Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
11402401 Posterior cruciate-sacrificing versus posterior cruciate-substituting total knee arthropla 2001 Jun Since the introduction of the Total Condylar Prosthesis (TCP) in 1974, concomitant improvements in surgical technique and prosthetic design have occurred. The individual effects of each of these variables have not been investigated, however. This study evaluates 2 different knee designs using the same operative technique by a single surgeon. All primary total knee arthroplasties performed between 1986 and 1989 were entered into a database of 2 cohorts, TCP and Press Fit Condylar (PFC) knees, matched for age, gender, body weight, and diagnosis. Follow-up data within 12 months of each other were used, evaluating patients clinically and using a self-administered questionnaire. In each cohort, 74 knees were matched by these criteria. Follow-up time was 4.04 and 4.45 years for the TCP and PFC cohorts. Range of motion averaged 107 degrees and 112 degrees for the TCP and PFC cohorts. This difference was statistically significant. Total knee score and functional score improved significantly. Anterior knee pain was present in 9 TCP and 3 PFC knees. Lateral release was performed in 30 TCP and 18 PFC knees. The PFC showed an advantage in ROM, stair function, anterior knee pain, and use of lateral release. Both designs showed comparable pain relief and walking ability.
10460189 The value of synovial fluid analysis in the assessment of knee joint destruction in arthri 1999 Sep OBJECTIVES: To assess the predictive significance of synovial fluid (SF) analysis for progressive radiological knee joint destruction in arthritis. METHODS: Altogether 55 patients with arthritis and knee joint effusion were included in the study. The diagnosis was rheumatoid arthritis (RA) for 44 of them, chronic seronegative spondylarthropathy for seven and juvenile rheumatoid arthritis for four. The mean age of the patients was 51.8 (SD 14.9, range 19-82) years, and the mean duration of disease 10.9 (SD 9.2, range 0.5-37) years. In addition to the routine laboratory tests, different markers of collagen synthesis and breakdown in serum and SF were assessed. The radiological grade of the knee joint was assessed by Larsen's method at the baseline and after a three year follow up. RESULTS: During the follow up, Larsen's grade deteriorated in 22 (40%) patients. These patients had a significantly higher median level of cross linked carboxyterminal telopeptide of type I collagen (ICTP) in SF at entry than those who had a stable index (p = 0.035). Serum ICTP did not have any predictive value for a specific joint. The median levels of total SF leucocytes (p = 0.012) and the subgroup of polymorphonuclear leucocytes (p = 0.018) were higher in the patients with a stable Larsen's index. However, the relation of SF leucocyte level to radiological progression could not be confirmed in the RA group. CONCLUSION: It is concluded that SF analysis may help in the identification of patients with inflammatory arthritis who are at risk for progressive destruction in a particular joint. A high total SF leucocyte level is not necessarily associated with a poor prognosis. Instead, a high SF ICTP level seems to reflect accelerated bone degradation.
9562516 Pro- and anti-inflammatory cytokines in rheumatoid arthritis. 1997 Dec Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the accumulation of inflammatory cells into the synovium and the destruction of joints. Cytokines are important regulators of the synovial inflammation. Some cytokines, such as tumour necrosis factor (TNF)-alpha and interleukin (IL)-1, function by promoting inflammatory responses and by inducing cartilage degradation. Other cytokines, such as IL-4, IL-10 and IL-13, function mainly as anti-inflammatory molecules. Although anti-inflammatory cytokines are present in rheumatoid joints, in progressive RA their levels obviously are too low to neutralize the deleterious effects of proinflammatory cytokines. Inhibiting the action of proinflammatory cytokines by using specific cytokine inhibitors or anti-inflammatory cytokines is the basis for new therapies currently tested in patients with RA. Promising results on the use of neutralizing anti-TNF-alpha monoclonal antibodies in the treatment of RA have been reported. The results from a trial using recombinant IL-10 in the treatment of patients with RA are available in the near future and will be important in determining the therapeutic potential of this cytokine.
15359510 Intraarticular rheumatoid nodule detection in the knee joint using ultrasonography. 2000 Rheumatoid nodules represent a classic diagnostic sign of rheumatoid arthritis. They can be found in 20-25% of patients and are localized to the extensor surface of the proximal ulna and other friction areas such as the back of the head, the sacrum, the digits and the Achilles tendon. They can also develop in some internal organs such as the lungs, kidneys and the heart. Rheumatoid nodules are a characteristic extra-articular feature of RA. Intraarticular rheumatoid nodules are rare and their detection is a diagnostic challenge. There are few reports in the medical literature on their ultrasonographic detection. We report our results from a retrospective study on 9 patients (5 with gait problems and 4 - asymptomatic) with intraarticular rheumatoid nodules in the knee joint. Ultrasonography was most important in their detection. The diagnosis was confirmed histologically in two of our patients following surgical removal of the nodules.
11066188 Evaluating patients with arthritis of recent onset: studies in pathogenesis and prognosis. 2000 Nov 8 Inflammatory synovitis of recent onset poses a diagnostic and prognostic challenge to primary care physicians and rheumatologists. A lack of understanding of the underlying etiologic and pathogenic processes limits the ability to distinguish forms of arthritis that follow a benign, self-limiting course from forms that proceed to an aggressive, erosive disease requiring intensive immunosuppressive therapy. It is estimated that between 30% and 40% of patients presenting with early synovitis have disease that remains unclassified. Using data from a cohort of patients with early synovitis and reviewing current literature, we discuss investigational approaches toward a new classification of patients with early synovitis. Although a lack of understanding of this heterogeneous clinical syndrome has led clinicians to take a largely empirical approach to treatment thus far, the evolving awareness of disease predisposition at a genetic level and the expanding ability to specifically manipulate biological pathways may ultimately change the approach to this clinical problem. JAMA. 2000;284:2368-2373.
10958861 Immunochemical detection of imidazolone in uremia and rheumatoid arthritis. 2000 Oct The advanced glycation end-product imidazolone is formed by reaction of arginine with 3-deoxyglucosone (3-DG), a reactive intermediate of the Maillard reaction, whose formation is non-oxidative. Using an antibody specific to this 3-DG-derived AGE, we demonstrated the presence of imidazolone-modified proteins in vivo in the urine and dialysate of patients with chronic renal failure, in the synovial fluid of patients with rheumatoid arthritis, as well as in vitro in human serum and human serum albumin incubated with glucose. Furthermore, we could show that in uremic patients the dimeric form of beta(2)-microglobulin is more susceptible to imidazolone modification than the monomeric one. Thus, the immunochemical detection of imidazolone may be a good marker for 3-DG-derived AGE modification in vivo and in vitro permitting a differentiation between the oxidative and the non-oxidative pathway of AGE generation.
11033917 One-stage bilateral total hip arthroplasty a simultaneous procedure in 79 patients. 2000 Jun The authors retrospectively studied 79 patients who had undergone simultaneous bilateral total hip arthroplasty during the period 1982 to 1994. Forty one patients were examined clinically and radiographically at least 5 years postsurgery. The procedure was associated with few early postoperative complications and so far excellent results at 7.5 years with regard to patient satisfaction, Hip Functional Index and survival of the prostheses. It is concluded, that in selected patients with bilateral hip disease necessitating bilateral hip replacement, the bilateral operation may be advantageously carried out in one session.
10589368 TNF alpha and IL-1 beta are separate targets in chronic arthritis. 1999 Nov Chronic arthritis is characterized by persistent joint inflammation and concomitant joint destruction. Using murine arthritis models and neutralizing antibodies as well as cytokine-specific knockout conditions, it was found that tumor necrosis factor alpha (TNF alpha) is important in joint swelling, whereas a direct role in tissue destruction is unlikely. Interleukin-1 (IL-1) is not a dominant cytokine in early joint swelling, but has a pivotal role in sustained cell infiltration and erosive cartilage damage. TNF alpha-independent IL-1 production is a prominent feature in murine arthritis models, implying that IL-1 as well as TNF alpha are appropriate targets for therapy. These observations provide evidence for the potential uncoupling of joint inflammation and erosive changes and underline the need for TNF alpha/IL-1 directed combination-therapy approaches.
10384135 Involvement of thioredoxin in rheumatoid arthritis: its costimulatory roles in the TNF-alp 1999 Jul 1 Thioredoxin (TRX) is a cellular reducing catalyst induced by oxidative stress and is involved in the redox regulation of transcription factors such as NF-kappaB. We found that the serum TRX concentration was elevated in patients with rheumatoid arthritis (RA) as compared with values from healthy individuals and patients with osteoarthritis (33.6 +/- 35.1 vs 11.8 +/- 6.6 ng/ml, p < 0.01). Moreover, the TRX concentration in the synovial fluid (SF) was much more elevated in RA patients than in osteoarthritis patients (103.4 +/- 53.3 vs 24.6 +/- 17.4 ng/ml, p < 0.001). Multiple regression analysis revealed that the serum C-reactive protein value was better correlated with the linear combination of SF TNF-alpha and SF TRX values than with SF TNF-alpha alone, suggesting that TRX might play a subsidiary role in the rheumatoid inflammation. We thus examined the effect of TRX on the TNF-alpha-induced IL-6 and IL-8 production using rheumatoid synovial fibroblast cultures. The extents of IL-6 and IL-8 production in response to TNF-alpha were greatly augmented by TRX as compared with TNF-alpha alone. TRX alone did not have such effects. We also found that TRX appeared to accelerate the nuclear translocation of NF-kappaB, a major transcriptional regulator for production of IL-6 and IL-8 on stimulation with TNF-alpha. Consistent with these findings, the IkappaBalpha phosphorylation at Ser32 and its subsequent degradation in response to TNF-alpha was facilitated by TRX. These findings indicate that the elevated TRX concentration in SF of RA patients might be involved in the aggravation of rheumatoid inflammation by augmenting the NF-kappaB activation pathway.
9541594 Polyreactive antigen-binding B cells are the predominant cell type in the newborn B cell r 1998 Mar Polyreactive antibodies bind to a variety of different self and non-self antigens. The B cells that make these antibodies express the polyreactive lg receptor on their surface. To determine the frequency of polyreactive antigen-binding B cells in peripheral blood, we incubated two different antigens, one (insulin) labeled with fluorescein isothiocyanate and the other (beta-galactosidase) with phycoerythrin, with peripheral B cells. The percentage of cells that bound these antigens was determined with the fluorescence-activated cells sorter. Approximately 21% of adult B cells bound insulin, 28% bound beta-galactosidase, and 11% bound both antigens. In contrast to B cells in the adult repertoire, 49% of B cells in cord blood bound insulin, 54% bound beta-galactosidase, and 33% bound both antigens. The properties of polyreactive antigen-binding B cells in adult and cord blood were similar, except for the fact that almost all the polyreactive antigen-binding B cells in cord blood were CD5 positive (93%), whereas only 40% of the polyreactive antigen-binding B cells in adult peripheral blood were CD5 positive, indicating that the CD5 marker is not directly linked to polyreactivity. The percentage of polyreactive antigen-binding B cells in patients with Sjögren's syndrome, systemic lupus erythematosus and rheumatoid arthritis was equal to or slightly below that found in the normal adult B cell repertoire. It is concluded that polyreactive antigen-binding B cells are a major constituent of the normal adult B cell repertoire and are the predominant cell type in the newborn B cell repertoire.
9689647 Florid reactive follicular hyperplasia in elderly patients. A clinicopathological study of 1998 Florid reactive follicular hyperplasia (FRFH) of the enlarged lymph node in elderly patients requiring biopsy is a relatively uncommon phenomenon as compared with younger age groups. We experienced 23 patients, aged 60 years or more, from whom the biopsied lymph node specimens histologically showed inappropriate FRFH for their age, in the period between 1982 and 1996. These cases were morphologically subdivided into three groups, FRFH with interfollicular plasmacytosis, that with progressive transformation of germinal center, and FRFH without additional specific findings. FRFH with interfollicular plasmacytosis were observed in 11 cases, all of whom were accompanied with several immunological abnormalities (six with rheumatoid arthritis, three with multicentric Castleman's disease and one each with myoepithelial sialoadenitis and autoimmune hemolytic anemia). Three men with uncertain etiology exhibited an unusual histology of progressive transformed germinal centers which were clinically characterized by a bulky neck mass. Among the nine cases with nonspecific FRFH, only four had a specific etiology (one each with adult onset Still's disease, chronic sinusitis, Epstein-Barr virus infection and infectious lateral cervical cyst), while the other five with unknown etiology showed abnormal laboratory findings suggestive of an abnormal humoral immune response, i.e. hypergammaglobulinemia and seropositivities for some autoantibodies. None of our patients developed malignant lymphoma during the follow-up period. Of note, 16 (70%) of the 23 cases were found to be associated with various types of imbalances of the immune system, some of which appeared to be currently ill-defined as clinicopathological entities that were simply categorized as autoimmune disease.
10565356 Catabolic proinflammatory cytokines. 1998 May Catabolic proinflammatory cytokines play a key role in mediating biochemical changes associated with many pathophysiological states. The present review emphasizes the role of this type of cytokine in inflammation and cachexia. Additionally, it reviews the role of one of these mediators in the induction of insulin resistance by dealing with some of the most recent publications on this topic.
10587548 Reading radiographs in chronological order, in pairs or as single films has important impl 1999 Dec OBJECTIVE: To determine the influence of reading series of films in chronological order, in pairs with unknown time sequence, or as single films, on precision and sensitivity to change. METHODS: Two studies were performed with 10 and 12 patients fulfilling the American College of Rheumatology criteria. In Study 1, two sets of films with a 1 yr interval were scored in chronological order, in pairs, and as single films. In Study 2, four sets of films, with a 1 yr interval each, were scored in chronological order, as single films and as single-pair (right and left together). All films were scored with the Sharp/van der Heijde method by two independent observers. Data were analysed with a repeated measures ANOVA using a full mixed effects model. Two generalizability (G) coefficients were constructed for reliability and for change. RESULTS: Study 1: the interobserver reliability was similar for the three methods (G(reliability) chronological 0.94, paired 0.88, single 0.93); progression was a mean increase (averaged over patients, observers and methods) from 26 to 37 (P=0.046). The sensitivity for change was greater for the chronological than for the paired and single scoring (G(change) 0.39, 0.22 and 0.24, respectively). Study 2: the interobserver reliability was 0.86 for chronological, 0.76 for single-pair and 0.91 for single readings. Significantly more progression was measured with the chronological compared with the single-paired and single methods (15.9 vs 8.5 and 8.3; P=0.0001). A constant progression was suggested by chronological reading, in contrast to a stabilization in the other two methods after 1 yr. CONCLUSION: Reading films in chronological order is most sensitive to change in a time period up to 3 yr follow-up; this was already present after 1 yr, but even more pronounced with longer follow-up.
11758251 [Expression of CCR5 and its ligand in joint fluid and synovium of patients with rheumatoid 2001 Sep 10 OBJECTIVE: To investigate the expression and distribution of C-C chemokine recepter 5 (CCR5) and its ligand in peripheral blood, synovium, and synovial fluid so as to study the mechanism of selective accumulation of Th1 cells in rheumatoid joints. METHODS: Synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) were isolated from 15 patients with active rheumatoid arthritis (RA). The expressions of intracellular cytokines, CCR5 and CXCR3 on cytomembraine of SFMCs and PBMCs, and MIP-1 immunofluorescence labelling, and flow cytometry. RESULTS: (1) The selective pattern of intracellular cytokines in SFMCs was drifted towards Th1 subset. (2) The expression rate of CCR5 was 52% Y 8%, the expression rate of CXCR3 was 61% Y 12% in synovial fluid, significantly higher than those of PBMCs. (3) In RA tissues, most of the infiltrating T cells (especially CD4+ T cells), monocyres/microphages, and B cells expressed macrophage inflammatory protein, ligand of CCR5. CONCLUSION: Infiltrating T cells (especially CD4+ T((MIP)-1 cells), monocyres/microphages, and B cells in the synovium of inflammatory, RANTES, and other cytokines which cause the accumulation of CCR5+ Th1 cells.
11745396 Selective induction of CCL18/PARC by staphylococcal enterotoxins in mononuclear cells and 2001 Dec Chemokines are mediators of innate and acquired immunity. CCL18, also designated pulmonary and activation-regulated chemokine (PARC), dendritic cell-derived CC chemokine-1 (DC-CK1), alternative macrophage activation-associated CC chemokine-1 (AMAC-1) and macrophage inflammatory protein-4 (MIP-4), was for the first time isolated from peripheral blood mononuclear cells (PBMC) and biochemically characterized. We found that CCL18/PARC protein is spontaneously secreted by PBMC and is selectively induced in PBMC by staphylococcal enterotoxins (SEA, SEB) and IL-4, but not by IFN-gamma and the CXCL8/IL-8 inducers lipopolysaccharide (LPS) or Concanavalin A. Human fibroblasts, chondrocytes and endothelial cells did not produce CCL18/PARC in response to inflammatory mediators such as measles virus, double-stranded RNA, LPS or IL-1beta, whereas up to 150 ng/ml of CCL2/MCP-1 was induced under these conditions. In synovial fluids from septic and rheumatoid arthritis patients, fourfold-enhanced CCL18/PARC levels (150 ng/ml) were detected compared to those in crystal-induced arthritis and osteoarthritis. In septic arthritis, the synovial levels of CCL18/PARC were fivefold higher than those of CXCL8/IL-8. Immunochemistry revealed CD68(+) monocytes/macrophages as the main CCL18/PARC-producing cell type in both PBMC and arthritic synovial tissue. In addition, CD1a(+) blood dendritic cells expressed CCL18/PARC. These findings suggest that monocytic cells respond to Gram-positive bacterial infection by the production of CCL18/PARC in the synovial cavity.
11238672 Human monoclonal rheumatoid synovial B lymphocyte hybridoma with a new disease-related spe 2001 Mar 15 Joint-specific self-Ags are considered to play an important role in the induction of synovial T and B cell expansion in human rheumatoid arthritis (RA). However, the nature of these autoantigens is still enigmatic. In this study a somatically mutated IgG2 lambda B cell hybridoma was established from the synovial membrane of an RA patient and analyzed for its Ag specificity. A heptameric peptide of cartilage oligomeric matrix protein (COMP) could be characterized as the target structure recognized by the human synovial B cell hybridoma. The clonotypic V(H) sequences of the COMP-specific hybridoma could also be detected in synovectomy material derived from five different RA patients but in none of the investigated osteoarthritis cases (n = 5), indicating a preferential usage of V(H) genes closely related to those coding for a COMP-specific Ag receptor in RA synovial B cells. Moreover, the COMP heptamer was preferentially recognized by circulating IgG in RA (n = 22) compared with osteoarthritis patients (n = 24) or age-matched healthy controls (n = 20; both p < 0.0001). Hence, the COMP-specific serum IgG is likely to reflect local immune responses toward a cartilage- and tendon-restricted Ag that might be crucial to the induction of tissue damage in RA.
11406520 Effects of treatment with a fully human anti-tumour necrosis factor alpha monoclonal antib 2001 Jul OBJECTIVES: To study the short term effects of a single dose of D2E7, a fully human anti-tumour necrosis factor (TNFalpha) monoclonal antibody (mAb), on the local and systemic homeostasis of interleukin 1beta (IL1beta) and TNFalpha in patients with rheumatoid arthritis (RA). METHODS: All patients with RA enrolled in a phase I, single dose, placebo controlled study with D2E7 in our centre were studied. Systemic cytokine levels, acute phase reactants, and leucocyte counts were studied at days 0, 1, and 14 after the first administration of anti-TNF mAb (n=39) or placebo (n=11). The cellularity and the expression of IL1 and TNFalpha in synovial tissue were studied in knee biopsy specimens obtained at baseline and at day 14 in 25 consenting patients. RESULTS: A single dose of anti-TNF mAb induced a rapid clinical improvement, a decrease in acute phase reaction, and increased lymphocyte counts in patients with active RA. The protein levels of IL1beta in the circulation were low and remained unchanged, but the systemic levels of IL1beta mRNA (p=0.002) and the concentrations of IL1 receptor antagonist (IL1ra) and IL6 (p=0.0001) had already dropped within 24 hours and this persisted up to day 14. Systemic levels of TNFalpha mRNA were low and remained unchanged, though total TNFalpha (free and bound) in the circulation increased after D2E7, probably reflecting the presence of TNF-antiTNF mAb complexes (p<0.005, at days 1 and 14). Both TNF receptors dropped below baseline levels at day 14 (p<0.005). Despite clinical improvement of arthritis, no consistent immunohistological changes were seen two weeks after anti-TNF administration. Endothelial staining for IL1beta tended to decrease in treated patients (p=0.06) but not in responders. The staining for IL1beta and TNFalpha in sublining layers and vessels was mutually correlated (r(s)=0.47 and 0.58 respectively, p<0.0005) and the microscopic scores for inflammation correlated with sublining TNFalpha and IL1beta scores (r(s)=0.65 and 0.54 respectively, p<0.0001), though none of these showed significant changes during the study. CONCLUSIONS: Blocking TNFalpha in RA results in down regulation of IL1beta mRNA at the systemic level and in reduction of the endogenous antagonists for IL1 and TNF and of other cytokines related to the acute phase response, such as IL6, within days. At the synovial level, anti-TNF treatment does not modulate IL1beta and TNFalpha in the short term. The synovial expression of these cytokines does not reflect clinical response to TNF neutralisation.
10648927 Phage antibodies against human dendritic cell subpopulations obtained by flow cytometry-ba 1999 Dec 10 In one application of phage display technology, large libraries of antibody fragments displayed on phage particles are used to select antibodies that bind to molecules expressed on the surface of eukaryotic cells. The advantage of this method is that antibodies can be selected against antigens in their native configuration, without the need to purify or express the antigen as a recombinant protein. Moreover, this approach may be used to search for novel membrane molecules expressed by subpopulations of cells that are difficult to address by conventional methods, e.g., small numbers of cells present in heterogeneous mixtures. It has been shown that the isolation of cell-bound phages is compatible with immunofluorescence staining and flow cytometric identification and sorting of cells based on multiparameter analysis. Here, we have employed a semi-synthetic phage display library of human single-chain Fv (scFv) antibody fragments in combination with flow cytometry to isolate antibodies against rare populations of precursor and mature dendritic cells (DCs) present in human peripheral blood. DCs are a phenotypically heterogeneous population of professional antigen presenting cells of bone marrow origin with complex and only partly understood developmental relationships and functions. We have isolated phage antibodies against subpopulations of blood DCs and analyzed the distribution of the target antigens. The results show that these phage antibodies are useful tools to further dissect relationships and function of DCs in healthy and diseased tissues.
9187965 Differential effects of cell density on 5-lipoxygenase (5-LO), five-lipoxygenase-activatin 1997 Apr We have analyzed the effect of cellular density of 5-Lipoxygenase (5-LO), 5-lipoxygenase-activating protein (FLAP) and interleukin-1 beta (IL-1 beta) gene expression in neutrophils from healthy subjects under culture conditions of low and high cell density. By using RT-PCR techniques, we have found that 5-LO mRNA accumulation decreased in cells cultured at high density, while FLAP mRNA is not affected. De novo 5-LO synthesis, as well as steady-state levels, were reduced in cells maintained at high density. In contrast, the high density conditions lead to the induction of IL-1 beta gene at the RNA and protein levels as measured by RT-PCR and by immunoprecipitation. These results suggest that cellular density plays a role in gene modulation when neutrophils are accumulating at an inflammatory site since neutrophils obtained from the synovial fluid of patients with RA exhibit a protein synthesis profile similar to that observed in peripheral blood neutrophils cultured at high density.
11171682 Heavy cigarette smoking is strongly associated with rheumatoid arthritis (RA), particularl 2001 Mar OBJECTIVES: To investigate the potential relation between cumulative exposure to cigarette smoking in patients with or without rheumatoid arthritis (RA) and a positive family history of the disease. METHODS: 239 outpatient based patients with RA were compared with 239 controls matched for age, sex, and social class. A detailed smoking history was recorded and expressed as pack years smoked. Conditional logistic regression was used to calculate the association between RA and pack years smoked. The patients with RA were also interviewed about a family history of disease and recorded as positive if a first or second degree relative had RA. The smoking history at the time of the study of the patients with RA with or without a family history of the disease was compared directly with that of their respective controls. Patients with RA with or without a family history of the disease were also compared retrospectively for current smoking at the time of disease onset. RESULTS: An increasing association between increased pack years smoked and RA was found. There was a striking association between heavy cigarette smoking and RA. A history for 41-50 pack years smoked was associated with RA (odds ratio (OR) 13.54, 95% confidence interval (95% CI) 2.89 to 63.38; p<0.001). The association between ever having smoked and RA was modest (OR 1.81, CI 1.22 to 2.19; p=0.002). Furthermore, cigarette smoking in the patients with RA without a positive family history of RA was more prevalent than in the patients with a positive family history of RA for ever having smoked (72% v 54%; p=0.006), the number of pack years smoked (median 25.0 v 4.0; p<0.001), and for smoking at the time of disease onset (58% v 39%; p=0.003). CONCLUSIONS: Heavy cigarette smoking, but not smoking itself, is strongly associated with RA requiring hospital follow up and is markedly more prevalent in patients with RA without a family history of RA.