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Originally developed as research tools, different classification criteria sets for systemic lupus erythematosus (SLE) are also used to diagnose SLE in routine clinical care. The recently developed European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2019 criteria set is noted to perform better than previous SLE classification criteria. This study applied the new criteria schema to a tertiary center SLE cohort, ascertained its performance, and identified the clinical characteristics of patients who did not fulfill these criteria. From the 217 patients who were included, 11 (5%) did not meet the new criteria, mainly because of the antinuclear antibody entry criterion, resulting in a diagnostic sensitivity of 94%. Within this group, we found that constitutional and renal manifestations were unusual. Additionally, specific SLE antibodies as well as hypocomplementemia were less likely to be present. We did not observe a statistically significant difference in outcomes between the two groups of patients (fulfilling vs. unfulfilling the new criteria). We conclude that the EULAR/ACR criteria may misclassify a small subset of SLE patients with milder disease. It is important to be cognizant of key clinical and serologic features of these patients and treat them accordingly to prevent further irreversible damage.

Objective: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR)., Methods: This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects., Results: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria., Conclusion: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research., (© 2019, American College of Rheumatology.)

Objective: To define candidate criteria within multiphase development of systemic lupus erythematosus (SLE) classification criteria, jointly supported by the American College of Rheumatology and the European League Against Rheumatism. Prior steps included item generation and reduction by Delphi exercise, further narrowed to 21 items in a nominal group technique exercise. Our objectives were to apply an evidence-based approach to the 21 candidate criteria, and to develop hierarchical organization of criteria within domains., Methods: A literature review identified the sensitivity and specificity of the 21 candidate criteria. Data on the performance of antinuclear antibody (ANA) as an entry criterion and operating characteristics of the candidate criteria in early SLE patients were evaluated. Candidate criteria were hierarchically organized into clinical and immunologic domains, and definitions were refined in an iterative process., Results: Based on the data, consensus was reached to use a positive ANA of ≥1:80 titer (HEp-2 cells immunofluorescence) as an entry criterion and to have 7 clinical and 3 immunologic domains, with hierarchical organization of criteria within domains. Definitions of the candidate criteria were specified., Conclusion: Using a data-driven process, consensus was reached on new, refined criteria definitions and organization based on operating characteristics. This work will be followed by a multicriteria decision analysis exercise to weight criteria and to identify a threshold score for classification on a continuous probability scale., (© 2017, American College of Rheumatology.)

Objectives: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches., Methods: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival., Results: Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months., Conclusions: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed., Trial Registration Number: NCT02339441., Competing Interests: Competing interests: ALH has done consultancy work for Actelion, served on a Data Safety Monitoring Board for Apricus, received research funding and speaker's fees from Actelion, and speaker's fees from GSK. JHWD has consultancy relationships and/or has received research funding from Actelion, BMS, Celgene, Bayer Pharma, Boehringer Ingelheim, JB Therapeutics, Sanofi-Aventis, Novartis, UCB, GSK, Array Biopharma, Active Biotech, Galapagos, Inventiva, Medac, Pfizer, Anamar and RuiYi and is stock owner of 4D Science GmbH. OD has received consultancy fees from 4D Science, Actelion, Active Biotech, Bayer, Biogenidec, BMS, Boehringer Ingelheim, EpiPharm, Ergonex, espeRare Foundation, Genentech/Roche, GSK, Inventiva, Lilly, Medac, Medimmune, Pharmacyclics, Pfizer, Serodapharm, and Sinoxa and received research grants from Actelion, Bayer, Boehringer Ingelheim, Ergonex, Pfizer and Sanofi, and has a patent mir-29 for the treatment of systemic sclerosis licenced. WG has received teaching fees from Pfizer. FH has received research funding from Actelion. MEA has undertaken advisory board work and received honoraria from Actelion, and received speaker's fees from Bristol-Myers Squibb. LC has done advisory board work for Gilead and served Data Safety Monitoring Boards for Cytori and Reata. HG has done consultancy work and received honoraria from Actelion. UM-L is funded in part bu EUSTAR/EULAR. JMvL has received honoraria from Eli Lilly, Pfizer, Roche, MSD and BMS. AR receives funding from AstraZeneca. CPD has done consultancy for GSK, Actelion, Bayer, Inventiva and Merck-Serono, received research grant funding from GSK, Actelion, CSL Behring and Inventiva, received speaker's fees from Bayer and given trial advice to Merck-Serono., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Autoantibodies against several aminoacyl-transfer-RNA synthetases have been described in patients with myositis; anti-threonyl-tRNA synthetase (anti-PL-7) is one of the rarest. We describe the clinical and laboratory characteristics of a cohort of European anti-PL-7 patients, and compare them with previously reported cases. This multicenter study of patients positive for anti-PL-7, identified between 1984 and 2011, derives from the EUMYONET cohort. Clinical and serologic data were obtained by retrospective laboratory and medical record review, and statistical analyses were performed with chi-squared and Fisher exact tests. Eighteen patients, 15 women, were anti-PL-7 antibody positive. Median follow-up was 5.25 years (interquartile range, 2.8-10.7 yr), and 4 patients died. All patients had myositis (12 polymyositis, 5 dermatomyositis, and 1 amyopathic dermatomyositis), 10 (55.6%) had interstitial lung disease, and 9 (50%) had pericardial effusion. Occupational exposure to organic/inorganic particles was more frequent in patients with interstitial lung disease than in the remaining patients (5 of 10 vs. 1 of 7; p = 0.152), although the difference was not significant. Concurrent autoantibodies against Ro60 and Ro52 were seen in 8 of 14 (57%) patients studied. In the literature review the most common manifestations of anti-PL-7 antisynthetase syndrome were interstitial lung disease (77%), myositis (75%), and arthritis (56%). As in other subsets of the antisynthetase syndrome, myositis and interstitial lung disease are common features of the anti-PL-7 antisynthetase syndrome. In addition, we can add pericarditis as a possible manifestation related to anti-PL-7 antibodies.

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.

The choice of terms used to describe indirect immunofluorescence (IIF) staining patterns of autoantibodies binding to HEp-2 cells is at present quite varied and disordered because no accurate consensus on names and descriptions exist. The aim of our study was to propose a logical and ordered IIF classification taxonomy based on 29 different selected IIF patterns. In a preliminary project carried out at Statens Serum Institut it was first shown by use of a software programme named DOORS developed by Percepton Ltd, that reading of digitized images of HEp-2 patterns on an LCD monitor could be used instead of traditional microscopy. Digitized images of HEp-2 patterns were then used in the EU supported project named CANTOR (June 1998-July 2000) aiming to reach consensus among three clinical immunology expert centres and collaborating to attain a classification version that could be used to qualitatively and quantitatively test and train image recognitions skills of laboratory technicians against expert consensus. The usability of this classification version was then tested in a course consisting of training and certification. The conclusion was that participants in the training programme clearly increased their perceptive skills using images, terms, descriptions and the graphic and statistic tools in the self-administered DOORS programme and that software-assisted training could achieve a common and accurate level of visual pattern interpretation. All results from this project were reported to the European Commission but have not previously been published in scientific literature. This communication presents the final results of agreed image classifications., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

SSc with ACAs is characterized by limited cutaneous involvement and, in most patients, a mild protracted course. We have studied 104 SSc patients, 47 with ACAs and 57 who were negative for both ACAs and anti-topo I antibodies, for HLA-DR and -DQ associations using DNA typing techniques. Normal controls consisted of 181 healthy individuals. A significant association was observed in the ACA-positive patients with DQB1-0501 (p = 0.001, RR 2.6). There was also a significant decrease in the frequency of DQB1-0201 (p = 0.01, RR 0.33). In addition, the ACA-positive SSc patients were significantly different ethnically from both the other SSc patients and the normal controls (p = 0.004). When patients were stratified according to their ethnic origin and the analysis of HLA associations was repeated, the HLA associations persisted. These results strongly suggest that the development of SSc with ACAs is associated with particular DQB1 alleles, and also that ethnic origin plays a role in disease susceptibility.