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ID PMID Title PublicationDate abstract
17039310 SAA1 gene polymorphisms and the risk of AA amyloidosis in Japanese patients with rheumatoi 2006 To investigate the precise modality of association between SAA1 gene polymorphisms and the development of AA amyloidosis in patients with rheumatoid arthritis (RA), Japanese patients with RA (n=153), among whom 29 were histologically diagnosed as having amyloidosis, were genotyped for three single nucleotide polymorphisms (SNPs), C-13T, C2995T, and C3010T, in the SAA gene. Pairwise linkage disequilibrium coefficients between each pair of SNPs were calculated and estimated haplotype frequencies were compared between patients with and without amyloidosis. Possible associations between these SNPs and amyloidosis were analyzed by a case-control study and by the Kaplan-Meier method, in which the endpoint was defined as the time of diagnosis of AA amyloidosis. The -13T and 2995C alleles, which were in a tight linkage disequilibrium, were more frequent in the patients with amyloidosis, and the groups with the -13TT and 2995CC genotype had worse survival curves than patients without these genotypes, whereas C3010T was not associated with amyloidosis. Moreover, the haplotype containing -13C and 2995T was found to be protective. Both C-13T and C2995T were associated with the development of amyloidosis. Examining both polymorphisms may be more useful than examining only one of them for estimating the risk of the development of amyloidosis.
15775748 Temperament and satisfaction with health status among persons with rheumatoid arthritis. 2005 Mar PURPOSE: Health-related quality of life is a subjective phenomenon shaped by personal attributes. Research has demonstrated links between temperament and health outcomes. Because temperament is relatively stable, it could function as a moderator of quality of life. This study examined relationships among temperament disposition and satisfaction with health status. DESIGN: The model developed by Sprangers and Schwartz was used to develop a secondary analysis of data collected in a cross-sectional, correlational study with stepwise linear regression analysis. Instruments used were MPQ (dispositions) and AMIS2 (health satisfactions). SETTING: Two rheumatology private practices and 3 rheumatology clinics. SAMPLE: One hundred fifty-three persons diagnosed with rheumatoid arthritis (mean age = 55.4). FINDINGS: Scores reflecting Negative Affectivity (intrapersonal orientation and perception) demonstrated significant positive correlation (r = .26-.58) with all health domain satisfaction scores (P < .001). Negative Affectivity and Positive Affectivity (interpersonal orientation) jointly predicted 8.2%-37.8% of score variance. CONCLUSION: Temperament dispositions are associated with health-related satisfaction. IMPLICATION: Assessment of temperament can facilitate early identification of potential problems in the 3 quality of life domains (meaningfulness, manageability), and comprehensibility, and is useful for selecting or designing tailored interventions.
17133560 Isotype distribution of anti-cyclic citrullinated peptide antibodies in undifferentiated a 2006 Dec OBJECTIVE: The evolution of the rheumatoid arthritis (RA)-specific anti-cyclic citrullinated peptide (anti-CCP) antibody response, as measured by the isotypes of anti-CCP, has not been described. This study was undertaken to determine anti-CCP isotype usage in patients with undifferentiated arthritis (UA), patients with recent-onset RA, and patients with RA of long duration. METHODS: IgA, IgM, and IgG subclasses of anti-CCP were measured by enzyme-linked immunosorbent assay in serum samples that were obtained from IgG anti-CCP antibody-positive patients with UA (n = 110) and IgG anti-CCP antibody-positive patients with RA (n = 152) early after the onset of arthritis. Patients with UA in whom RA developed within 1 year (UA-->RA) were compared with patients with UA in whom RA did not develop within 1 year (UA-->UA). In addition, baseline serum samples obtained from a subset of patients with RA (n = 64) were compared with sera obtained from the same patients a median of 7 years later. RESULTS: IgM anti-CCP was present in early samples from both patients with UA and patients with RA and in followup samples from patients with RA. Several IgG anti-CCP antibody-positive patients who did not have IgM anti-CCP early after disease onset did display IgM anti-CCP later in the course of the arthritis. A diverse pattern of isotype usage was detected in early samples, with a trend toward lower frequencies of all isotypes of anti-CCP in patients with UA compared with patients with RA and in UA-->UA patients compared with UA-->RA patients. Levels of all isotypes except IgG1 had decreased after 7 years. CONCLUSION: These data indicate development of the anti-CCP isotype repertoire into full usage early in the course of arthritis. The sustained presence of IgM anti-CCP indicates ongoing recruitment of new B cells into the anti-CCP response, reflecting a continuous (re)activation of the RA-specific anti-CCP response during the course of anti-CCP-positive arthritis.
17977216 Lymphocytes subsets in osteoarthritis versus rheumatoid arthritis. 2005 It has been suggested that osteoarthritis (OA) is induced by mechanical stress manifested by cartilage destruction with no or minimal involvement of the immune response as compared to that in rheumatoid arthritis (RA). This study is a trial to investigate the hypothesis that the immune response has a critical role in the pathogenesis of OA. This work was performed on 2 groups of patients: the first group included 20 primary OA knee patients and the second group included 18 RA patients as autoimmune controls. Patients of both groups were diagnosed according to the revised criteria of the American college of Rheumatology (ACR). All patients were subjected to complete history taking, clinical examination, degree of severity of OA, disease activity for RA patients and routine laboratory assays. Radiological examinations were done for the wrists, hands and both knees for both RA and OA patients. Flow cytometric assessment of T cell (T helper, T cytotoxic), B cell, Natural killer cells and the CD4/CD8 ratio in the peripheral blood (PB) was carried out for both groups. The results of this study showed no statistical difference between the two studied groups regarding the percentages of the different lymphocyte subsets. These findings reflect the similarity of immune cell profile in both RA and OA patients, and raised the possibility that abnormalities in T cell and its subsets may contribute to the pathogenesis of OA, and predispose to chronic progressive immune response in the synovial membrane (SM) with cartilage destruction. Targeting the cascade that leads to abnormal immune response may open new avenues for treating OA.
17039315 Leflunomide-related acute interstitial pneumonia in two patients with rheumatoid arthritis 2006 We describe two cases of leflunomide-related interstitial pneumonia (IP). A 75-year-old woman with rheumatoid arthritis (RA) developed rapidly progressing IP 45 days after institution of leflunomide. She died of respiratory failure, and an autopsy revealed a mixed pattern of acute and organizing diffuse alveolar damage. A 69-year-old woman with RA also developed acute IP 3 months after institution of leflunomide. Methylprednisolone pulse therapy and cholestyramine ameliorated her IP. The implication of leflunomide in the pathogenesis of IP was suggested.
17038474 Serious infections with antirheumatic therapy: are biologicals worse? 2006 Nov This paper reviews the current evidence for the role of antirheumatic therapy in the development of serious infections in patients with rheumatoid arthritis (RA). Prednisone is clearly associated with increased infectious risk, but no definitive data link methotrexate to infection. Emerging data suggest that biological agents also pose increase infectious risk, particularly when used in combination with corticosteroids or methotrexate. Further research is needed in this important aspect of RA treatment. In the meantime, the author recommends that physicians should remain vigilant for serious infections in their patients with RA and use appropriate vaccines and screening procedures to mitigate their risk.
16758513 Management of infusion reactions to infliximab in patients with rheumatoid arthritis or sp 2006 Jul OBJECTIVE: To suggest recommendations for management of acute infusion reactions induced by infliximab in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: In total, 203 patients were treated with infliximab (120 ml/h). Prevalence of acute infusion reaction was evaluated. To manage these conditions, recommendations were devised according to the type and the severity of clinical manifestations, which were classified beforehand in 2 groups: A (hypertension, pruritus, sudden flush, vomiting, tachycardia or bradycardia, shivers, fever) and B (urticaria, tickling throat, Quincke's edema, dyspnea, and hypotension). Recommendations were based mainly on adjustment of the infusion rate. RESULTS: It was observed that 23/203 patients (11.3%) had acute infusion reactions. Among them and prior to our recommendations, infliximab was completely discontinued in 8/23 patients. After our recommendations were implemented, 15/23 patients presented an acute infusion reaction: 8 and 7 patients with symptoms of Group A and B, respectively. In Group A (8 patients), reducing the infusion rate to 60-80 ml/h led to disappearance of symptoms; the modified treatment was then maintained. In Group B (7 patients), the infusion was immediately stopped and appropriate drugs were administered. Once clinical manifestations were alleviated, the infusion was resumed (60 ml/h). Prior to subsequent infusions (60 ml/h), a premedication was administered. CONCLUSION: Based on these recommendations, infliximab could be maintained with great efficacy on disease activity in every patient with an acute infusion reaction. Our recommendations permit sustained administration of infliximab and allow every patient to benefit from this therapy.
15934268 Tumour necrosis factor alpha and use of infliximab. Safety during pregnancy. 2005 May QUESTION: A 27-year-old patient of mine with rheumatoid arthritis has been treated with infliximab for the last 5 years. She is planning her first pregnancy. How should I advise her regarding use of infliximab during pregnancy, bearing in mind that infliximab substantially improved her medical condition? ANSWER: Infliximab (Remicade) has not been tested in pregnant animals because it does not interact with non-human tumour necrosis factor (TNF) alpha. Several case reports describing women who used infliximab during pregnancy do not suggest a strong association with adverse pregnancy outcomes. More studies are required to determine infliximab's safety during pregnancy.
16696871 Prevalence of amyloid deposition in long standing rheumatoid arthritis in Iranian patients 2006 May 15 BACKGROUND: The study was aimed at determining the prevalence of secondary amyloidosis in a group of Iranian patients with Rheumatoid Arthritis (RA), and the assessment of its correlation with the clinical and laboratory findings and data. METHOD: A total number of 220 patients (167 female and 53 male) with a minimum five-year history of RA were selected. Congo red staining method was used for staining the specimens obtained by abdominal subcutaneous fat biopsy (ASFB) method. All of the specimens were examined for apple-green birefringence under polarized light microscope. Clinical and laboratory characteristics of the patients were assessed. Chi-square test and unpaired student's t-test were run for intergroup comparisons. RESULTS: Amyloid deposition test yielded positive results in 15 out of the 220 cases (6.8%) examined by the ASFB technique. Thirteen patients were found to have minimal amyloid deposits. Of all the clinically significant cases, 8 (53%) presented with proteinuria, and 7 cases (46.6%) had severe constipation. CONCLUSION: The prevalence of fat amyloid deposits in Iranian patients with RA is low. In up to half of the study group the deposits were subclinical. Follow up studies are required to determine whether this subclinical amyloidosis can develop into full-blown clinically significant amyloidosis.
16953396 Accelerated atherosclerosis in pre-menopausal female patients with rheumatoid arthritis. 2006 Dec Increased mortality due to cardiovascular disease in rheumatoid arthritis (RA) patients was reported. Using B-mode ultrasonography we compared intima-media thickness (IMT) and plaque occurrence (indicators of asymptomatic atherosclerosis) in the carotid arteries in 70 pre-menopausal, female RA patients and 40 controls. Correlations with different risk factors were evaluated. The IMT values were higher in RA patients (0.59 mm vs. 0.47 mm, P < 0.0001) and they had more plaques (P = 0.023). In RA patients higher levels of sensitive CRP (P < 0.0001), ICAM (P < 0.0001), VCAM (P < 0.0001), IL-2 (P < 0.001), IL-6 (P = 0.009) and TNF-alfa (P < 0.01) were found. A correlation between IMT and triglycerides (P = 0.018) and a negative correlation between IMT and HDL cholesterol (P = 0.037) were found. With multiple regression analysis the association between IMT and sensitive CRP (P = 0.027) and presence of plaques and apolipoprotein B (P = 0.028) was established. The results indicate that even pre-menopausal, female RA patients had accelerated atherosclerosis. Chronic systemic inflammation may play an important role in atherogenesis.
16847371 Examination of IgM rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide antibo 2006 We have studied the serology of 6 patients with palindromic rheumatism. None of the patients fulfilled the classification criteria for rheumatoid arthritis at the entry; however, 4 out of the 6 patients were seropositive for IgM rheumatoid factor (IgM-RF) at entry. Sequential serological study was performed in 4 patients; IgM-RF changed from seronegative to seropositive in one patient, and the titer increased in another patient. Anti-cyclic citrullinated peptide antibody (anti-CCP Ab) at the entry was detected in only one of the 6 patients; that patient later developed RA. Although follow-up is necessary, the present study may suggest the importance of serological examination, especially anti-CCP Ab, in patients with palindromic rheumatism.
16520462 Prospective study of survival outcomes in Non-Hodgkin's lymphoma patients with rheumatoid 2006 Apr 1 PURPOSE: Although preliminary studies suggest that non-Hodgkin's lymphoma (NHL) complicating rheumatoid arthritis (RA) may be a clinically distinct entity compared with that occurring in the general population, studies examining the impact of antecedent RA on survival are limited. In this prospective study, we examined the association of RA with survival in patients with NHL. PATIENTS AND METHODS: Using two large lymphoma registries, we identified patients with evidence of RA preceding NHL. Survival in RA patients was compared with that of controls using proportional hazards regression, adjusting for the effects of age, sex, lymphoma diagnosis-to-treatment lag time, calendar year, International Prognostic Index score, and NHL grade. RESULTS: The frequency of NHL subtypes was similar in RA patients (n = 65) and controls (n = 1,530). Compared with controls, RA patients with NHL had similar overall survival (hazard ratio [HR] = 0.95; 95% CI, 0.70 to 1.30) but were at lower risk of lymphoma progression or relapse (HR = 0.41; 95% CI, 0.25 to 0.68) or death related to lymphoma or its treatment (HR = 0.60; 95% CI, 0.37 to 0.98), but were more than twice as likely to die from causes unrelated to lymphoma (HR = 2.16; 95% CI, 1.33 to 3.50). CONCLUSION: RA is associated with improved NHL-related outcomes, including a 40% reduced risk of death occurring as a result of lymphoma or its treatment and approximately a 60% lower risk of lymphoma relapse or progression compared with non-RA controls. However, the survival advantage gained in RA from the acquisition of lymphomas with favorable prognoses is negated through an increased mortality from other comorbid conditions.
15996058 Does age bias the aggressive treatment of elderly patients with rheumatoid arthritis? 2005 Jul OBJECTIVE: Age bias has been reported to result in undertreatment of elderly patients with various medical conditions. We investigated whether a similar bias exists in the treatment of elderly patients with rheumatoid arthritis (ELDRA) compared to matched younger controls (YRA). METHODS: We performed an analysis of our RA clinical research registry to determine whether any differences exist between ELDRA and YRA patients with respect to use of combination disease modifying antirheumatic drugs (DMARD), biologic agents, corticosteroids, and nonsteroidal antiinflammatory drugs (NSAID). We also determined whether any difference in clinical status could be identified. RESULTS: Forty-nine female ELDRA subjects (age > 70 yrs) with insurance were matched for sex, insurance status, and duration of disease to YRA subjects (< 60 yrs). No statistically significant difference was noted in number of DMARD currently in use (1.24 +/- 0.78 vs 1.24 +/- 0.69, p = 1.00), or number of patients using biologic agents (25 vs 30; p = 0.31), corticosteroids (16 vs 11; p = 0.26), or NSAID (26 vs 36; p = 0.06). ELDRA and YRA patients also reported similar pain (judged using a visual analog scale, VAS; 3.5 +/- 2.6 cm vs 3.4 +/- 2.2 cm), fatigue (VAS 3.2 +/- 2.7 cm vs 3.9 +/- 2.9 cm), global assessment (VAS 2.8 +/- 2.2 cm vs 3.5 +/- 2.6 cm), and Health Assessment Questionnaire disability scores (0.82 +/- 0.5 vs 0.73 +/- 0.5). CONCLUSION: In this cohort of elderly patients with RA, we detected no bias in the use of RA treatment compared with younger controls. Clinical RA measures also showed that these elderly patients with RA were faring at least as well as the younger controls; they were not relatively undertreated.
16137614 Immunoglobulin G from anti-glucose-6-phosphate isomerase antibodies positive patient with 2005 Sep Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) solely induce arthritis in mice. High titers of anti-GPI Abs are found in some patients with rheumatoid arthritis (RA), but their pathogenic role remains elusive. The aim of this study was to evaluate the pathogenic role of anti-GPI Abs in cynomolgus monkeys. IgG fractions were separated from sera of anti-GPI Abs-positive RA patients and healthy subjects and directly injected into the metacarpophalangeal joints of 4 cynomolgus monkeys. At day 16, the joints were harvested and examined histologically and immunohistochemically. The expression of C5a receptor (C5aR) molecule in the synovium was quantified by real-time PCR using cDNA from monkey joints. In monkey joints, IgG including anti-GPI Abs resulted in recruitment of granulocytes and mononuclear cells, strong deposition of human IgG on the articular surface, and overexpression of C5aR, but no joint swelling. No infiltrated cells or IgG deposition were observed in monkeys injected with IgGs from healthy subjects. Our results suggest that IgG fraction from RA patients including anti-GPI Abs may play a crucial role in the generation of synovitis in monkeys, although the pathogenesis of anti-GPI Abs in RA patients is still uncertain.
17009231 Changes in Health Assessment Questionnaire disability scores over five years in patients w 2006 Oct OBJECTIVE: To analyze longitudinal data over 5 years for changes in Health Assessment Questionnaire (HAQ) scores in patients with rheumatoid arthritis (RA) and age- and sex-matched controls from the general population. METHODS: In 2000 and 2005, identical self-report questionnaires were mailed to a cohort of patients with RA and control cohort from the community. The questionnaire included the HAQ, which was used to assess functional status. Changes in HAQ scores over 5 years were analyzed. RESULTS: In 2000, 73% of 1,495 patients with RA and 77% of 2,000 general population controls responded to the questionnaire. In 2005, 84% of 2,022 patients with RA and 77% of 1,817 controls responded. A total of 863 patients with RA and 1,176 community controls responded in both 2000 and 2005 and were included in the analyses. Mean baseline HAQ scores were significantly higher in patients with RA than in controls (0.71 versus 0.17; P < 0.001). Over 5 years, the HAQ scores increased by 0.01 units per year in both the RA cohort and the community population; in both cohorts, the net change was primarily attributable to individuals over age 70 years. Changes in HAQ scores were similar in patients and controls who had low HAQ scores at baseline. Female patients with baseline HAQ scores of >or=0.5 had less potential for improvement than did controls. Among subjects in both groups who had HAQ scores >2, death was a common outcome over the next 5 years. CONCLUSION: Currently, progression of functional disability among patients with RA and among persons in the general population is largely explained by the aging process. Our results showing stable function scores over 5 years in most patients with RA who are younger than age 70 years provide further evidence of improved status of RA patients today compared with the major declines observed in previous decades.
16320332 Digital X-ray radiogrammetry combined with semiautomated analysis of joint space widths as 2005 Dec OBJECTIVE: To evaluate digital x-ray radiogrammetry (DXR) and the Radiogrammetry Kit program as new diagnostic tools for quantifying disease-related periarticular osteoporosis and for measuring joint space narrowing according to the severity and duration of rheumatoid arthritis (RA). METHODS: Using DXR, we performed computerized calculations of bone mineral density (BMD) and the metacarpal index (MCI) in 258 patients with active RA. Using the Radiogrammetry Kit program, we also performed semiautomated measurements of joint space width (JSW) at the second through the fifth metacarpophalangeal (MCP) joints in these patients. RESULTS: All correlations between the different parameters of both techniques (BMD and the MCI as measured by DXR and MCP JSW as measured by the Radiogrammetry Kit) were significant (0.36 < or = R < or = 0.63; P < 0.01). As expected, a significant negative association was shown between the different MCP JSW results and the results of all scoring methods (-0.67 < or = R < or = -0.29). The BMD and the MCI measured by DXR both decreased significantly between Steinbrocker stage I and stage IV (by 32.7% and 36.6%, respectively; both P < 0.01). Reductions in the overall (mean) MCP JSW varied from 35.3% (Larsen score) to 52.9% (Steinbrocker stage). Over a period of 6 years, we observed relative decreases in BMD and the MCI as measured by DXR (32.1% and 33.3%, respectively), as well as in the overall (mean) MCP JSW (23.5%), and these were pronounced in early RA (duration <1 year). In addition, excellent reproducibility of DXR and Radiogrammetry Kit parameters was verified (coefficients of variation <1%). CONCLUSION: DXR with the integrated Radiogrammetry Kit program could be a promising, widely available diagnostic tool for supplementing the different RA scoring methods with quantitative data, thus allowing an earlier and improved diagnosis of RA and more precision in determining disease progression.
15905576 Cell-based immunotherapy with suppressor CD8+ T cells in rheumatoid arthritis. 2005 Jun 1 The chronic persistence of rheumatoid synovitis, an inflammation driven by activated T cells, macrophages, and fibroblasts causing irreversible joint damage, suggests a failure in physiologic mechanisms that down-regulate and terminate chronic immune responses. In vitro CD8(+)CD28(-)CD56(+) T cells tolerize APCs, prevent the priming of naive CD4(+) T cells, and suppress memory CD4(+) T cell responses. Therefore, we generated CD8(+)CD28(-)CD56(+) T cell clones from synovial tissues, expanded them in vitro, and adoptively transferred them into NOD-SCID mice engrafted with synovial tissues from patients with rheumatoid arthritis. Adoptively transferred CD8(+)CD28(-)CD56(+) T cells displayed strong anti-inflammatory activity. They inhibited production of IFN-gamma, TNF-alpha, and chemokines in autologous and HLA class I-matched heterologous synovitis. Down-regulation of costimulatory ligands CD80 and CD86 on synovial fibroblasts was identified as one mechanism of immunosuppression. We propose that rheumatoid synovitis can be suppressed by cell-based immunotherapy with immunoregulatory CD8(+) T cells.
16622722 Pneumocystis jiroveci pneumonia associated with low-dose methotrexate treatment for rheuma 2006 Low-dose methotrexate (MTX) therapy is widely used for rheumatoid arthritis (RA) because of its favorable efficacy and toxicity profile. Although Pneumocystis jiroveci pneumonia (PCP) is most often seen in severely immunosuppressed patients, PCP complicating low-dose MTX therapy for RA has been reported to sometimes occur. We herein report two cases of patients who developed PCP during treatment with low-dose MTX, and discuss the importance of prophylaxis for this opportunistic infection.
16194737 Total shoulder arthroplasty: long-term survivorship, functional outcome, and quality of li 2005 Sep This study examines long-term outcomes of total shoulder arthroplasty (TSA) via survivorship analysis, patient questionnaires, and minimum 10-year physical examinations. The study group consisted of 320 consecutive TSAs performed in 267 patients between 1974 and 1988. Diagnoses included rheumatoid arthritis (69%), osteoarthritis (22%), and juvenile rheumatoid arthritis (4.7%). Minimum 10-year physical examination follow-up was obtained on a subset of 72 TSAs at a mean (+/- SD) of 14.0 +/- 2.7 years. A Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire was obtained from 80 patients with 103 TSAs at a mean of 15.4 +/- 3.4 years after the index procedure (range, 10.4-23.2 years). Kaplan-Meier survivorship rates with revision as the endpoint at 5, 10, 15, and 20 years were 98%, 93%, 88%, and 85%, respectively. Of the shoulders, 22 (6.9%) required a revision, most commonly for loosening of one or both components (15 shoulders). Dislocation occurred earlier than other causes of revision or complication (P < .05, analysis of variance). Minimum 10-year physical examination follow-up revealed lasting, significant improvements in range of motion and strength. The patients' subjective assessments of TSA were favorable in that 92% felt that their shoulder was "much better" or "better" after TSA. The mean DASH score was 49 +/- 25; no significant differences were found among diagnoses. Long-term analysis of the Neer-type TSA revealed survivorship rates comparable to other joint replacements. The significant improvements in relief of pain, shoulder range of motion, and strength are associated with a high degree of patient satisfaction.
15674368 The PTPN22 R620W polymorphism associates with RF positive rheumatoid arthritis in a dose-d 2005 Mar We have recently described the association between rheumatoid arthritis and a coding single-nucleotide polymorphism in the intracellular protein tyrosine phosphatase, PTPN22. The disease-associated polymorphism, 1858 C/T (rs2476601), encodes an amino-acid change (R620W) in one of four SH3 domain binding sites in the PTPN22 molecule. We have now extended our initial studies to address three questions: (1) Is the association with rheumatoid arthritis limited to rheumatoid factor (RF) positive disease? (2) Does homozygosity for PTPN22 R620W substantially increase disease susceptibility? (3) Is there an interaction between PTPN22 and the rheumatoid arthritis (RA)-associated HLA-DRB1 shared epitope alleles? A total of 1413 Caucasian rheumatoid arthritis patients and 1401 Caucasian controls were genotyped. The results support the view that PTPN22 was strongly and preferentially associated with RF positive disease (OR=1.75, 95% CI 1.46-2.10, P=1.3 x 10(-9)). The PTPN22 risk allele was not significantly associated with RF negative disease (OR=1.19, 95% CI 0.92-1.53, P=0.18), although a very weak association cannot be completely excluded. There was a strong dose effect on disease risk; two copies of the PTPN22 R620W allele more than doubles the risk for RF positive RA (OR=4.57, 95% CI 2.35-8.89). There was no evidence of a genetic association between PTPN22 and HLA susceptibility alleles.