up. RESULTS: ExRA was associated with a significantly increased risk of first ever CVD events (p<0.001), and also with an increased risk of new-onset coronary artery disease, adjusted for age, sex and smoking (hazard ratio (HR): 3.16; 95% confidence interval (95% CI: 1.58 to 6.33). The association between ExRA and any first ever CVD event remained significant when controlling for age, sex, smoking, rheumatoid factor and erosive disease (HR: 3.25; 95% CI: 1.59 to 6.64). CONCLUSION: Severe ExRA manifestations are associated with an increased risk of CVD events in patients with rheumatoid arthritis. This association is not due to differences in age, sex, smoking, rheumatoid factor or erosive joint damage. It is suggested that systemic extra-articular disease is a major determinant of cardiovascular morbidity in rheumatoid arthritis.     

Prognostic factors for remission in early rheumatoid arthritis: a multiparameter prospective study

OBJECTIVE: To determine prognostic factors for remission in early rheumatoid arthritis. METHODS: 191 patients with rheumatoid arthritis whose disease duration was less than one year were followed up prospectively for five years. Remission, defined by a disease activity score (DAS) of <1.6, was used as the outcome measure. Baseline clinical, laboratory, genetic, and radiographic data (with radiographic scores determined by Sharp's method, modified by van der Heijde) were obtained. RESULTS: 48 patients (25.1%) fulfilled the remission criteria at the three year follow up visit, and 30 (15.7%) at three and five years. On univariate analysis by Fisher's exact test, remission at three years and persistent remission at five years were closely correlated with baseline DAS values, C reactive protein level, Ritchie score, health assessment questionnaire score, duration of morning stiffness, and to a lesser extent baseline total radiological scores and rheumatoid factor negativity. No significant correlation was found with sex, age, extra-articular manifestations, erythrocyte sedimentation rate, anti-cyclic citrullinated protein antibodies, anti-keratin antibodies, anti-HSP 90, anticalpastatin antibodies, antinuclear antibodies, or HLA-DRB1* genotypes. Logistic regression analysis showed that the baseline independent variables predictive of remission were low DAS, Ritchie score, morning stiffness duration, and total radiographic score. CONCLUSIONS: Baseline prognostic factors for remission in early rheumatoid arthritis were mainly clinical markers of disease activity and radiological scores.     

Anticardiolipin antibodies in patients with rheumatic diseases

Recent attention has focused on the presence of anticardiolipin (ACL) antibodies and their possible role in recurrent thrombosis and abortions in patients with systemic lupus erythematosus. We analyzed ACL antibodies in 243 consecutive patients to determine their frequency in patients with different rheumatic disorders. A significantly elevated frequency was found in patients with systemic lupus erythematosus (38%), rheumatoid arthritis (33%), and psoriatic arthritis (28%). No correlation could be found between ACL antibody levels and recurrent thrombosis. In patients with rheumatoid arthritis there was a significant correlation between ACL antibodies and a history of repeated abortions. No significant association was found between ACL antibodies and other autoantibodies except in patients with rheumatoid arthritis; ACL antibody-positive rheumatoid arthritis patients were much more likely to be antinuclear antibody-positive (P less than 0.0002).     

Impact of parental history on patients' cardiovascular mortality in rheumatoid arthritis

BACKGROUND: Patients with rheumatoid arthritis are at increased risk of death from cardiovascular disease (CVD). This risk is influenced by the inflammatory activity of the rheumatoid arthritis as well as by traditional risk factors for CVD. However, little is known about whether or to what extent hereditary factors for CVD contribute additional risk in patients with rheumatoid arthritis. OBJECTIVE: To assess the clinical impact of a parental history of CVD in patients with rheumatoid arthritis. METHODS: Population based cohort study of 10,805 Swedish patients with rheumatoid arthritis aged 16-67 years during follow up (1990-2000). Parents, and cardiovascular deaths among patients and parents, were identified through register linkages. Relative risk of death v the general population was assessed using standardised mortality ratios (SMR), which were compared by Poisson regression. RESULTS: Rheumatoid patients with a parental history of fatal CVD had an SMR of death from CVD of 2.9 (95% confidence interval, 2.5 to 3.4). By contrast, rheumatoid patients without a parental history of fatal CVD had an SMR of 1.7 (1.2 to 2.3). A parental death from CVD was associated with a 70% increase in the risk of fatal CVD in rheumatoid arthritis (SMR ratio = 1.7 (1.2 to 2.4), and an increase in the 10 year mortality from CVD from 5% to 10% in men and from 2% to 4% in women aged 50 to 67 years. CONCLUSIONS: Parental history of death from CVD is an important (and easily assessable) risk factor for fatal CVD in rheumatoid arthritis.     

High Sodium Intake Is Associated With Self-Reported Rheumatoid Arthritis: A Cross Sectional and Case Control Analysis Within the SUN Cohort

Sodium intake is a potential environmental factor for immune-mediated inflammatory diseases. The aim of this study is to investigate the association of sodium intake with rheumatoid arthritis.We performed a cross-sectional study nested in a highly educated cohort investigating dietary habits as determinants of disease. Daily sodium intake in grams per day was estimated from a validated food frequency questionnaire. We identified prevalent self-reported cases of rheumatoid arthritis. Logistic regression models were used to estimate the odds ratio for rheumatoid arthritis by sodium intake adjusting for confounders. Linear trend tests and interactions between variables were explored. Sensitivity analyses included age- and sex-matched case–control study, logistic multivariate model adjusted by residuals, and analysis excluding individuals with prevalent diabetes or cardiovascular disease.The effective sample size was 18,555 individuals (mean age 38-years old, 60% women) including 392 self-reported rheumatoid arthritis. Median daily sodium intake (estimated from foods plus added salt) was 3.47 (P_25–75: 2.63–4.55) grams. Total sodium intake in the fourth quartile showed a significant association with rheumatoid arthritis (fully adjusted odds ratio 1.5; 95% CI 1.1–2.1, P for trend = 0.02). Never smokers with high sodium intake had higher association than ever smokers with high sodium intake (P for interaction = 0.007). Dose-dependent association was replicated in the case–control study.High sodium intake may be associated with a diagnosis of rheumatoid arthritis. This confirms previous clinical and experimental research.     

Effect of cardiac rehabilitation and statin treatment on anti-HSP antibody titers in patients with coronary artery disease after percutaneous coronary intervention

Accumulating evidence suggests that higher antibody titers to heat shock proteins (HSPs) are associated with the development and severity of atherosclerosis. The aim of this study was to evaluate the impact of cardiac rehabilitation therapy (CRT) or stain treatment (STT) or a combination of both (COM) on anti-HSP antibodies in patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). Clinical evaluation of subjects was performed both at the commencement and completion of the 14 weeks of treatment. CRT consisted of a supervised 6 weeks of exercise following hospital discharge and 8 weeks of home stay exercise. Patients assigned to statin therapy were treated with 80 mg per day of fluvastatin. Blood samples from 39 patients were analyzed for antibodies to HSP60 and HSP70 by ELISA. Biochemical parameters, including lipids, high-sensitivity C reactive protein (hsCRP), and interleukin-6 (IL-6), were also analyzed. We found that CRT and COM reduced antibody titers to HSP60 and HSP70 in CAD patients (by 3.79 and 10.00% of anti-HSP60, and by 5.74 and 3.45% of anti-HSP70, respectively) but statin treatment reduced only antibody titers to HSP70 (by 3.83%). There was a significant correlation between antibody titers to HSP60 versus HSP70. Considering the fact that antibody titers to HSPs are associated with the autoimmune process in CAD, CRT and COM have greater effects on reduction in autoimmune reaction after PCI than statin treatment. This reduction was accompanied by greater improvements in blood biochemical variables, such as lipids, hsCRP, and IL-6 after CRT and COM.     

Prediction of radiological outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP)

OBJECTIVE: To investigate the role of anti-cyclic citrullinated peptide antibody (anti-CCP) for the prediction of radiological outcome in patients with early rheumatoid arthritis. METHODS: Anti-CCP was assessed at baseline in 379 patients with early rheumatoid arthritis (disease duration <1 year). Radiological joint damage and progression were assessed by Larsen score after two years of follow up (end point) and used as outcome variables. The prognostic value of anti-CCP and other demographic and disease related baseline variables were assessed by univariate and multivariate analyses, including calculation of odds ratios (OR), predictive values, and multiple logistic regression models. RESULTS: The presence of anti-CCP was associated with significantly higher Larsen score both at baseline and at end point. Univariate predictor analysis showed that anti-CCP had the highest significant OR for radiological joint damage and progression after baseline Larsen score, followed by rheumatoid factor, erythrocyte sedimentation rate (ESR), C reactive protein, age, smoking status, and sex. In stepwise multiple regression analyses, baseline Larsen score, anti-CCP, and ESR were selected as significant independent predictors of the radiological outcomes. CONCLUSIONS: There is good evidence for an association of anti-CCP with radiological joint changes in rheumatoid arthritis. Anti-CCP is an independent predictor of radiological damage and progression. Though prediction in early rheumatoid arthritis is still far from perfect, the use of anti-CCP in clinical practice should make it easier for rheumatologists to reach judicious treatment decisions.     

Association of the HLA-DRB1 gene with premature death, particularly from cardiovascular disease, in patients with rheumatoid arthritis and inflammatory polyarthritis

OBJECTIVE: To examine the role of the variants of the PTPN22 and HLA-DRB1 genes as predictors of mortality in inflammatory polyarthritis (IP) and rheumatoid arthritis (RA). METHODS: Patients were recruited from a primary care-based inception cohort of patients with IP and were followed up prospectively. For patients who died, the cause and date of death was obtained. Cox proportional hazards regression models were used to assess the association of the HLA-DRB1 (including the shared epitope [SE]) and PTPN22 genes with the risk of death from all causes and from cardiovascular disease (CVD) and to assess the interactions between SE, smoking, and anti-cyclic citrullinated peptide (anti-CCP) status, adjusted by age at symptom onset and sex. RESULTS: DNA samples were available from 1,022 IP patients. During followup, 751 of them (74%) satisfied the American College of Rheumatology 1987 criteria for RA, and 242 of them (24%) died. Carriage of 2 copies of SE alleles predicted death from all causes (hazard ratio [HR] 1.57 [95% confidence interval (95% CI) 1.1-2.2]) and from CVD (HR 1.68 [95% CI 1.1-2.7]). This effect was most marked for individuals with the HLA-DRB1*01/*04 combination. An interaction of smoking, SE alleles, and anti-CCP antibodies was observed and was associated with the greatest risk of death from CVD (HR 7.81 [95% CI 2.6-23.2]). No association of the PTPN22 gene with mortality was detected. CONCLUSION: SE alleles, particularly compound heterozygotes, are associated with death from all causes and from CVD, independently of autoantibody status. However, the combination of SE, smoking, and anti-CCP antibodies is associated with a high risk of premature death in patients with IP and RA, which raises the possibility of a targeted strategy to prevent CVD in these patients.     

Antibodies Against Double-stranded RNA in Patients with Rheumatoid Arthritis, Osteoarthrosis and Paget's Disease of Bone

Abstract: Using a liquid phctse radioimmunoassay to detect antibodies to ³H-labelled double-stranded RNA the premise that rheumatoid arthritis and Paget's disease of the bone may be associated with a chronic virus disease was examined. About 33% of patients with rheumatoid arthritis had antibody levels above the normal range and 11 % had antibody levels below the normal range of controls (blood bank donors). The low binding activities were
attributed to the action of a nuclease that degraded the dsRNA. Some patients with Paget's disease of bone had higher binding activities than the normal range and similar binding activity was also found in patients with osteoarthrosis. The increase in antibodies to double-stranded RNA did not correlate with increasing age.     

Metabolic syndrome is common among middle-to-older aged Mediterranean patients with rheumatoid arthritis and correlates with disease activity: a retrospective, cross-sectional, controlled, study

OBJECTIVES: Patients with rheumatoid arthritis have an increased risk for cardiovascular disease (CVD). The prevalence of metabolic syndrome (MetS)-a major contributor to CVD-in a cohort of patients with rheumatoid arthritis and its relationship with rheumatoid arthritis related factors is investigated here. METHODS: 200 outpatients with rheumatoid arthritis (147 women and 53 men), with a mean (standard deviation (SD)) age of 63 (11) years, and 400 age and sex-matched controls were studied. MetS was assessed according to the adult treatment panel III criteria and rheumatoid arthritis disease activity by the disease activity score of 28 joints (DAS28). A standard clinical evaluation was carried out, and a health and lifestyle questionnaire was completed. RESULTS: The overall prevalence of MetS was 44% in patients with rheumatoid arthritis and 41% in controls (p = 0.5). Patients with rheumatoid arthritis were more likely to have low high-density lipoprotein cholesterol compared with controls (p = 0.02), whereas controls were more likely to have increased waist circumference or raised blood pressure (p = 0.001 and 0.003, respectively). In multivariate logistic regression analysis adjusting for demographics and rheumatoid arthritis treatment modalities, the risk of having moderate-to-high disease activity (DAS28>3.2) was significantly higher in patients with MetS compared with those with no MetS components (OR 9.24, 95% CI 1.49 to 57.2, p = 0.016). CONCLUSION: A high, albeit comparable to the control population, prevalence of MetS was found in middle-to-older aged patients with rheumatoid arthritis. The correlation of rheumatoid arthritis disease activity with MetS suggests that the increased prevalence of coronary heart disease in patients with rheumatoid arthritis may, at least in part, be attributed to the inflammatory burden of the disease.     

Arthritis of the large joints - in particular, the knee - at first presentation is predictive for a high level of radiological destruction of the small joints in rheumatoid arthritis

OBJECTIVE: To investigate the predictive value of the distribution of inflamed joints at first presentation for the severity of the disease course in rheumatoid arthritis (RA). METHODS: Of the 1009 consecutive patients included in the Leiden Early Arthritis Clinic (Leiden, The Netherlands), 285 patients fulfilled the American College of Rheumatology criteria for RA within 1 year of follow-up. Of these, 28 patients achieved remission. Radiographs of hands and feet were scored according to the Sharp-van der Heijde method, and the 28 patients with the most destructive disease were selected. The distribution of inflamed joints of the patients with the extreme disease courses was compared. The association between the distribution of inflamed joints and the level of destruction of the joints of hands and feet in the whole group of patients with RA was assessed using regression analysis. RESULTS: Comparison of patients with extreme disease courses using univariate and logistic regression analyses showed that arthritis of the large joints - in particular, the knee - was associated with severe RA. In the whole group of patients with RA, the total number of swollen joints and the presence of knee arthritis were associated independently with the level of destruction of the small joints. Patients with RA with knee arthritis had higher C reactive protein (CRP) levels than patients without knee arthritis, and investigating the distribution of inflamed joints together with other variables yielded the number of swollen joints, CRP, presence of anti-cyclic citrullinated peptide antibodies and symptom duration as predictors for severity of RA. CONCLUSION: Arthritis of large joints - in particular, the knee - at first presentation is associated with a destructive course of RA.     

Microalbuminuria in rheumatoid arthritis in the post penicillamine/gold era: association with hypertension,but not therapy or inflammation

Rheumatoid arthritis (RA) associates with excess cardiovascular (CV) morbidity and mortality. New screening tools are needed to better identify patients at increased CV risk. Microalbuminuria (MA) has been shown to associate with inflammation and future cardiovascular disease (CVD). In the present study, we assessed the prevalence of MA in a secondary care cohort of RA patients, aimed to identify factors associated with its presence and addressed its relationship to CVD and the metabolic syndrome (MetS). A total of 342 RA patients were studied. MA was defined as an albumin-creatinine ratio ≥22 (males) or ≥31 (females) milligrams per gram creatinine. The independence of the associations of MA was evaluated using binary logistic regression analysis. Prevalence of MA was 11.9%. Subjects with MA had increased prevalence of hypertension (HT), insulin resistance and type 2 diabetes. In binary logistic regression, only HT (OR = 5.22, 95%CI: 1.51–18.07, p = 0.009) was significantly associated with MA. There was no association between prevalent CVD and MA, but patients with MA had twofold increased odds of having the MetS. MA is relatively common in RA patients and is independently associated with the presence of HT. Given the association of MA with MetS, future prospective studies are needed to establish the use of MA as a screening tool for RA patients at increased CVD risk.     

Prevalence of anti cyclic citrullinated peptide antibodies in Malaysian rheumatoid arthritis patients and its correlation with disease activity

Aim: The objectives of this study are to provide data regarding the prevalence of anti‐cyclic citrullinated peptide (CCP) antibodies in Malaysian rheumatoid arthritis (RA) patients and to correlate the levels of anti‐CCP antibody with the Disease Activity Score (DAS). Method: We studied the prevalence of anti‐CCP antibodies in 51 RA patients attending our clinic and 29 controls. We also looked for correlation between anti‐CCP antibody levels with the DAS and parameters such as duration of disease, rheumatoid factor (RF) and disease‐modifying anti rheumatic drug (DMARD) usage. Results: None of the controls demonstrated anti‐CCP antibodies. Forty‐one out of 51 patients (80.4%) were positive for anti‐CCP antibodies. Sensitivity and specificity were 80.4% and 100% respectively in this study. Anti‐CCP levels correlated significantly with rheumatoid factor, but no correlation was observed with the other parameters. Conclusions: Anti‐CCP antibody is prevalent in Malaysian RA patients at 80.4% and more sensitive than RF in our cohort of established RA patients. Even though the anti‐CCP levels correlated with RF, it did not show correlation with DAS.     

Patterns of cardiovascular risk in rheumatoid arthritis

BACKGROUND: Although it is known that rheumatoid arthritis is associated with an increased risk of cardiovascular disease (CVD), the pattern of this risk is not clear. This study investigated the relative risk of myocardial infarction, stroke and CVD mortality in adults with rheumatoid arthritis compared with adults without rheumatoid arthritis across age groups, sex and prior CVD event status. METHODS: We conducted a cohort study among all residents aged >or=18 years residing in British Columbia between 1999 and 2003. Residents who had visited the doctor at least thrice for rheumatoid arthritis (International Classification of Disease = 714) were considered to have rheumatoid arthritis. A non-rheumatoid arthritis cohort was matched to the rheumatoid arthritis cohort by age, sex and start of follow-up. The primary composite end point was a hospital admission for myocardial infarction, stroke or CVD mortality. RESULTS: 25 385 adults who had at least three diagnoses for rheumatoid arthritis during the study period were identified. During the 5-year study period, 375 patients with rheumatoid arthritis had a hospital admission for myocardial infarction, 363 had a hospitalisation for stroke, 437 died from cardiovascular causes and 1042 had one of these outcomes. The rate ratio for a CVD event in patients with rheumatoid arthritis was 1.6 (95% confidence interval (CI) 1.5 to 1.7), and the rate difference was 5.7 (95% CI 4.9 to 6.4) per 1000 person-years. The rate ratio decreased with age, from 3.3 in patients aged 18-39 years to 1.6 in those aged >or=75 years. However, the rate difference was 1.2 per 1000 person-years in the youngest age group and increased to 19.7 per 1000 person-years in those aged >or=75 years. Among patients with a prior CVD event, the rate ratios and rate differences were not increased in rheumatoid arthritis. CONCLUSIONS: This study confirms that rheumatoid arthritis is a risk factor for CVD events and shows that the rate ratio for CVD events among subjects with rheumatoid arthritis is highest in young adults and those without known prior CVD events. However, in absolute terms, the difference in event rates is highest in older adults.     

Antibodies to RNA polymerase III in systemic sclerosis detected by ELISA

OBJECTIVE: To determine serological and clinical variables associated with anti-RNA polymerase III (RNAP-III) antibodies in patients with systemic sclerosis (SSc) using a new ELISA method. METHODS: Sera from 242 patients with SSc were collected from 14 Canadian clinics. Control sera were from 287 blood donors, and 42 patients with infectious disease, 30 with rheumatoid arthritis (RA), and 30 with systemic lupus erythematosus (SLE). Antibodies to RNAP-III were detected by an ELISA kit and antibodies to other cellular antigens were identified by indirect immunofluorescence (IIF) on HEp-2 cell substrate, line immunoassay, immunoprecipitation of recombinant protein, and addressable laser bead immunoassay (ALBIA). RESULTS: Anti-RNAP-III antibodies were detected in 47/242 (19.4%) SSc sera, 0% RA and SLE sera, 1/287 blood donor sera, and 2/42 infectious disease sera. Diffuse disease (59.5%) was more common than limited disease (36.1%) in the anti-RNAP-III-positive patients (p = 0.006) and there was an association between the presence of anti-RNAP-III and kidney and joint/tendon involvement, but there was no association with a nucleolar IIF pattern, lung involvement, or other clinical indicators. There was a negative association between the presence of anti-RNAP-III antibodies and anticentromere by IIF (p = 0.00004) and anti-Scl-70 by ALBIA (p = 0.0005) and line immunoassay (p = 0.003), suggesting a virtually exclusive presence of these antibodies in SSc. CONCLUSION: Anti-RNAP-III autoantibodies were found in nearly 20% of SSc patients but in less than 1% of controls, thus detection of this antibody is a useful marker to help diagnose SSc. As well, this antibody has prognostic utility, since it is associated with scleroderma renal crisis and the diffuse cutaneous form of SSc.     

Antiferritin antibodies discovered by phage display expression cloning are associated with radiographic damage in rheumatoid arthritis

OBJECTIVE: Several autoantibodies have been described in individuals with rheumatoid arthritis (RA), leading to interest in the use of such antibodies as diagnostic or prognostic markers in RA as well as in their relevance to disease pathology. The objective of this study was to use a phage display expression cloning system to identify novel autoantibody targets in RA. METHODS: We used immunoscreening of a phage-displayed complementary DNA (cDNA) library to isolate a cDNA clone encoding the ferritin heavy chain polypeptide. Antiferritin antibody levels in patients with early and established RA, healthy controls, and disease controls were measured by enzyme-linked immunosorbent assay. Antibody-positive and antibody-negative individuals were compared with respect to disease severity as measured by the modified Larsen score, demographic variables, rheumatoid factor status, and carriage of HLA-DRB1 shared epitope alleles. RESULTS: Antiferritin antibodies were present in 60 (16%) of 366 patients with established RA, 23 (19%) of 118 patients with early RA, 2 (2.7%) of 73 healthy blood donors, 2 (2.1%) of 94 individuals with osteoarthritis, and 2 (2.1%) of 97 patients with systemic lupus erythematosus (P < 0.01, RA patients versus healthy and disease controls). Antiferritin antibodies were more common in men than in women (28.4% versus 12.2%; P < 0.001), and antiferritin levels were associated with the severity of joint damage (P = 0.01). CONCLUSION: Antiferritin antibodies are observed in a subset of patients with RA, are present early in the disease course, and are associated with the severity of radiographic damage. Further studies are required to explore their potential as diagnostic and prognostic markers in RA.     

Impaired humoral immune response against mycobacterial 65-kDa heat shock protein (HSP65) in patients with inflammatory bowel disease

Since only scarce data are available on the immune response against heat shock proteins (HSP) in inflammatory bowel disease (IBD), we have measured with an ELISA method serum levels of IgG, IgA, and IgM antibodies to mycobacterial HSP65 and human HSP60 in 66 patients with Crohn's disease (CD), 42 patients with ulcerative colitis (UC), and 126 age- and gender-matched healthy controls. Serum concentration [median (25th–75th percentiles) of IgG anti-HSP65 antibodies was substantially lower in patients with either CD (P < 0.01) or UC (P < 0.001) than in healthy controls, while no difference was found in the levels of anti-HSP60 antibodies. Low anti-HSP65 antibody levels were measured in patients with active CD and in both active and inactive UC, and only in IBD patients with no extraintestinal manifestations. In conclusion, our present findings indicate that an abnormal immune response to bacterial HSP65 or some epitopes of the protein may contribute to the dysregulation of host defenses against certain intestinal bacteria.     

Obesity is independently associated with impaired quality of life in patients with rheumatoid arthritis

Obesity is a modifiable major cause of morbidity and mortality in the general population, but little is known about the association of obesity and quality of life in patients with rheumatoid arthritis (RA). Thus, we set out a study to test the hypothesis that obesity is independently associated with lower quality of life in patients with RA. Three hundred and fifty nine patients with RA underwent an interview, physical exam, and all clinical charts were reviewed. Based on body mass index (BMI), patients were classified as normal (BMI < 25 kg/m(2)), overweight (BMI = 25-29.9 kg/m(2)), and obese (BMI > or = 30 kg/m(2)). Quality of life was quantified with the Medical Outcomes Study Short Form 36 (SF-36). Data obtained included demographic variables, extra-articular disease, comorbidities, presence of X-ray erosions, rheumatoid factor, and depression. The association between obesity and quality of life was examined with the use of multiple lineal regression models. One hundred and seventy-two patients (47.9%) had normal BMI, 126 (35.1%) were overweight, and 61 patients (17%) were obese. Obese patients had lower quality of life (30.8 +/- 18.1) than overweight patients (43.3 +/- 20.1) and patients with normal weight (43.8 +/- 22.2), P < 0.001. The association between obesity and impaired quality of life was confirmed with a linear regression model (Coef = -12.9, P < 0.001) and remained significant after adjustment for age, sex, disease activity, extra-articular disease, comorbidities, X-ray erosions, presence of rheumatoid factor, depression, education, and disease duration (Coef = -5.3, P = 0.039). In conclusion, obesity is independently associated with the impaired quality of life in patients with rheumatoid arthritis.     

Significance of antikeratin antibodies in rheumatoid arthritis

Antikeratin antibodies (AKA) were found in the sera of 59% (121/204) of patients with rheumatoid arthritis (RA). There was a significantly higher incidence of AKA (73%) in male patients compared with females (53%) and a correlation between AKA positivity and IgM rheumatoid factor was found. Antibody reactivity was positively associated with the presence of nodules, antinuclear antibody, C-reactive protein and disease severity. AKA would appear to have possible prognostic significance in patients with RA.     

Serum levels of anti heat shock protein 70 antibodies in patients with stable and unstable angina pectoris

BACKGROUND: The heat shock protein (HSP) family comprises approximately 24 proteins displaying a high degree of sequence homology between different species. The induction of self-HSP immune reactivity is thought to be involved in the pathogenesis of several diseases. Antibodies to HSP60/65 have been demonstrated in the sera of patients with coronary artery disease. Moreover, the target antigens of the antibodies HSP60 and HSP70 are both expressed in smooth muscle cells and macrophages within atherosclerotic lesions. In this retrospective, case control study, we investigated whether patients with established atherosclerosis, with either stable or unstable angina have high levels of antibodies to HSP70. METHODS AND RESULTS: Patients with stable angina (n = 40) were from the outpatient clinic whereas patients with unstable angina (n = 91) were recruited upon admission and prior to performance of coronary angiography. Control patients (n = 18) were healthy subjects with no evidence of coronary artery disease. Serum levels of anti-HSP70 antibodies were assayed by ELISA. Patients with stable and unstable angina exhibited lower serum levels of antibodies to HSP70 (0.202+/-0.113 and 0.201+/-0.115, respectively) in comparison to control subjects (0.364+/-0.199, P = 0.0001 for both comparisons). Serum levels of antibodies to HSP70 did not differ significantly between patients with stable and unstable angina. No differences in serum levels of antibodies to HSP70 were evident between baseline and follow up in the patients with unstable angina. CONCLUSIONS: Patients with coronary atherosclerosis possess lower levels of anti-HSP70 antibody levels. Further research is required to explore whether higher levels of anti-HSP70 antibodies have a predictive value in coronary atherosclerosis.