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ID PMID Title PublicationDate abstract
9856769 Characterization of two corneal epithelium-derived antigens associated with vasculitis. 1998 Dec PURPOSE: In a previous investigation into corneal autoimmunity, it was demonstrated that a putative autoantigen, a protein of 66 kDa, present in bovine corneal epithelium, binds circulating autoantibodies in approximately 60% of patients with Wegener's granulomatosis (WG). The aim of the present study was to characterize and identify the 66-kDa protein. METHODS: A purification protocol was established for the 66-kDa protein using standard chromatography techniques. During the purification procedure it became clear that the 66-kDa protein detected in patients' sera was in fact two proteins, both running at 66 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, that eluted in different fractions on DE-52 chromatography columns. These two proteins have been labeled bovine corneal epithelial antigen-A and -B (BCEA-A and BCEA-B). Further investigations of antibody binding have demonstrated that patients' sera bind to either one or the other of these proteins with no cross-reactivity between them. Separated BCEA-A and BCEA-B protein extracts were immunoblotted with 27 WG patients' sera, 10 Churg-Strauss syndrome (CSS) patients' sera, 31 rheumatoid arthritis (RA) patients' sera, and 40 healthy control subjects' sera from the blood bank. RESULTS: Forty-six percent of WG patients' sera had antibodies to one of the 66-kDa antigens, whereas none of the healthy control subjects' sera had 66-kDa antibodies (P < 10(-5)). In the WG group, 31% were positive to BCEA-A (versus controls, P = 0.0023), and 15% were positive to BCEA-B. WG patients with peripheral ulcerative keratitis (PUK) had a significant association with anti-BCEA-A antibodies when compared with healthy control subjects (50%, P < 10(-6)). However, in the RA group with no eye disease there was an association with BCEA-A (25%, P = 0.011) but not in the RA group with PUK. The frequency of anti-BCEA-B antibodies was significantly increased in patients with CSS (60%, P < 10(-7)). CONCLUSIONS: In summary, it has been shown that vasculitis patients have antibodies to two 66-kDa corneal antigens and that autoantibodies to these antigens are mutually exclusive. It has also been shown that antibodies to BCEA-B are associated with CSS, whereas BCEA-A antibodies are associated with WG and RA.
9456017 Cutaneous necrotizing vasculitis after low dose methotrexate therapy for rheumatoid arthri 1997 Nov Large haemorrhagic and necrotic cutaneous lesions developed after two low dose (5 mg) methotrexate injections in a patient suffering from long standing rheumatoid arthritis. Differential clinical diagnosis included factitia dermatitis, infectious processes, pyoderma gangrenosum, rheumatoid neutrophilic dermatitis, necrotizing arteritis and vasculitis. Histological and direct immunofluorescent examinations of skin biopsies supported the diagnosis of leucocytoclastic vasculitis. We discuss the respective roles of methotrexate and rheumatoid arthritis in the outbreak of leucocytoclastic vasculitis. Hypersensitivity is strongly suspected.
9585924 [The rheumatic hand]. 1998 Mar The hand (wrist and fingers) is one of the regions most frequently affected by rheumatic arthritis (RA). The nature of the alterations involved means it is possible to interpret the clinical picture as RA even from the external appearance. Obviously the functional handicap affects activities of daily living, and the insult to the patient's aesthetic sensibilities imposes an additional, psychological, burden. A generally satisfactory limitation of damage can only be expected from professionals who work well together as a team. The ability to devise a therapy plan with the right priorities is the mark of those who have mastered the art of surgery for rheumatic conditions. Operative treatment presupposes failure of a conservative therapy carried out according to modern views. In addition to operations on the affected joints, operations on the tendons of the hand are also highly significant in terms of function. The interventions that can be performed on the joints embrace synovectomies, arthroplasties and arthrodeses. In the last 20 years the absolute number of joint synovectomies has fallen, since at least in treatment of the early stages radiosynoviorthesis has become increasingly important, especially for the metacarpophalangeal (MP) and proximal interphalangeal (PIP) joints. Operative synovectomy is now considered when radiosynoviorthesis fails or in more advanced stages (Larsen 3) and when reconstruction procedures (especially on the tendons) are necessary. The chances are also better with open synovectomy (with or without resection of the head of the ulna) at the wrist. The results of synovectomy are not so impressive from the radiological aspect as from the clinical viewpoint, since as a result of the removal or attenuation of pain the function is often improved to the status of more than 10 years before and valuable time is thus gained. When the destruction is too far advanced arthroplasty is considered, especially for the MP joints but increasingly also for the PIP joints. Arthrodesis is a still highly valuable procedure for the wrist, since there is no really satisfactory artificial joint. An arthroplasty can only be successful if the tendons are intact. Tenosynovectomy and repair of ruptures have a good prognosis if appropriate techniques are used. The correction of such typical deformities of the fingers as buttonhole and swan neck deformity requires some of the technically more demanding operations.
11094417 A new model for rheumatoid arthritis? 2000 A chance observation has led to the development of a new murine model for inflammatory arthritis. Arthritis is induced, and transferred, by T-cell-dependent antibodies to glucose-6-phosphate isomerase. This enzyme is expressed in all cells, and is detectable in serum. There are several similarities to rheumatoid arthritis (RA) in the murine disease. This elegant model raises several questions as to how and why a systemic response focuses inflammation so strongly on synovial joints. The model also re-introduces the possibility that antibodies to widely expressed self-proteins may play a role in the pathogenesis of RA.
9918234 Anti-Sa antibody is an accurate diagnostic and prognostic marker in adult rheumatoid arthr 1999 Jan OBJECTIVES: To evaluate in various groups of patients with chronic joint disease the sensitivity and specificity of anti-Sa antibody, recently described in sera from adults with rheumatoid arthritis (RA); and to determine the prognostic significance of anti-Sa in initial sera from patients with long standing RA with or without severe joint destruction. METHODS: Serum samples from 489 patients were included. Of these, 154 were collected from patients with RA attending 2 rheumatology units. Controls were 335 patients with a variety of inflammatory joint diseases other than RA. IgG anti-Sa was detected using an immunoblotting method with purified Sa antigen from human placenta extracts. All patients were tested for the following antibodies: rheumatoid factor (RF), anti-keratin antibody (AKA), antiperinuclear factor (APF), and anti-RA 33. HLA class II DRB alleles were also determined. RESULTS: Anti-Sa was detected in 39.8% of RA sera overall, 46.7% of sera from the long standing RA group, and 23.5% of sera from the recent onset RA group (p<0.01). In patients with long standing RA, statistically significant associations were found between the presence of anti-Sa and the following variables: RF (p<0.0001), AKA (p<0.0001), APF (p<0.00001), and HLA DRB1*04 or 01 (p<0.01). In contrast, no association was found with anti-RA33. Anti-Sa was positive in 11 adult controls (7.8%) and in 26 pediatric patients with juvenile chronic arthritis (22%). The specificity of anti-Sa for RA was 92.1% in adults with well characterized rheumatic diseases and 85.9% in adults and children together. Among patients with long standing RA, those with destructive disease were more likely to test positive for anti-Sa (66.6%) than those with nondestructive disease (22.2%) (p<0.0001). Comparisons with other serologic markers for RA demonstrated that anti-Sa was sensitive (68.4%) and was also the test with the highest specificity (79%), positive predictive value (75%), and negative predictive value (71%) for discriminating between patients who do and those that do not develop late severe radiographic damage. CONCLUSION: Immunoblot-detected IgG anti-Sa is a sensitive serologic marker for RA patients with severe radiographic damage.
10953411 [Hematopoietic stem cell transplantation in autoimmune diseases in rheumatology practice]. 2000 Jun 7 Autoimmune diseases (AID) result from the impairment of the effector and/or recognition phase of the immune response. The autoimmune process plays a crucial role in the pathogenesis of the systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), and their treatment is therefore largely based on immunosuppression. However, some patients do not respond to its standard doses. The disease becomes intractable with the survival rate comparable to that of some haematological malignancies, or patients become soon handicapped with very poor quality of life, depending on continual administration of high doses of steroids. The new hope for those patients becomes therapy with high dose myelo- and immuno-ablative chemotherapy with autologous hematopoietic progenitor cell support (PBPC). Tens of patients with intractable forms of AID were transplanted in the pilot clinical studies with promising results. The most frequent indications included: SLE, SSc, and RA. Final conclusion of the therapeutic effects will be drawn from the analysis of larger trails.
10952741 Radiolabelled interleukin-1 receptor antagonist for detection of synovitis in patients wit 2000 Aug OBJECTIVES: To investigate the distribution of radiolabelled interleukin-1 receptor antagonist (IL-1ra) in patients with rheumatoid arthritis (RA) and to assess whether this cytokine is suitable for scintigraphic visualization of synovitis. METHODS: In patients with active RA, scintigraphy was performed after a single i. v. dose of [(123)I]IL-1ra. Clearance and organ distribution of radiolabelled IL-1ra were studied. To assess whether radiolabelled IL-1ra targets the synovial IL-1 receptors, the scintigraphic images obtained with IL-1ra were compared with those obtained by the use of a non-specific control agent. In addition, autoradiography was performed in mice with antigen-induced arthritis that were injected with either radiolabelled IL-1ra or a size-matched, non-receptor-binding protein. RESULTS: Radiolabelled IL-1ra allowed clear visualization of inflamed joints. Specificity in the detection of synovitis was high, whereas a number of painful and swollen joints were not visualized by scintigraphy. The procedure was well tolerated and [(123)I]IL-1ra was rapidly cleared from the circulation (t(1/2)alpha 11 min, t(1/2)beta 612 min) and excreted mainly in the urine. The definition of synovial contours by IL-1ra scintigraphy was not better than that observed with a non-specific agent. Although radiolabelled IL-1ra retained its affinity for IL-1 receptors, no binding to synovium was observed by autoradiography. CONCLUSIONS: Radiolabelled IL-1ra allows the visualization of synovitis in patients with RA. However, neither the imaging nor the autoradiographic studies indicate that joint accumulation of radiolabelled IL-1ra is due to specific IL-1 receptor targeting. IL-1ra has proved its therapeutic value in RA, but with the dose schedule in this study it does not behave as a specific radiopharmaceutical that is suitable for scintigraphic detection of inflammation.
10403280 Production of interleukin-7 and interleukin-15 by fibroblast-like synoviocytes from patien 1999 Jul OBJECTIVE: To examine the ability of fibroblast-like synoviocytes in rheumatoid arthritis (RA) to produce interleukin-7 (IL-7) and IL-15, and the ability of these cytokines to induce the proliferation of synovium-infiltrating T cells. METHODS: Messenger RNA (mRNA) and protein levels of IL-7 and IL-15 in synovial tissue cells and fibroblast cell lines were determined by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. T cell-enriched populations from RA synovial tissues were isolated by deleting adherent cells after a 14-hour incubation in plastic dishes or by expanding T cells during a 14-day incubation of tissue cells with IL-2 alone, and their proliferative responses to IL-7, IL-15, and IL-2 were measured by 3H-thymidine incorporation. RESULTS: Freshly isolated cells from RA synovial tissues more strongly expressed mRNA for both IL-7 and IL-15 compared with the cells from osteoarthritis tissues, and could spontaneously release greater amounts of these cytokine proteins in culture. Fibroblast cell lines prepared from RA patients were able to produce large amounts of IL-15 and small amounts of IL-7 at both the transcriptional and protein levels, and their cytokine production was significantly elevated when stimulated with IL-1 and tumor necrosis factor alpha. Purified synovial tissue macrophages spontaneously released IL-15 but not IL-7, and synovial T cells did not produce either cytokine. IL-7 and IL-15, similar to IL-2, stimulated the proliferation of synovial tissue T cells from RA patients; IL-7 was less potent than IL-15 or IL-2. CONCLUSION: These results indicated that fibroblast-like synoviocytes are an important source of the cytokines with IL-2-like activity, IL-15 and IL-7, in RA joints, and that IL-15 may be mainly responsible for local T cell activation and expansion in the presence of deficient IL-2 production by T cells.
9041935 CD8high+ (CD57+) T cells in patients with rheumatoid arthritis. 1997 Feb OBJECTIVE: To investigate the development and T cell receptor (TCR) usage of CD8+, CD57+ T cells in rheumatoid arthritis (RA) patients. METHODS: Three-color flow cytometry using monoclonal antibodies (MAb) to CD8, CD57 and different TCR V beta gene products. RESULTS: The proportion of CD8+ T cells expressing CD57 (CD57/CD8) was significantly higher in RA patients compared with age-matched controls. Expanded TCR V beta populations were more frequent, and were found in both RA patient-derived CD8high+ (CD57+) and CD8+, CD57- populations. TCR V beta 5+ and TCR V beta 13+ expansions were present at high frequency (5 of 26 and 7 of 26, respectively). TCR V beta expansions in CD8high+ (CD57+) lymphocytes from RA patients were significantly larger than those in age-matched controls (expansion index 2.38 +/- 0.28, n = 41 and 1.63 +/- 0.09, n = 32, respectively), and were stable over time. CONCLUSION: RA leads to an increase in the frequency of expanded CD8+ T cell subsets expressing selected TCR, due to expansion of TCR V beta + populations in CD8high+ (CD57+) T cells. Their restricted TCR usage suggests potential specificity for RA antigens and, therefore, a potential role in the pathogenesis of RA.
10646486 Rheumatoid arthritis: new developments in the use of existing therapies. 1999 Nov Combination therapy with methotrexate may be the newest standard to which future therapies for rheumatoid arthritis are compared. Many questions remain to be answered regarding the appropriateness of such combination therapies for specific patients and clinical situations, and the optimal therapeutic combinations. Other unanswered questions regarding combination therapy include the need for appropriate monitoring, long-term safety and cost-benefit implications. Future research is needed to clarify the role of biological response modifiers (e.g. anti-tumour necrosis factor therapies) and matrix metalloproteinase inhibitors, both as components of and alternatives to methotrexate combination regimens.
9301317 [New strategies for treatment of rheumatoid arthritis]. 1997 Sep Rheumatoid arthritis(RA) is a chronic systemic inflammatory disease of unknown etiology, characterized by synovial inflammation and local tissue destruction. For many years, the traditional approach for the therapy of RA was the therapeutic pyramid. Recently, the beneficial effects of the pyramid strategy have been questioned because the long-term outcome of RA continues to be disappointing. Three developments stimulated a change in thinking: first, the increasingly precise understanding of pathogenesis, second, the availability of biological agents and, third, the methods of evaluation for RA therapy. Therefore, many treatment strategies for RA, almost of which prefer the earlier introduction of disease-modifying antirheumatic drugs, have been proposed. Several representative strategies are reviewed in this paper.
11216680 Diagnosing basilar invagination in the rheumatoid patient. The reliability of radiographic 2001 Feb BACKGROUND: Basilar invagination can be difficult to diagnose with plain radiography in patients with rheumatoid arthritis. Although numerous radiographic criteria have been described, few studies have addressed the reliability of these parameters in the rheumatoid population. The purpose of the present study was to validate and compare the most widely accepted plain radiographic criteria for basilar invagination in this patient population. METHODS: Cervical radiographs of 131 rheumatoid patients were examined. Of these patients, sixty-seven (twenty-nine with basilar invagination and thirty-eight without it) were also evaluated with tomograms, magnetic resonance imaging, and/or sagittally reconstructed computed tomography scans to detect the presence of basilar invagination. Three observers who were blinded with regard to the diagnosis independently scored each radiograph as positive, negative, or indeterminate according to the established criteria for invagination proposed by Clark et al., McRae and Barnum, Chamberlain, McGregor, Redlund-Johnell and Pettersson, Ranawat et al., Fischgold and Metzger, and Wackenheim. Interobserver and intraobserver variability, sensitivity, specificity, total percentage of correct results, and negative and positive predictive values were determined for each criterion as well as for various combinations of the criteria. RESULTS: No single test had a sensitivity and a negative predictive value of greater than 90% as well as a reasonable specificity and a reasonable positive predictive value. The combination of the Clark station, the Redlund-Johnell criterion, and the Ranawat criterion, scored as positive for basilar invagination if any of the three were positive, proved to be better than any single criterion; the sensitivity of the combined criteria was 94%, and the negative predictive value was 91%. CONCLUSIONS: A screening test for basilar invagination should have a high sensitivity and a high negative predictive value, so that the disease will not be missed, and yet be specific, so that the disease will not be overdiagnosed. Our data suggest that none of the widely utilized plain radiographic criteria meet these goals. We recommend that measurements be made according to the methods described by Clark et al., Redlund-Johnell et al., and Ranawat et al. and, if any of these suggests basilar invagination, tomography or magnetic resonance imaging should be performed. Since approximately 6% of the cases of basilar invagination in rheumatoid patients would still be missed with this approach, tomography or magnetic resonance imaging should be performed on a rheumatoid patient whenever plain radiographs leave any doubt about the diagnosis of basilar invagination.
10630759 Current treatment strategies for rheumatoid arthritis. 2000 Jan The management of rheumatoid arthritis has changed considerably during the past 15 years. Current strategies emphasize the need for early diagnosis and therapeutic intervention based on the use of disease-modifying antirheumatic drugs. The advent of agents that are more tailored to inhibit the specific disease processes will profoundly affect management. Immunogenetic studies may eventually assist in identifying subgroups of patients with rheumatoid arthritis who have more aggressive disease and who require a more aggressive treatment approach.
9133931 Mannan binding protein in sera positive for rheumatoid factor. 1997 Feb Low levels of mannan binding protein (MBP) may protect against rheumatoid arthritis and other inflammatory conditions associated with agalactosyl IgG. MBP concentrations were measured in 99 sera found to be positive for rheumatoid factor, at least 41 of which were from patients with rheumatoid arthritis, and the values compared to the data from 352 controls. MBP was undetectable in similar proportions of patients' and control sera (4.0 and 4.3%, respectively), and low values generally were similarly distributed in the two groups. Overall, however, the patient values were distorted upwards relative to controls, consistent with an acute-phase response. These findings do not refute the proposed role for MBP-agalactosyl IgG-mediated complement activation in the pathogenesis of rheumatoid arthritis, but certainly provide no support for that hypothesis.
11519428 [Impact of menopause and disease on osteocalcin markers in female patients with rheumatoid 2001 Mar The impact of menopause and activity of rheumatoid inflammation on the osseous tissue metabolism was studied with the aid of biochemical markers of remodelling of the osseous tissue. Osteocalcin (noncollagenous protein of bone tissue) is believed to be the most informative marker of formation of the osseous tissue. In 70 female patients presenting with rheumatoid arthritis, blood serum concentration of osteocalcin was measured. Of these, 37 were in their premenopause, 33--in postmenopause. The control group was 26 female subjects. The activity of the rheumatoid process in premenopausal period and during the postmenopausal second and third five-year periods was found out to be associated with the rate of processes of bone tissue formation. At menopause the blood content of osteocalcin gets increased but subsequently it is noted to be on the decrease.
9451199 Appropriate laboratory testing in rheumatic diseases. 1998 Jan The diagnosis and management of systemic rheumatic disease is predominantly based on clinical parameters. Nevertheless, specific laboratory diagnostic tests may often be critically helpful, for example, in ruling out septic and crystal-induced arthritis in the differential diagnosis of acute monoarthritis. In the evaluation of patients with polyarticular rheumatic disease syndromes, autoimmune testing may be helpful to corroborate the clinical diagnosis of such diverse illnesses as rheumatoid arthritis, systemic lupus erythematosus, Lyme disease, and anticardiolipin syndrome.
10025106 [Patient self-management and stabilization as a contribution to process quality]. 1998 Dec Self-management is described as a pattern of patient behavior dealing with chronic disease. It encompasses self-assessment, decision making, self-care and treatment as well as documentation. The self-management behavior has to be encouraged and supported by health care professionals.
9751090 Assessment of rheumatoid arthritis using a modified scoring method on digitized and origin 1998 Sep OBJECTIVE: The results of different readers' interpretations of laser-digitized hand radiographs versus original radiographs were compared to determine the reproducibility of scoring of erosions (ERO), joint space narrowing (JSN), and their combination (ERO + JSN) in patients with rheumatoid arthritis (RA). METHODS: Standardized radiographs of both hands were obtained at 2 visits (baseline and 6-24-month followup) from 30 patients with established RA. Conventional and laser-digitized (pixel sizes 50 microm and 100 microm) radiographs were scored independently by 3 experienced and trained radiologists who were blinded to the order of the visits. Scoring of radiographs was based on the validated Genant grading system. RESULTS: Intertechnique (intrareader) correlation coefficients at baseline were 0.90-0.93 for scoring of ERO, 0.90-0.94 for scoring of JSN, and 0.92-0.95 for ERO + JSN; for scoring of progression between baseline and followup, these values were 0.93-0.97, 0.87-0.95, and 0.93-0.97, respectively. Interreader (intratechnique) correlation coefficients at baseline were 0.82-0.96 for scoring of ERO, 0.69-0.91 for scoring of JSN, and 0.80-0.95 for ERO + JSN; for scoring of progression between baseline and followup, these values were 0.90-0.97, 0.80-0.92, and 0.90-0.95, respectively. Intrareader (intratechnique) correlation coefficients were 0.90-0.97 for scoring of the original radiographs and 0.90-0.98 for scoring of the digitized images at 100 microm. CONCLUSION: Using this modified grading system, scoring of RA progression directly from paired, high-resolution monitors of laser-digitized images of the hands provided highly reproducible results, comparable to those obtained from the original radiographs. Thus, this method may have useful applications in clinical trials involving RA.
10392517 Metacarpophalangeal joint arthroplasty in rheumatoid arthritis: results of Swanson implant 1999 We discuss 69 metacarpophalangeal (MP) implant arthroplasties performed in 30 patients with rheumatoid arthritis. The follow-up averaged 5 years. We studied 19 finger joint prostheses by Condamine, digital joint operative arthroplasty (stabilized version; DJOA) and 50 flexible silicone Swanson implants. We used a new comprehensive scoring system to evaluate the MP alloarthroplasties. Such a scoring system incorporates clinical and radiological data. The outcome following MP joint replacement with DJOA was never evaluated as 'good'; in 11 joints the result was 'fair', and in 8 joints, 'poor'. As regards MP arthroplasty with Swanson implants, the results were evaluated as 'good' in 40 joints, as 'fair' in 10 joints, and in none as 'poor'. In our series, DJOA did not provide stability in arthritic MP joints. In all joints replaced with DJOA, dislocation of the articulating surfaces and signs of loosening were present. We regard three factors as being the main causes contributing to the poor outcome of DJOA when used as MP replacements. Firstly, the proximal prosthetic component is poorly matched to the anatomical shape of the metacarpal bone (conisation of the bone). Secondly, adequate coaptation cannot be achieved with this prosthetic design, even in the presence of extensive soft-tissue reconstruction. Thirdly, the use of polyethylene in MP joint replacements is questionable. In contrast, the silicone Swanson implants in our series provided superior results when used as MP implants in the rheumatoid hand.
10446870 Association of HLA alleles and clinical features in patients with synovitis of recent onse 1999 Aug OBJECTIVE: To determine how HLA alleles are associated with the clinical disease patterns of patients with synovitis of recent onset. METHODS: The HLA alleles A, B, C, DRbeta1, and DQbeta1 were determined in a cohort of 211 patients (mean age 42 years, 64% female, 79% white) with recent-onset synovitis in 1 or more peripheral joints. At a mean disease duration of 33 weeks, 98 patients (46%) met the American College of Rheumatology (ACR) criteria for rheumatoid arthritis (RA), 38 (18%) met the European Spondylarthropathy Study Group criteria for spondylarthropathy (SpA), and 75 (36%) were classified as having undifferentiated arthropathy (UA). Controls were racially matched healthy individuals (n = 244). RESULTS: Shared epitope (SE) alleles were significantly more common in rheumatoid factor-positive (RF+) patients fulfilling the ACR RA criteria than in other patients with early arthritis (65% versus 35%; P < 0.001). In addition, the RA patients had by far the highest frequency of radiographic erosions (52% and 39% in RF+ and RF- RA, respectively, versus 3% and 9% in SpA and UA patients, respectively; P < 0.0001). The presence of SE alleles was a particularly strong predictor of early erosions in the RF- RA patients (odds ratio [OR] 6.8, 95% confidence interval [95% CI] 1.2-45). The presence of 2 SE alleles or an associated DQbeta1*0301 (DQ7) or DQbeta1*0302 (DQ8) allele appeared to modestly increase the risk of early erosions, although these DQ alleles were in strong linkage disequilibrium with DRbeta1*0401, both in the patient and in the control populations. B27 was linked with the presence of SE alleles in the patients, including those patients fulfilling the RA criteria, but not in the controls (12% versus 3%; P < 0.001). Enthesitis was present in 23 (11%) of 211 patients, was highly associated with B27 (OR 4.2, 95% CI 1.5-11.5), and surprisingly, was not a feature specific only to the SpA group. The B8-DR3 haplotype was significantly increased in the patient subgroups compared with controls (17% versus 7%; P < 0.01), although the clinical significance of this association is unclear. CONCLUSION: This study of HLA associations in a diverse cohort of early synovitis patients emphasizes the complex degree of genetic interaction between alleles at several major histocompatibility complex loci, which regulates clinical phenotypes. In particular, SE and B27, while predisposing patients to characteristic clinical syndromes, had an unexpected degree of association in this cohort, perhaps explaining the overlap in clinical features in many patients.