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ID PMID Title PublicationDate abstract
15476204 A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides 2004 Oct OBJECTIVE: The main genetic risk factor for rheumatoid arthritis (RA) is the shared epitope (SE) of HLA-DR, while smoking is an important environmental risk factor. We studied a potential gene-environment interaction between SE genes and smoking in the etiology of the 2 major subgroups of RA: rheumatoid factor (RF)-seropositive and RF-seronegative disease. METHODS: A population-based case-control study involving incident cases of RF-seropositive and RF-seronegative RA (858 cases and 1,048 controls) was performed in Sweden. Cases and controls were classified according to their cigarette smoking status and HLA-DRB1 genotypes. The relative risk of developing RA was calculated for different gene/smoking combinations and was compared with the relative risk in never smokers without SE genes. RESULTS: The relative risk of RF-seropositive RA was 2.8 (95% confidence interval [95% CI] 1.6-4.8) in never smokers with SE genes, 2.4 (95% CI 1.3-4.6) in current smokers without SE genes, and 7.5 (95% CI 4.2-13.1) in current smokers with SE genes. Smokers carrying double SE genes displayed a relative risk of RF-seropositive RA of 15.7 (95% CI 7.2-34.2). The interaction between smoking and SE genes was significant, as measured by the attributable proportion due to interaction, which was 0.4 (95% CI 0.2-0.7) for smoking and any SE, and 0.6 (95% CI 0.4-0.9) for smoking and a double SE. Neither smoking nor SE genes nor the combination of these factors increased the risk of developing RF-seronegative RA. CONCLUSION: The disease risk of RF-seropositive RA associated with one of the classic genetic risk factors for immune-mediated diseases (the SE of HLA-DR) is strongly influenced by the presence of an environmental factor (smoking) in the population at risk.
11877617 Arthroscopy of the proximal interphalangeal and metacarpophalangeal joints in rheumatoid h 2002 Mar PURPOSE: To describe our experience with arthroscopy of the proximal interphalangeal (PIP) and metacarpophalangeal (MP) joints and to assess the value of this technique. TYPE OF STUDY: Case series. METHODS: Arthroscopy was performed on 27 PIP joints and 16 MP joints of 21 patients with rheumatoid arthritis (mean age, 47.2 years; range, 26 to 62 years). After arthroscopic examination, 24 joints were treated with joint irrigation only and 19 were treated with arthroscopic synovectomy. All procedures were performed on an outpatient basis. The diameter of the arthroscope was 1.5 mm, and mini-forceps and a mini-shaver system with a 2.5-mm cutter were used for biopsy and synovectomy. We developed new portals for the PIP joints on the dorsal-lateral aspect, more lateral than previously reported portals. RESULTS: The articular cartilage and synovial membrane of the PIP and MP joints were well visualized, and arthroscopy revealed cartilage changes and synovial proliferation. Because the PIP joint space was not wide enough to insert the arthroscope into the palmar cavity, the palmar part of the articular surfaces and the volar synovium could not be inspected. Synovial biopsy of the dorsal joint capsule was easily performed under arthroscopic visualization. Synovectomy of the dorsal joint capsule and both the radial and ulnar recesses was also possible using the 2-portal technique with a mini-shaver system. No intraoperative or postoperative complications were encountered. CONCLUSIONS: Arthroscopy of the PIP and MP joints is useful in assessing articular cartilage and synovium and for synovial biopsy. Arthroscopic synovectomy can be performed safely with the 2-portal technique.
12117675 One year outcome of undifferentiated polyarthritis. 2002 Aug OBJECTIVE: To identify variables that can predict a progressive outcome after one year of follow up in patients presenting with undifferentiated polyarthritis (UPA) at an early arthritis clinic. METHODS: New patients with arthritis in two or more joints of less than three years' duration were categorised at entry as UPA or as rheumatoid arthritis (RA) based on the clinical diagnosis of the rheumatologist. Outcome variables after one year were radiographic damage (Sharp/van der Heijde score) and functional status (Health Assessment Questionnaire: HAQ score). A progressive disease at one year was defined as radiographic progression > or =4, or one year radiographic damage > or =10, or HAQ score > or =1. The baseline variables of patients with UPA with a progressive or mild outcome were compared. RESULTS: 280 patients (70% women; median age 56 years (range 18-90), median duration of symptoms 3.5 months) were included. 203 (72%) patients were clinically diagnosed as having RA and 77 (27%) as having UPA. The group of patients with progressive UPA (n=32 (42%)) had a significantly higher mean age, prevalence of arthritis of the hands, and disease activity (DAS28) at the first visit compared with the patients of the mild UPA group (n=45 (58%)). The RA group had significantly more frequent serum IgM-RF positivity, higher mean disease activity (DAS28) and mean C reactive protein concentration, more frequent symmetric arthritis, and arthritis in more than three joint groups than the progressive UPA group. Six (19%) of the progressive UPA group versus eight (4%) of the RA group did not receive disease modifying antirheumatic drugs during the first year. CONCLUSIONS: After one year of follow up, 32 (42%) of the patients with UPA had a progressive disease. A progressive outcome was associated with older age, higher disease activity, and arthritis of the hands at baseline. To avoid undertreatment of patients with UPA, treatment should be based on severity rather than on diagnosis.
15067519 Immune complex-type glomerulonephritis with unusual giant deposits in a patient with activ 2004 Mar A 61-year-old woman with rheumatoid arthritis (RA) developed small digital ulcers, proteinuria, and hematuria. Serological studies disclosed high titers of antinuclear antibody and rheumatoid factors (RF; IgM-RF and IgG-RF), and an increased level of circulating immune complexes. These findings suggested an active immunological state of RA. A renal biopsy showed periodic acid-Schiff-positive giant deposits in the mesangial area and subepithelial space. Immunofluorescence microscopy revealed strong stainings for IgG, IgA, IgM, Kappa, Lambda, C3, C1q, and fibrinogen in a granular pattern. Electron microscopy showed giant granular deposits (diameter, up to 4.6 micro m) without specific fibrillary structure in the mesangial area and subepithelial space, and partially in the subendothelial space. There were no findings of vasculitis, such as endothelial proliferation or fibrinoid necrosis of small arteries. This is the first report of immune complex-type glomerulonephritis with unusual giant deposits in a patient with RA in an active immunological state.
15027271 Rheumatoid arthritis: hand function, activities of daily living, grip strength and essenti 2003 Nov Persons with rheumatoid arthritis use assistive devices to enable them, in spite of impaired hand dexterity and grip strength, to manage Activities of Daily Living (ADL). The aim of the research was to lay the foundation for a list of essential assistive devices through determining which assistive devices for ADL were most often used and requested, investigating whether there was a correlation between grip strength and the number of assistive devices, duration of disease, degree of difficulty in performing ADL and by investigating whether there was a correlation between difficulty in ADL and number of assistive devices, duration of the disease. STUDY SAMPLE: Fifty five persons, 42 females and 13 males, seen at the Pretoria Academic Hospital's Arthritis Clinic were recruited. MATERIALS AND METHODS: A questionnaire was used to determine the level of difficulty with ADL. Details about assistive devices were recorded. The modified sphygmomanometer was used to measure grip strength. RESULTS: Assistive devices most in use were the tap turner and the dagger knife with built up handle. The highest correlation was found between grip strength and difficulty in ADL and between difficulty in ADL and the number of assistive devices used. It seems therefore that loss of grip strength is the main indicator for assistive devices.
15128195 Sagittal laser optical tomography for imaging of rheumatoid finger joints. 2004 Apr 7 We present a novel optical tomographic imaging system that was designed to determine two-dimensional spatial distribution of optical properties in a sagittal plane through finger joints. The system incorporates a single laser diode and a single silicon photodetector into a scanning device that records spatially resolved light intensities as they are transmitted through a finger. These data are input to a model-based iterative image reconstruction (MOBIIR) scheme, which uses the equation of radiative transfer (ERT) as a forward model for light propagation through tissue. We have used this system to obtain tomographic images of six proximal interphalangeal finger joints from two patients with rheumatoid arthritis. The optical images were compared to clinical symptoms and ultrasound images.
12678429 Autoantigens and immune pathways in rheumatoid arthritis. 2002 Rheumatoid arthritis (RA) is a major systemic autoimmune disease. A plethora of putative autoantigens has been described by the reactivity of antibodies present in the sera of patients. Despite this there is little evidence implicating most of them in its pathogenesis. Autoantigens fall into two major groups: first, those that are associated with the joint, such as collagen type II, human chondrocyte glycoprotein 39, and proteoglycans, for which a pathogenic role is easily understood; and second, those proteins not associated with the joint. Of these there are three groups: (1) highly conserved foreign antigens with human homologues, such as heat shock proteins (HSPs), in which the initiating antigenic stimulus may be through infection; (2) post-translationally altered proteins, such as citrullinated filaggrin, to which autoantibodies show high specificity but low sensitivity for RA and immunoglobulin G; and (3) ubiquitous proteins, such as glucose-6-phosphate isomerase, p205, and HSPs secreted during stress, such as BiP. The mechanisms by which such ubiquitous antigens cause pathology predominantly in the joints are difficult to understand. Autoantibodies, such as rheumatoid factors, that form immune complexes resulting in activation of phagocytic cells or the complement system, may cause joint pathology by deposition in the joints. Such an explanation, however, is not available for all of these autoantigens. It is possible that pathology may be the outcome of disturbed immunoregulation.
16285892 Chemokines and chemokine receptors as novel therapeutic targets in rheumatoid arthritis (R 2004 Oct Chemokines belong to a large family of inflammatory cytokines responsible for migration and accumulation of leukocytes at inflammatory sites. Over the past decade, accumulating evidence indicated a crucial role for chemokines and chemokine receptors in the pathophysiology of rheumatoid arthritis (RA). RA is a chronic autoimmune disease in which the synovial tissue is heavily infiltrated by leukocytes. Chemokines play an important role in the infiltration, localization, retention of infiltrating leukocytes and generation of ectopic germinal centers in the inflamed synovium. Recent evidence also suggests that identification of inhibitors directly targeting chemokines or their receptors may provide a novel therapeutic strategy in RA. Traditional Chinese medicines (TCMs) have a long history in the treatment of inflammatory joint disease. The basis for the clinical benefits of TCM remains largely unclear. Our studies have led to the identification of numerous novel chemokine/chemokine receptor inhibitors present in anti-inflammatory TCMs. All of these inhibitors were previously reported by other researchers to have anti-arthritic effect, which may be attributable, at least in part, to their inhibitory effect on chemokine and/or chemokine receptor. Therefore, identification of agents capable of targeting chemokine/chemokine receptor interactions has suggested a mechanism of action for several TCM components and provided a means of identifying additional anti-RA TCM. Thus, this approach may lead to the discovery of new inhibitors of chemokines or chemokine receptors that can be used to treat diseases associated with inappropriately overactive chemokine mediated inflammatory reactions.
15940559 Effects of shoulder arthroplasty and exercise in patients with rheumatoid arthritis. 2005 Jun The aim of this study was to examine pain and shoulder function in patients with rheumatoid arthritis (RA) before and after shoulder arthroplasty and postoperative exercise. Twenty-four patients (26 shoulders) were consecutively included in a multicentre study. Before surgery, at discharge from hospital and after 3 and 6 months, perceived shoulder function and shoulder pain were assessed by visual analogue scales, activities of daily living by the Modified Health Assessment Questionnaire (M-HAQ) and shoulder range of motion (ROM) by a goniometer. All patients showed considerable pain reduction at discharge from hospital (p<0.001). In those with intact rotator cuff and biceps tendon (n=13) improvements were found after 6 months in active and passive abduction and flexion ROMs (p<0.01) and in M-HAQ (p<0.001). Such improvements were not found in those with torn soft tissue (n=12). Preoperatively, abduction and flexion motor deficits (passive ROM >active ROM) were found for the total group (p=0.001). Less flexion motor deficit was found in the intact soft tissue than in the torn soft tissue group after 3 (p=0.002) and 6 months (p<0.001). No group difference was found with respect to abduction motor deficit. In conclusion, pain relief was obtained by all patients. Improvements in ROMs and activities of daily living were influenced by the state of the soft tissue.
12966593 Increased degradation of tryptophan in blood of patients with rheumatoid arthritis. 2003 Sep OBJECTIVE: Activation of the enzyme indoleamine-(2,3)-dioxygenase (IDO) by interferon (IFN)-g leads to enhanced tryptophan conversion to kynurenine. In consequence of chronic immune activation, tryptophan availability is reduced, leading to inhibition of cell proliferation as protein synthesis is affected. Tryptophan deprivation due to IDO activation could therefore be effective in abrogating processes with high metabolic turnover, thus modulating cellular immune response. METHODS: Concentrations of tryptophan, kynurenine, and neopterin were measured by HPLC in the sera of 38 patients with rheumatoid arthritis (RA). The kynurenine:tryptophan ratios (kyn/trp) were calculated to estimate IDO activity. RESULTS: Tryptophan concentrations were lower in patients with RA (median, interquartile range: 44.95 microM, 40.31-49.95 microM) compared to healthy blood donors (62.62 microM, 57.27-74.61 microM; p < 0.001). Kynurenine in patients (1.86 microM, 1.54-2.31 microM) did not differ from controls (2.06 microM, 1.58-2.65 microM; NS). The kyn/trp ratio was higher in patients (42.39 mM/M, 37.02-48.60 mM/M) than in controls (31.72 mM/M; 27.95-35.03 mM/M; p < 0.001). Kynurenine concentrations (rs = 0.611; p < 0.001) and kyn/trp ratios (rs = 0.621; p < 0.001) correlated with neopterin concentrations, which indicate stimulated cellular immune response in patients with RA. CONCLUSIONS: The data point to a role of immune activation and Th1-type cytokine INF-g to induce elevated tryptophan degradation in patients with RA.
12102477 Need and sequence of large joint replacements in rheumatoid arthritis. A 25-year follow-up 2002 May OBJECTIVE: The aim of the present study was to evaluate the number and sequence of large joint replacements (LJR) performed in long-term rheumatoid arthritis (RA) from an inception cohort of 103 patients with rheumatoid factor (RF)-positive RA followed over 25 years. METHODS: A total of 83 patients attended the 15-year and 68 patients the 20-year follow-up. Patient documents and radiographs were evaluated in the beginning of 2001 and a complementary interview was arranged to assess the number and sequence (timing) of LJRs performed. RESULTS: The cumulative number of LJRs performed for 22 patients (19 women) during the 25 years of follow-up was 41. Seventeen total hip joint replacements (THR) (42% of the total number of 41 LURs) were performed on 13 patients, median time from the diagnosis to the operation being 14 years; 14 total knee replacements (TKR) (34%) on 11 patients (after a median time of 17 years); 3 total shoulder replacements (TSR) (7%) on 3 patients (median time of 18 years); and 7 total elbow replacements (TER) (17%) on 4 patients (median time of 21 years), respectively. Six patients had undergone three or more LJRs during the follow-up period. CONCLUSION: During our 25 years of follow-up, in 27% of RA patients LUR was needed, and 41% of them needed more than one replacement.
12584837 [Study on abnormality and regulation of T-lymphocyte subsets in peripheral blood of rheuma 2002 May OBJECTIVE: To investigate the change of T-lymphocyte subsets in peripheral blood of rheumatoid arthritis (RA) patients and analyze the effects of Fuzheng Qubi Decoction (FZQBD) on T-cell subsets. METHODS: Thirty RA patients were randomly divided into two groups, and treated with FZQBD or western medicine combination therapy respectively for one month, the percentage of peripheral CD3+, CD4+, CD8+ as well as the serum IgG and IgA levels were determined. RESULTS: The percentage of peripheral CD4+, CD4+/CD8+ ratio, IgG and IgA levels increased significantly (P < 0.001) in RA patients before treatment. After 1 month of FZQBD treatment, the CD4+/CD8+ ratio decreased obviously (P < 0.05). CONCLUSION: Abnormal cellular immunity exists in RA patients, FZQBD could adjust the abnormal T-lymphocyte subsets to normalize it.
12079899 Autoantibodies against interleukin 1alpha in rheumatoid arthritis: association with long t 2002 Jul OBJECTIVES: To investigate the possible association of interleukin 1alpha autoantibodies (IL1alpha aAb) with the long term course of joint erosion in patients with rheumatoid arthritis (RA). METHODS: Serum samples from 176 patients with RA included in a prospective study over 30 years were analysed for IL1alpha aAb by binding to human [(125)I]IL1alpha. Erosions of 19 diarthrodial joints were radiographically scored by the Larsen method. RESULTS: The relative risk (RR) of early IL1alpha aAb positive patients developing at least 30% of maximum radiographic joint destruction was significantly lower than for IL1alpha aAb negative patients, RR=0.29 (p=0.04). In rheumatoid factor positive patients RR was only 0.18 (p=0.02). Patients who seroconverted more than two years after the onset of RA showed the most aggressive development of joint erosion, with a relative risk of at least 40% of maximum radiographic joint destruction of 2.56 (p=0.048) CONCLUSIONS: The progression of radiographic joint destruction in patients with RA is associated with, and perhaps modified by, circulating IL1alpha aAb, suggesting that IL1alpha or IL1alpha aAb, or both, have a role in the erosive processes. IL1alpha aAb appear to be of prognostic significance in RA.
12628952 Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. 2003 Mar 11 BACKGROUND: Rheumatoid arthritis may be associated with an increased risk of cardiovascular disease. We compared the incidence rates of myocardial infarction and stroke in subjects with and without rheumatoid arthritis. METHODS AND RESULTS: A prospective cohort study was conducted among the 114 342 women participating in the Nurses' Health Study who were free of cardiovascular disease and rheumatoid arthritis at baseline in 1976. All self-reported cases of rheumatoid arthritis were confirmed by medical record review. Fatal and nonfatal myocardial infarctions and strokes were similarly confirmed. Multivariate pooled logistic regression was used to adjust for potential cardiovascular risk factors. Five hundred twenty-seven incident cases of rheumatoid arthritis and 3622 myocardial infarctions and strokes were confirmed during 2.4 million person-years of follow-up. The adjusted relative risk of myocardial infarction in women with rheumatoid arthritis compared with those without was 2.0 (95% confidence interval [CI], 1.23 to 3.29). For stroke, the adjusted relative risk was 1.48 (95% CI, 0.70 to 3.12). Women who had rheumatoid arthritis for at least 10 years had a risk for myocardial infarction of 3.10 (95% CI, 1.64 to 5.87). CONCLUSION: In this large prospective cohort of women, participants with rheumatoid arthritis had a significantly increased risk of myocardial infarction but not stroke compared with those without rheumatoid arthritis. If these data are confirmed, aggressive coronary heart disease prevention strategies should be tested for persons with rheumatoid arthritis.
12379893 Development of rheumatoid arthritis following autologous peripheral blood stem cell transp 2002 Oct A 51-year-old man with non-Hodgkin's lymphoma (NHL) was treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT). Although he had HLA-DRB1 0405 and a positive rheumatoid factor, he was unlikely to develop rheumatoid arthritis (RA) according to diagnostic criteria. However, the patient developed RA 40 days after transplantation. Our experience suggests that the systemic autoimmune disease, RA, may occur in patients with predisposing factors after autologous PBSCT.
15446527 Seventeen-year survivorship analysis of silastic metacarpophalangeal joint replacement . 2004 Sep We reviewed the records and radiographs of 381 patients with rheumatoid arthritis who had undergone silastic metacarpophalangeal joint replacement during the past 17 years. The number of implants was 1336 in the course of 404 operations. Implant failure was defined as either revision or fracture of the implant as seen on radiography. At 17 years, the survivorship was 63%, although on radiographs two-thirds of the implants were seen to be broken. Factors which improved survival included soft-tissue balancing, crossed intrinsic transfer and realignment of the wrist. Surgery to the thumb and proximal interphalangeal joint had a deleterious effect and the use of grommets did not protect the implant from fracture.
12844099 Clinical relevance of peripheral vascular occlusive disease in patients with rheumatoid ar 2003 Jul INTRODUCTION: Peripheral vascular occlusive disease (PVOD) and rheumatologic disease (RD) are common in older patients. The effect that coexistence of these diseases may have on patient health has not been rigorously investigated. The present study was undertaken in an attempt to characterize patients with PVOD plus RD in terms of inflammatory serologic disorders, medications, and procedures, and their relation to limb salvage. METHODS: Medical records were reviewed retrospectively for all patients with diagnosed coexistent PVOD and non-arteritis RD treated over 15 years at the University of Michigan Hospital. Demographics, operative and medical therapies, and serologic studies were analyzed. Univariate and multivariate analysis and the Kaplan-Meier method were used to assess these variables in relation to limb salvage. RESULTS: Forty-one patients (34 women, 7 men), with mean age of 67 years, were studied. Mean antinuclear antibody titer was 274, C-reactive protein concentration was 3.1 mg/mL, and sedimentation rate was 49. Twenty-nine percent of patients had claudication, 49% had rest pain, and 32% had tissue loss. Mean ankle brachial index was 0.55. Medications included nonsteroidal anti-inflammatory drugs (67% of patients), corticosteroids (54%), and specific immunosuppressive agents (27%). Operative therapy included aortofemoral bypass grafting (n = 4), infrainguinal bypass grafting (n = 14), embolectomy (n = 4), and primary amputation (n = 7). Overall 5-year limb salvage rate was 70% in patients undergoing bypass surgery. Comparison of surgical with nonsurgical patients showed no significant differences in baseline risk factors, serologic disorders, or anatomic location of vascular disease. Multivariate analysis revealed that rest pain and lack of immunosuppression were significantly predictive of need for revascularization or amputation (P <.05). CONCLUSION: Patients with RD should receive treatment on the basis of standard criteria for limb ischemia, in that surgical revascularization outcomes are satisfactory. Immunosuppressive agents may confer a protective effect against progression of PVOD.
15491794 Antigen-based immunointervention in human autoimmune diseases. 2004 Nov Antigen administration can ameliorate autoimmune disease via various mechanisms, including deletion of autoreactive cells, induction of regulatory T cells, and deviation to non-pathogenic or protective responses. All these mechanisms of immunointervention have been successfully used to prevent and sometimes treat experimental models of autoimmune diseases. Based on these results, expectations have been raised for exploiting similar strategies to inhibit pathogenic autoreactive T cells in human autoimmune diseases. Among them, mucosal administration of autoantigen is an attractive mode of immunointervention still awaiting demonstration of clinical efficacy in human autoimmune diseases. A further step in this direction is now provided by the clear-cut immune deviation observed following oral administration of a disease-related peptide to rheumatoid arthritis patients, leading to inhibition of Th1 while enhancing Th2 and possibly Foxp3-positive regulatory T cells.
11954890 Calciphylaxis in a patient with rheumatoid arthritis without renal failure and hyperparath 2002 Feb Calciphylaxis is a rare and life-threatening condition of progressive cutaneous necrosis secondary to small and medium-sized vessel calcification that is seen almost exclusively in patients with end-stage renal disease and hyperparathyroidism. We report a case of calciphylaxis that may very well be due to a long-term steroid use in a rheumatoid arthritis patient who had neither end-stage renal disease nor hyperparathyroidism. We also discuss the possible role of protein S deficiency as a contributing factor.
14872479 Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial me 2004 Feb OBJECTIVE: Autoantibodies have been demonstrated in single serum samples from healthy subjects up to 10 years before they developed rheumatoid arthritis (RA). However, the time course for the development of antibodies before onset of clinical RA is unknown, nor is it known which antibody, or combinations of antibodies, might be most sensitive or specific for predicting future development of the disease. The present study was undertaken to investigate this. METHODS: Patients with RA who had been blood donors before the onset of disease symptoms were enrolled. Frozen serum samples from each donor were retrieved, together with 2 serum samples from controls matched for age, sex, and date of donation. All samples were tested for IgM rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies. RESULTS: Seventy-nine patients with RA (62% female; mean age at onset of symptoms 51 years) were included. A median of 13 samples (range 1-51) per patient were available; the earliest samples had been collected a median of 7.5 years (range 0.1-14.5) before the onset of symptoms. Thirty-nine patients (49%) were positive for IgM-RF and/or anti-CCP on at least one occasion before the development of RA symptoms, a median of 4.5 years (range 0.1-13.8) before symptom onset. Of the 2,138 control samples, 1.1% were positive for IgM-RF, and 0.6% were positive for anti-CCP. CONCLUSION: Approximately half of patients with RA have specific serologic abnormalities several years before the onset of symptoms. A finding of an elevated serum level of IgM-RF or anti-CCP in a healthy individual implies a high risk for the development of RA. We conclude that IgM-RF and anti-CCP testing with appropriately high specificity may assist in the early detection of RA in high-risk populations.