Autoantibodies against the NineTeen complex and U5 RNP in systemic sclerosis.

ObjectiveMultiple spliceosome components are known autoantigens in systemic sclerosis (SSc). Here we aim to identify new and characterize rare anti-spliceosomal autoantibodies in patients with SSc without known autoantibody specificity. MethodsSera that precipitated spliceosome subcomplexes, as detected by immunoprecipitation-mass spectrometry (IP-MS), were identified from a database of 106 patients with SSc without known autoantibody specificity. New autoantibody specificities were confirmed with immunoprecipitation-western blot. The IP-MS pattern of new anti-spliceosomal autoantibodies was compared with anti-U1 RNP-positive sera of patients with different systemic autoimmune rheumatic diseases and anti-SmD-positive sera of patients with systemic lupus erythematosus (n = 24). ResultsThe NineTeen Complex (NTC) was identified and confirmed as new spliceosomal autoantigen in one patient with SSc. U5 RNP, as well as additional splicing factors, were precipitated by the serum of another patient with SSc. The IP-MS patterns of anti-NTC and anti-U5 RNP autoantibodies were distinct from those of anti-U1 RNP- and anti-SmD-positive sera. Furthermore, there was no difference in IP-MS patterns between a limited number of anti-U1 RNP-positive sera of patients with different systemic autoimmune rheumatic diseases. ConclusionAnti-NTC autoantibodies are a new anti-spliceosomal autoantibody specificity, here first identified in a patient with SSc. Anti-U5 RNP autoantibodies are a distinct but rare anti-spliceosomal autoantibody specificity. All major spliceosomal subcomplexes have now been described as target of autoantibodies in systemic autoimmune diseases.

Identification of new telomere- and telomerase-associated autoantigens in systemic sclerosis.

PURPOSE: In up to 20% of patients with systemic sclerosis (SSc) no known autoantibody specificity can be identified. Recently discovered autoantigens, such as telomeric repeat binding factor 1 (TERF1), as well as established autoantigens, like RuvBL1/2, are associated with telomere and telomerase biology. We aimed to identify new telomere- and telomerase-associated autoantigens in patients with SSc without known autoantibody specificity. METHODS: Unlabelled protein immunoprecipitation combined with gel-free liquid chromatography-tandem mass spectrometry (IP-MS) was performed with sera of 106 patients with SSc from two tertiary referral centres that had a nuclear pattern on HEp-2 indirect immunofluorescence without previously identified autoantibody. Telomere- or telomerase-associated proteins or protein complexes precipitated by individual sera were identified. Candidate autoantigens were confirmed through immunoprecipitation-western blot (IP-WB). A custom Luminex xMAP assay for 5 proteins was evaluated with sera from persons with SSc (n = 467), other systemic autoimmune rheumatic diseases (n = 923), non-rheumatic disease controls (n = 187) and healthy controls (n = 199). RESULTS: Eight telomere- and telomerase-associated autoantigens were identified in a total of 11 index patients, including the THO complex (n = 3, all with interstitial lung disease and two with cardiac involvement), telomeric repeat-binding factor 2 (TERF2, n = 1), homeobox-containing protein 1 (HMBOX1, n = 2), regulator of chromosome condensation 1 (RCC1, n = 1), nucleolar and coiled-body phosphoprotein 1 (NOLC1, n = 1), dyskerin (DKC1, n = 1), probable 28S rRNA (cytosine(4447)-C(5))-methyltransferase (NOP2, n = 1) and nuclear valosin-containing protein-like (NVL, n = 2). A Luminex xMAP assay for THO complex subunit 1 (THOC1), TERF2, NOLC1, NOP2 and NVL revealed high reactivity in all index patients, but also in other patients with SSc and disease controls. However, the reactivity by xMAP assay in these other patients was not confirmed by IP-WB. CONCLUSION: IP-MS revealed key telomere- and telomerase-associated proteins and protein complexes as autoantigens in patients with SSc.

Treat-to-target in rheumatoid arthritis: a real-world study of the application and impact of treat-to-target within the wider context of patient management, patient centricity and advanced therapy use in Europe.

BACKGROUND: While treat-to-target (T2T) is endorsed for the management of rheumatoid arthritis (RA), data on the degree of implementation in clinical practice are limited. This study investigated the use of T2T for RA in a real-world setting across Europe. METHODS: The Adelphi RA Disease-Specific Programme was a point-in-time survey of rheumatologists and their consulting patients with RA conducted between January and October 2020 in Belgium, France, Germany, Italy, Spain and the UK. Rheumatologists completed an attitudinal survey, and a record form for their next 10-12 consulting patients, who were invited to voluntarily complete a patient-reported questionnaire. Data collected included clinical characteristics, treatment patterns and attitudes towards T2T. RESULTS: Overall, 316 rheumatologists provided data for 3120 patients, of whom 1108 completed the questionnaire. While 86.1% of rheumatologists estimated using T2T principles in clinical practice, only 66.6% of patients were reported by their physician to be managed using a T2T approach. Achieving disease remission was the most commonly reported treatment goal identified by rheumatologists (79.7%), followed by symptom control (47.8%) and reducing impact on quality of life (44.5%). 40.8% of rheumatologists and their patients were in agreement that a treatment goal had been set. When there was agreement on treatment goals, we observed better patient satisfaction, engagement and treatment success. CONCLUSIONS: Despite recommendations, the T2T approach in RA appears to be suboptimally implemented in clinical practice. This highlights the importance of patient-centricity in the decision-making process to define meaningful targets and select appropriate treatments to improve disease outcomes.

Standardised interpretation of capillaroscopy in autoimmune idiopathic inflammatory myopathies: A structured review on behalf of the EULAR study group on microcirculation in Rheumatic Diseases.

OBJECTIVE: We conducted a systematic review, on behalf of the EULAR Study Group on Microcirculation in Rheumatic Diseases (EULAR SG MC/RD), to investigate the value of nailfold videocapillaroscopy (NVC) in idiopathic inflammatory myopathies (IIM). METHODS: Three electronic databases were systematically searched to find all relevant manuscripts reporting NVC outcomes in IIM patients. Articles were assessed based on study design, population, NVC methodology and description of NVC results. To allow comparison between the articles, all NVC results were interpreted according to standardised capillaroscopic terminology, as previously consented by the EULAR SG MC/RD and the Scleroderma Clinical Trials Consortium (SCTC) Group on Capillaroscopy. RESULTS: Of the 653 identified records; five were retained after critical appraisal on title, abstract and manuscript level. A marked difference in NVC was observed between (juvenile) dermatomyositis [(j)DM] versus polymyositis, healthy controls and systemic sclerosis patients. In addition, reduced capillary density and scleroderma pattern seem to be associated with active disease in (j)DM, while immunosuppressive treatment appears to reduce NVC abnormalities. CONCLUSION: This is the first systematic review investigating NVC in IIM, interpreting the results according to an international consented standardised manner, as proposed by the EULAR SG MC/RD and SCTC Group on Capillaroscopy. We can conclude that NVC presents a promising asset in the diagnosis of (j)DM. Moreover, NVC could be a biomarker for organ involvement and follow-up. Large multicentre prospective standardised studies are further needed to definitely describe associations with clinical and laboratory parameters in the different IIM subtypes.

Off-label use of mycophenolate mofetil in the treatment of rare and complex rheumatic connective tissue diseases.

OBJECTIVES: We aimed to investigate the clinical off-label use of mycophenolate mofetil (MMF), including its safety and efficacy in patients with rare and complex rheumatic connective tissue diseases (rCTDs). METHODS: A survey was distributed across experts from ERN-ReCONNET reference centres in order to assess the experience with MMF off-label use. Patient-level data of patients with rCTDs under treatment with MMF was also collected for analysis of safety and efficacy. RESULTS: Twelve experts from eleven centres distributed throughout Europe (7 countries) answered the survey. The experience was concordant in that, despite of its off-label use, experts reported opting frequently for this therapeutic alternative with robust confidence on its efficacy and safety. The analysis of 108 patients with rCTDs under MMF revealed a good safety profile, as well as good clinical outcomes, especially for systemic lupus erythematosus and idiopathic inflammatory myopathies. The presence of interstitial lung disease was, as expected, associated with a worse clinical outcome despite use of MMF. CONCLUSIONS: MMF is widely used in reference centres for rCTDs. Its safety profile and efficacy seem to be recognised by experts and demonstrated with patient-level analysis. While selected rCTDs will likely remain an off-label indication for MMF, robust data seem to support this therapy as an appropriate alternative for safely and effectively treating many manifestations of rCTDs.

Positioning of myositis-specific and associated autoantibody (MSA/MAA) testing in disease criteria and routine diagnostic work-up.

Nowadays, the importance of detection of myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) in diagnosis and in delineating disease subsets of idiopathic inflammatory myopathy (IIM) is highly acknowledged by IIM experts. Consequently, MSA/MAA are increasingly integrated in expert-based myositis (sub)classification criteria as well as in routine diagnostics. In contrast, MSA/MAA are under-represented in data-based (sub)classification criteria, mostly related to the lack of sufficient data on the wide spectrum of MSA/MAA in large multicenter cohorts. Unfortunately, the current commercially available assays to detect MSA/MAA show variable analytical and clinical performance characteristics. This challenges the design of prospective multicenter studies on MSA/MAA as well as the optimization of their routine clinical use. Additional validation studies and continuous harmonization initiatives on MSA/MAA detection from the pre-analytical to the post-analytical phase (e.g. from defining request criteria to guidelines for reporting), will be needed to overcome these hurdles. To speed up this process, we encourage close collaborations between IIM clinical experts, laboratory professionals and diagnostic companies.

Clinical spectrum time course in non-Asian patients positive for anti-MDA5 antibodies.

OBJECTIVES: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. METHODS: We conducted a multicentre, international, retrospective cohort study. RESULTS: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. CONCLUSIONS: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Incidence, prevalence and long-term progression of Goh algorithm rated interstitial lung disease in systemic sclerosis in two independent cohorts in flanders: A retrospective cohort study.

OBJECTIVES: The epidemiology of interstitial lung disease (ILD) in systemic sclerosis (SSc) in Belgium is unknown. In literature, its prevalence varies between 19% and 52% in limited/diffuse cutaneous SSc (LcSSc/DcSSc). However, its prevalence in "early" SSc (pre-clinically overt SSc without [yet] skin involvement), nor its incidence rate in SSc (LcSSc/DcSSc/"early" SSc) has ever been described. Against this background, we aimed to determine the prevalence/incidence (rate) and progression of ILD in SSc. METHODS: 12-year follow-up data of consecutive SSc patients, included in two Flemish cohorts (University Hospitals Ghent and Leuven), were retrospectively analysed. ILD was classified according to the simplified Goh algorithm. Progression of ILD was defined as a relative decline of FVC ≥10%, a combined relative decline of FVC 5-10% and DLCO ≥15%, or as an increase in HRCT extent. RESULTS: 722 patients (60% LcSSc/ 20% DcSSc/ 20% "early" SSc, median (IQR) follow-up 39 [12-80] months) had baseline HRCT. 243 were rated to have ILD at baseline and 39 during follow-up (prevalence of 34%/ incidence rate of 20.3/1000PY, 95%CI:14.5-27.8). Amongst those with baseline ILD, 60% had lung functional progression at five years of follow-up. In the "early" SSc subgroup, eight patients were rated to have ILD at baseline and three during follow-up (prevalence of 6%/ incidence rate of 5.8/1000 PY, 95%CI:1.2-17.0). CONCLUSION: Both LcSSc and DcSSc patients should be monitored for ILD evolution. The low prevalence and incidence of ILD in the "early" SSc subgroup may instruct future decisions on the construction of uniform patient follow-up pathways in "early" SSc.

Pitfalls in the detection of myositis specific antibodies by lineblot in clinically suspected idiopathic inflammatory myopathy.

OBJECTIVES: Today, the contribution of myositis-specific autoantibodies (MSA) in the diagnostic workup of idiopathic inflammatory myopathies (IIM) is on the rise. The aim of this study was to document MSA frequency as detected by lineblot in a set of consecutive MSA requests and to correlate the results with clinical diagnosis, IIM subtype and indirect immunofluorescence (IIF) findings. Additionally, a comparison between two lineblots was performed. METHODS: A total of 118 consecutive samples of patients with suspicion of IIM were analysed on IIF and two lineblots. A total of 107 patients with autoimmune rheumatic diseases served as controls. RESULTS: MSA were detected in 55% of IIM patients (n=31) and 7.9% (n=12) of patients without clinical diagnosis of IIM or myositis overlap syndrome. All the IIM patients had a MSA-compatible clinical subtype. There was no to fair agreement between both lineblots for the individual antibodies, with most discrepancies observed for anti-TIF1γ (κ=-0.021), anti-SRP (κ=-0.006) and anti-SAE (κ=0.395). Differences between both assays were mostly observed in the non-IIM patients, also showing signi cantly lower blot signal intensities compared to IIM patients (p=0.0013). MSA in the non-IIM patients frequently showed an incompatible IIF pattern. CONCLUSIONS: Lineblot seems to be an interesting tool for MSA detection in a clinical context, allowing the identification of clinical subtypes. However, considerable caution must be exercised in interpreting the results in case of low positive MSA signal intensity, discordant lineblot results and/or an incompatible IIF pattern.

RORγt inhibition selectively targets IL-17 producing iNKT and γδ-T cells enriched in Spondyloarthritis patients.

Dysregulated IL-23/IL-17 responses have been linked to psoriatic arthritis and other forms of spondyloarthritides (SpA). RORγt, the key Thelper17 (Th17) cell transcriptional regulator, is also expressed by subsets of innate-like T cells, including invariant natural killer T (iNKT) and γδ-T cells, but their contribution to SpA is still unclear. Here we describe the presence of particular RORγt+T-betloPLZF- iNKT and γδ-hi T cell subsets in healthy peripheral blood. RORγt+ iNKT and γδ-hi T cells show IL-23 mediated Th17-like immune responses and were clearly enriched within inflamed joints of SpA patients where they act as major IL-17 secretors. SpA derived iNKT and γδ-T cells showed unique and Th17-skewed phenotype and gene expression profiles. Strikingly, RORγt inhibition blocked γδ17 and iNKT17 cell function while selectively sparing IL-22+ subsets. Overall, our findings highlight a unique diversity of human RORγt+ T cells and underscore the potential of RORγt antagonism to modulate aberrant type 17 responses.

Autoantibodies in idiopathic inflammatory myopathies: Clinical associations and laboratory evaluation by mono- and multispecific immunoassays.

Idiopathic inflammatory myopathies (IIM) are a group of diseases characterized by immune-mediated muscular lesions that may be associated with extra-muscular manifestations involving skin, lungs, heart or joints. Four main groups of IIM can be distinguished: dermatomyositis (DM), overlap myositis including mainly anti-synthetase syndrome (ASS), immune mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). Myositis-specific autoantibodies (MSA) are increasingly recognized as valuable tools for diagnosis, classification and prognosis of IIM. For example, ASS is associated with anti-aminoacyl tRNA synthetase antibodies (anti-Jo-1, PL-7, PL-12, …), IMNM with anti-SRP and anti-HMGCR; IBM with anti-cytosolic 5'nucleotidase 1A (cN1A), and DM with anti-Mi-2, anti-MDA-5, anti-TIF-1γ, anti-NXP-2 and anti-SAE. Moreover, anti-MDA-5 is associated with amyopathic myositis and interstitial lung disease and anti-TIF-1γ and anti-NXP-2 with juvenile DM as well as malignancy in patients >40 years. Most MSA have initially been discovered by immunoprecipitation. In routine laboratories, however, MSA are screened for by indirect immunofluorescence and identified by (automated) monospecific immunoassays or by multispecific immunoassays (mainly line/dot immunoassays). Validation of these (multispecific) assays is a challenge as the antibodies are rare and the assays diverse. In this review, we give an overview of the (clinical) performance characteristics of monospecific assays as well as of multispecific assays for detection of MSA. Although most assays are clinically useful, there are differences between techniques and between manufacturers. We discuss that efforts are needed to harmonize and standardize detection of MSA.

A prospective, longitudinal study evaluating the baseline six-minute walk test as an individual reference value in systemic sclerosis patients.

OBJECTIVES: Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are the leading causes of death in systemic sclerosis (SSc). Although the six-minute walk test (6MWT) is used for evaluating ILD and PAH, no data are available on the evolution of the six-minute walk distance (6MWD) in SSc patients without ILD and PAH and whether the baseline 6MWD could serve as individual reference value for the management of those who will develop PAH or ILD. METHODS: Prospectively collected data of the first 6MWT (at baseline or 6-month follow-up) and the 6MWTs at 18-, 30-, 42-, 54-, and 66-month visit of 165 consecutive SSc patients without ILD and PAH, included in the Ghent University SSc Cohort between May 2006 and December 2016 were analysed. RESULTS: 96-100% of the included patients performed a 6MWT during the follow-up visits. The mean 6MWD during the baseline 6MWT of 165 SSc patients without ILD and PAH (35% limited, 56% limited cutaneous, 9% diffuse cutaneous SSc) was 484.20+/-92.65m with no significant difference in the 6MWD at different follow-up visits as compared to baseline. In 46 SSc patients without ILD and PAH who performed a 6MWT at baseline and at 66-month visit, the 6MWD walked at 66-month visit correlated with the baseline 6MWD (r=0.564, p<0.001). CONCLUSIONS: In SSc without ILD and PAH, the 6MWT is feasible and the 6MWD is clinically stable over a 66 months period. Hence, the individual 6MWD might be used as individual reference value in management of those who will develop PAH or ILD.

Is laser speckle contrast analysis (LASCA) the new kid on the block in systemic sclerosis? A systematic literature review and pilot study to evaluate reliability of LASCA to measure peripheral blood perfusion in scleroderma patients.

OBJECTIVES: A reliable tool to evaluate flow is paramount in systemic sclerosis (SSc). We describe herein on the one hand a systematic literature review on the reliability of laser speckle contrast analysis (LASCA) to measure the peripheral blood perfusion (PBP) in SSc and perform an additional pilot study, investigating the intra- and inter-rater reliability of LASCA. METHODS: A systematic search was performed in 3 electronic databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In the pilot study, 30 SSc patients and 30 healthy subjects (HS) underwent LASCA assessment. Intra-rater reliability was assessed by having a first anchor rater performing the measurements at 2 time-points and inter-rater reliability by having the anchor rater and a team of second raters performing the measurements in 15 SSc and 30 HS. The measurements were repeated with a second anchor rater in the other 15 SSc patients, as external validation. RESULTS: Only 1 of the 14 records of interest identified through the systematic search was included in the final analysis. In the additional pilot study: intra-class correlation coefficient (ICC) for intra-rater reliability of the first anchor rater was 0.95 in SSc and 0.93 in HS, the ICC for inter-rater reliability was 0.97 in SSc and 0.93 in HS. Intra- and inter-rater reliability of the second anchor rater was 0.78 and 0.87. CONCLUSIONS: The identified literature regarding the reliability of LASCA measurements reports good to excellent inter-rater agreement. This very pilot study could confirm the reliability of LASCA measurements with good to excellent inter-rater agreement and found additionally good to excellent intra-rater reliability. Furthermore, similar results were found in the external validation.

Association of Inflammatory Bowel Disease and Acute Anterior Uveitis, but Not Psoriasis, With Disease Duration in Patients With Axial Spondyloarthritis: Results From Two Belgian Nationwide Axial Spondyloarthritis Cohorts.

OBJECTIVE: To determine the link between extraarticular manifestations (EAMs) and baseline characteristics in patients with axial spondyloarthritis (SpA), and to define their potentially differential prognostic value in 2 large, independent Belgian axial SpA cohorts with distinct recruitment periods. METHODS: Information on demographic and clinical characteristics and extraarticular manifestations (EAMs) was obtained from patients with axial SpA originating from the (Be)Giant (Belgian Inflammatory Arthritis and Spondylitis) cohort, which includes consecutive axial SpA patients whose data have been collected since 2010, and from the ASPECT (Ankylosing Spondylitis Patients Epidemiological Cross-sectional Trial) cohort, a Belgian registry of cross-sectional data collected between February 2004 and February 2005 from consecutive patients with ankylosing spondylitis (AS) or probable AS. RESULTS: Among the 1,250 Belgian patients studied, disease duration was associated with risk of developing inflammatory bowel disease (IBD), with an increase in risk by 20% per 10 years of disease duration (relative risk [RR] 1.2, P = 0.026), and associated with risk of developing acute anterior uveitis, with an increase in risk by 30% per 10 years of disease duration (RR 1.3, P < 0.001). In the subgroup of 171 newly diagnosed patients with prospective follow-up data, higher mean C-reactive protein levels over time were demonstrated in those with acute anterior uveitis or IBD compared to those without EAMs or those with psoriasis alone (each P = 0.01). CONCLUSION: The risk of developing acute anterior uveitis or IBD, but not psoriasis, in patients with axial SpA seems to increase with disease duration and appears to be linked to a higher cumulative exposure to inflammation, thus providing a possible explanation for the differential structural progression observed in those with axial SpA.

Nailfold capillaroscopy in systemic lupus erythematosus: A systematic review and critical appraisal.

Nailfold capillaroscopy is an easy, non-invasive technique to assess microvascular involvement in rheumatic diseases. Multiple studies describe capillaroscopic changes in systemic lupus erythematosus (SLE), including a wide range of non-specific findings. On behalf of the European League Against Rheumatism (EULAR) study group on microcirculation in rheumatic diseases, a systematic review was done to obtain all original research studies (in English) in which SLE patients had capillaroscopy. Forty such studies are identified. This article firstly provides a résumé of the results of these studies according to capillaroscopic parameters (density, dimensions, morphology, haemorrhages), semi-quantitative assessment and qualitative assessment of capillaroscopy in SLE patients. Secondly, the correlations between capillaroscopic parameters in SLE patients and clinical and laboratory parameters (including auto-immune parameters) are outlined. The following capillaroscopic parameters are found to be significantly more prevalent in SLE patients compared to healthy controls: tortuous capillaries, abnormal morphology and haemorrhages. Hairpin-shaped capillaries are significantly less prevalent than in healthy persons. The semi-quantitatively determined nailfold capillaroscopic score (NFC score) in SLE patients is also higher than in healthy controls. Several correlations between clinical and laboratory parameters and capillaroscopic parameters are identified in the review. Disease activity is correlated with NFC score in seven studies, with abnormal morphology (i.e. "meandering") in one study and with haemorrhages in one study. Frequent attacks of Raynaud's phenomenon (RP) and gangrene are significantly correlated with dilated capillaries. In two studies a possible correlation between anti-SSA antibodies and lower density of capillaries is withheld. About other immune parameters conflicting results are found. In one study a significant negative correlation is found between 24-hour proteinuria and abnormal morphology (i.e. "meandering"). For the first time, an overview of the nailfold capillaroscopic changes that have been described in SLE and their correlations with clinical and laboratory findings is given. Further large-scale research on the identification of capillaroscopic changes in SLE and their correlations with standardised clinical and laboratory parameters, is ongoing at the EULAR study group on microcirculation in rheumatic diseases.

The importance of detecting anti-DFS70 in routine clinical practice: comparison of different care settings.

BACKGROUND: Screening for antinuclear antibodies by indirect immunofluorescence (ANA-IIF) is essential in the diagnostic workup of ANA-associated autoimmune rheumatic diseases (AARDs). However, also healthy individuals may test positive, making the interpretation challenging. Recent reports suggest that dense fine speckled 70 antibodies (anti-DFS70) may facilitate this challenge. Here, we investigate their clinical importance based on data from four Belgian laboratories (one primary, two secondary and one tertiary care). METHODS: At least one specific DFS70 assay (DFS70 IgG ELISA or lineblot [Euroimmun, full length antigen] and/or DFS70 IgG CLIA [Inova Diagnostics, truncated antigen]) was performed on four consecutive cohorts of homogeneous-like ANA-IIF samples (n=697). Co-occurrence with AARD-specific ANA and clinical information were documented in the anti-DFS70-positive samples. RESULTS: Using a combination of solid phase techniques, we found between 7.6% and 26% anti-DFS70 in the different cohorts. Focusing on anti-DFS70 CLIA-positive samples without co-occurrence of AARD-specific ANA, we observed a trend towards lower frequency in tertiary (8% [p=0.0786]) and secondary care (12% [p=0.1275] and 6% [p<0.001]) compared to primary care (21%). Moreover, in this specific subpopulation, AARD was less frequent (0%-50% compared to 6%-77% in the total anti-DFS70-positive group). CONCLUSIONS: Anti-DFS70 prevalence depends on the applied assay and care setting. Our data suggest that, for an ANA-IIF-positive patient, it is rather the absence of AARD-associated ANA and clinical symptoms that contribute to the exclusion of AARD than the presence of anti-DFS70. Nevertheless, isolated anti-DFS70 helps to clarify positive ANA-IIF results, especially if pretest probability for AARD is low.

Idiopathic inflammatory myopathies: state of the art on clinical practice guidelines [corrected].

Idiopathic inflammatory myopathies (IIMs) encompass a heterogeneous group of rare autoimmune diseases characterised by muscle weakness and inflammation, but in antisynthetase syndrome arthritis and interstitial lung disease are more frequent and often inaugurate the disease. Clinical practice guidelines (CPGs) have been proposed for IIMs, but they are sparse and heterogeneous. This work aimed at identifying: i) current available CPGs for IIMs, ii) patients ' and clinicians' unmet needs not covered by CPGs. It has been performed in the framework of the European Reference Network on rare and complex connective tissue and musculoskeletal diseases (ReCONNET), a network of centre of expertise and patients funded by the European Union's Health Programme. Fourteen original CPGs were identified, notably recommending that: i) extra-muscular involvements should be assessed; ii) corticosteroids and methotrexate or azathioprine are first-line therapies of IIMs. ii) IVIG is a treatment of resistant-DM that may be also used in other resistant-IIMs; iii) physical therapy and sun protection (in DM patients) are part of the treatment; v) tumour screening for patients with DM include imaging of chest, abdomen, pelvis and breast (in woman) along with colonoscopy (in patients over 50 years); vi) disease activity and damages should be monitor using standardised and validated tools. Yet, only half of these CPGs were evidence-based. Crucial unmet needs were identified both by patients and clinicians. In particular, there was a lack of large multidisciplinary working group and of patients ' preferences. The following fields were not or inappropriately targeted: diagnosis; management of extra-muscular involvements other than skin; co-morbidities and severe manifestations.