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Objectives: HLA-DRB1*03 is strongly associated with anti-Jo-1-positive idiopathic inflammatory myopathies (IIM) and there is now increasing evidence that Jo-1 antigen is preferentially expressed in lung tissue. This study examined whether smoking was associated with the development of anti-Jo-1 antibodies in HLA-DRB1*03-positive IIM., Methods: IIM cases were selected with concurrent information regarding HLA-DRB1 status, smoking history and anti-Jo-1 antibody status. DNA was genotyped at DRB1 using a commercial sequence-specific oligonucleotide kit. Anti-Jo-1 antibody status was established using a line blot assay or immunoprecipitation., Results: 557 Caucasian IIM patients were recruited from Hungary (181), UK (99), Sweden (94) and Czech Republic (183). Smoking frequency was increased in anti-Jo-1-positive IIM cases, and reached statistical significance in Hungarian IIM (45% Jo-1-positive vs 17% Jo-1-negative, OR 3.94, 95% CI 1.53 to 9.89, p<0.0001). A strong association between HLA-DRB1*03 and anti-Jo-1 status was observed across all four cohorts (DRB1*03 frequency: 74% Jo-1-positive vs 35% Jo-1-negative, OR 5.55, 95% CI 3.42 to 9.14, p<0.0001). The frequency of HLA-DRB1*03 was increased in smokers. The frequency of anti-Jo-1 was increased in DRB1*03-positive smokers vs DRB1*03-negative non-smokers (42% vs 8%, OR 7.75, 95% CI 4.21 to 14.28, p<0.0001) and DRB1*03-positive non-smokers (42% vs 31%, p=0.08). In DRB1*03-negative patients, anti-Jo-1 status between smokers and non-smokers was not significantly different. No significant interaction was noted between smoking and DRB1*03 status using anti-Jo-1 as the outcome measure., Conclusion: Smoking appears to be associated with an increased risk of possession of anti-Jo-1 in HLA-DRB1*03-positive IIM cases. The authors hypothesise that an interaction between HLA-DRB1*03 and smoking may prime the development of anti-Jo-1 antibodies.

Objectives: Autoantibodies to a novel autoantigen small ubiquitin-like modifier activating enzyme (SAE) associated with dermatomyositis (DM) have previously been identified. The aim of this study was to establish the frequency of anti-SAE autoantibodies in a UK myositis cohort and investigate clinicoimmunogenetic associations., Methods: Clinical data and sera were studied from 266 patients recruited to the Adult Onset Myositis Immunogenetic Collaboration. Myositis sera, control sera including 250 patients with other connective tissue diseases and 50 healthy participants were screened using radio-immunoprecipitation. Immunodepletion was performed on all sera immunoprecipitating 40 and 90 kDa bands to confirm the presence of anti-SAE. DNA from 202 patients with myositis was genotyped for human leucocyte antigen (HLA)-DRB1 and DQB1; DQA1 data were inferred., Results: Out of 266 patients with myositis, 11 (4%) were positive for anti-SAE, which was found exclusively in DM with a frequency of 8%. Patients with anti-SAE had a high frequency of cutaneous lesions including heliotrope (82%) and Gottron rash (82%). Of the 11, 9 (82%) had systemic features and 7 of 9 (78%) developed dysphagia. Of those nine, seven (78%) presented with skin disease before myositis onset. All patients with anti-SAE possessed at least one copy of HLA-DQB1*03. HLA-DRB1*04-DQA1*03-DQB1*03 was a significant risk factor in anti-SAE positive versus patients who were anti-SAE negative (haplotype frequency 18% vs 6%, p<0.001, OR 5.7, 95% CI 1.9 to 17.3)., Conclusions: Anti-SAE is a myositis-specific autoantibody that identifies a subset of patients with adult DM. The majority of patients with anti-SAE presented with cutaneous disease and progressed to myositis with systemic features including dysphagia. This novel autoantibody has a strong association with the HLA-DRB1*04-DQA1*03-DQB1*03 haplotype.

Objective: To develop comprehensive recommendations for the treatment of the various clinical manifestations of psoriatic arthritis (PsA) based on evidence obtained from a systematic review of the literature and from consensus opinion., Methods: Formal literature reviews of treatment for the most significant discrete clinical manifestations of PsA (skin and nails, peripheral arthritis, axial disease, dactylitis and enthesitis) were performed and published by members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Treatment recommendations were drafted for each of the clinical manifestations by rheumatologists, dermatologists and PsA patients based on the literature reviews and consensus opinion. The level of agreement for the individual treatment recommendations among GRAPPA members was assessed with an online questionnaire., Results: Treatment recommendations were developed for peripheral arthritis, axial disease, psoriasis, nail disease, dactylitis and enthesitis in the setting of PsA. In rotal, 19 recommendations were drafted, and over 80% agreement was obtained on 16 of them. In addition, a grid that factors disease severity into each of the different disease manifestations was developed to help the clinician with treatment decisions for the individual patient from an evidenced-based perspective., Conclusions: Treatment recommendations for the cardinal physical manifestations of PsA were developed based on a literature review and consensus between rheumatologists and dermatologists. In addition, a grid was established to assist in therapeutic reasoning and decision making for individual patients. It is anticipated that periodic updates will take place using this framework as new data become available.

Objective: To conduct a case-control study to investigate whether there are independent tumour necrosis factor alpha (TNFalpha) or lymphotoxin alpha (LTalpha) haplotype associations with SLE or with any of the major serological subsets of SLE., Methods: 157 patients with SLE were genotyped for HLA-DRB1, HLA-DQB1, TNFalpha, and LTalpha alleles by polymerase chain reaction and compared with 245 normal white controls. For TNFalpha, six single nucleotide polymorphisms (SNPs) at positions -1031, -863, -857, -308, -238, and +488 and for LTalpha three SNPs at positions +720, +365, and +249 were studied to assign six TNFalpha haplotypes (TNF1-6) and four LTalpha haplotypes (LTA1-4). All SLE patients had full serological profiles on serial samples., Results: The most significant association with SLE overall was with HLA-DR3 (p<0.001; odds ratio (OR) = 2.5 (95% confidence interval, 1.6 to 3.8)) and the extended haplotype HLA-DQB1*0201;DRB1*0301;TNF2;LTA2 (p<0.001; OR = 2.3 (1.4 to 3.7)). Associations were strongest in the anti-La positive group (13%) of SLE patients (HLA-DR3, OR = 71 (9 to 539); HLA-DQB1*0201, OR = 35 (5 to 267); TNF2, OR = 10 (2.8 to 36), and LTA2, OR = 4.9 (1.1 to 21)). There was an increase in the HLA-DR2 associated extended haplotype (HLA-DQB1*0602;DRB1*1501;TNF1;LTA1) in patients with anti-Ro in the absence of anti-La (p<0.005; OR = 3.9 (1.5 to 10)). The HLA-DR7 extended haplotype (HLA-DQB1*0303;DRB1*0701/2;TNF5;LTA3) was decreased in SLE overall (p<0.02; OR = 0.2 (0.05 to 0.8))., Conclusions: The strongest association in this predominantly white population with SLE was between HLA-DR3 and anti-La, which seemed to account for any associations with TNFalpha alleles on an extended DR3 haplotype.

Objective: To develop criteria for disease activity in systemic sclerosis (SSc) that are valid, reliable, and easy to use., Methods: Investigators from 19 European centres completed a standardised clinical chart for a consecutive number of patients with SSc. Three protocol management members blindly evaluated each chart and assigned a disease activity score on a semiquantitative scale of 0-10. Two of them, in addition, gave a blinded, qualitative evaluation of disease activity ("inactive to moderately active" or "active to very active" disease). Both these evaluations were found to be reliable. A final disease activity score and qualitative evaluation of disease activity were arrived at by consensus for each patient; the former represented the gold standard for subsequent analyses. The correlations between individual items in the chart and this gold standard were then analysed., Results: A total of 290 patients with SSc (117 with diffuse SSc (dSSc) and 173 with limited SSc (lSSc)) were enrolled in the study. The items (including Delta-factors-that is, worsening according to the patient report) that were found to correlate with the gold standard on multiple regression were used to construct three separate 10-point indices of disease activity: (a) Delta-cardiopulmonary (4.0), Delta-skin (3.0), Delta-vascular (2.0), and Delta-articular/muscular (1.0) for patients with dSSc; (b) Delta-skin (2.5), erythrocyte sedimentation rate (ESR) >30 mm/1st h (2.5), Delta-cardiopulmonary (1.5), Delta-vascular (1.0), arthritis (1.0), hypocomplementaemia (1.0), and scleredema (0.5) for lSSc; (c) Delta-cardiopulmonary (2.0), Delta-skin (2.0), ESR >30 mm/1st h (1.5), total skin score >20 (1.0), hypocomplementaemia (1.0), scleredema (0.5), digital necrosis (0.5), Delta-vascular (0.5), arthritis (0.5), TLCO <80% (0.5) for all patients with SSc. The three indexes were validated by the jackknife technique. Finally, receiver operating characteristic curves were constructed in order to define the value of the index with the best discriminant capacity for "active to very active" patients., Conclusions: Three feasible, reliable, and valid preliminary indices to define disease activity in SSc were constructed.

Objective: To investigate the existence of differences among European referral centres for systemic sclerosis (SSc) in the pattern of attendance and referral and in the clinical and therapeutical approaches., Methods: In 1995 the European Scleroderma Study Group initiated a multicentre prospective one year study whose aim was to define the disease activity criteria in SSc. During the study period each participating European centre was asked to enroll consecutive patients satisfying American College of Rheumatology criteria for SSc and to fill out for each of them a standardised clinical chart. Patients from various centres were compared and differences in epidemiological, clinical, and therapeutical aspects were analysed., Results: Nineteen different medical research centres consecutively recruited 290 patients. The patients could be divided into two subgroups: 173 with the limited (lSSc) and 117 with the diffuse (dSSc) form of the disease. The clinical and serological findings for the series of 290 patients seemed to be similar to data previously reported. However, when the data were analysed to elicit any differences between the participating centres, a high degree of variability emerged, in both epidemiological and clinical features and in the diagnostic and therapeutic approaches to the disease., Conclusions: The clinical approach to SSc, not only in different countries but also in different centres within the same country, is not yet standardised. To overcome this problem, it will be necessary for the scientific community to draw up a standardised procedure for the management of patients with SSc. This would provide a common research tool for different centres engaged in research on this complex disease.

Objectives: (a) To characterise the lipid profile in psoriatic arthritis and investigate whether there are similarities to the dyslipoproteinaemia reported in rheumatoid arthritis and other inflammatory forms of joint disease; (b) to investigate whether there is an atherogenic lipid profile in psoriatic arthritis, which may have a bearing on mortality., Methods: Fasting lipids, lipoproteins, and their subfractions were measured in 50 patients with psoriatic arthritis and their age and sex matched controls., Results: High density lipoprotein cholesterol (HDL cholesterol) and its third subfraction, HDL(3) cholesterol, were significantly reduced and the most dense subfraction of low density lipoprotein (LDL), LDL(3), was significantly increased in the patients with psoriatic arthritis. Twenty patients with active synovitis had significantly lower total cholesterol, LDL cholesterol, and HDL(3) cholesterol than their controls. 25% of the patients with psoriatic arthritis had raised Lp(a) lipoprotein levels (>300 mg/l) compared with 19% of controls, but this was not statistically significant., Conclusion: Raised levels of LDL(3) and low levels of HDL cholesterol are associated with coronary artery disease. Such an atherogenic profile in a chronic inflammatory form of arthritis is reported, which may be associated with accelerated mortality.