Identification of connective tissue disease autoantibodies and a novel autoantibody anti-annexin A11 in patients with "idiopathic" interstitial lung disease.

BACKGROUND: Autoantibodies are a hallmark feature of Connective Tissue Diseases (CTD). Their presence in patients with idiopathic interstitial lung disease (ILD) may suggest covert CTD. We aimed to determine the prevalence of CTD autoantibodies in patients diagnosed with idiopathic ILD. METHODS: 499 patient sera were analysed: 251 idiopathic pulmonary fibrosis (IPF), 206 idiopathic non-specific interstitial pneumonia (iNSIP) and 42 cryptogenic organising pneumonia (COP). Autoantibody status was determined by immunoprecipitation. RESULTS: 2.4% of IPF sera had a CTD-autoantibody compared to 10.2% of iNSIP and 7.3% of COP. 45% of autoantibodies were anti-synthetases. A novel autoantibody targeting an unknown 56 kDa protein was found in seven IPF patients (2.8%) and two NSIP (1%) patients. This was characterised as anti-annexin A11. CONCLUSION: Specific guidance on autoantibody testing and interpretation in patients with ILD could improve diagnostic accuracy. Further work is required to determine the clinical significance of anti-annexin A11.

Agreement between local and central anti-synthetase antibodies detection: results from the Classification Criteria of Anti-Synthetase Syndrome project biobank.

OBJECTIVES: The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an "ad-interim" study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity. METHODS: We collected 787 serum samples from participating centres for the CLASS project and their local anti-ARS test results. These samples underwent initial central testing using RNA-IP. Following this, the specificity of ARS was reconfirmed centrally through ELISA, line-blot assay (LIA), and, in cases of conflicting results, protein-IP. The sensitivity, specificity, positive likelihood ratio and positive and negative predictive values were evaluated. We also calculated the inter-rater agreement between central and local results using a weighted κ co-efficient. RESULTS: Our analysis demonstrates that local, real-world detection of anti-Jo1 is reliable with high sensitivity and specificity with a very good level of agreement with our central definition of anti-Jo1 antibody positivity. However, the agreement between local immunoassay and central determination of anti-non-Jo1 antibodies varied, especially among results obtained using local LIA, ELISA and "other" methods. CONCLUSIONS: Our study evaluates the performance of real-world identification of anti-synthetase antibodies in a large cohort of multi-national patients with ASSD and controls. Our analysis reinforces the reliability of real-world anti-Jo1 detection methods. In contrast, challenges persist for anti-non-Jo1 identification, particularly anti-PL7 and rarer antibodies such as anti-OJ/KS. Clinicians should exercise caution when interpreting anti-synthetase antibodies, especially when commercial immunoassays test positive for non-anti-Jo1 antibodies.

Assessing the sensitivity and specificity of myositis-specific and associated autoantibodies: a sub-study from the MyoCite cohort.

OBJECTIVES: Myositis-specific and associated autoantibodies are important biomarkers in routine clinical use. We assessed local testing performance for myositis autoantibodies by comparing line immunoassay (LIA) to protein radio-immunoprecipitation and identifying clinical characteristics associated with each myositis autoantibody in the MyoCite cohort. METHODS: Serum samples from patients within the MyoCite cohort, a well-characterised retro-prospective dataset of adult and juvenile idiopathic inflammatory myopathy (IIM) patients in Lucknow, India (2017-2020), underwent LIA at Sanjay Gandhi Postgraduate Institute of Medical Science (SGPGIMS), Lucknow. Immunoprecipitation of 147 IIM patient serum samples (125 adult-onset, 22 juvenile-onset) was conducted at the University of Bath, with researchers blind to LIA results. LIA performance was assessed against Immunoprecipitation as the reference standard, measuring sensitivity, specificity, and inter-rater agreement. Univariate and multivariate logistic regression determined clinical associations for specific MSA. RESULTS: Immunoprecipitation identified myositis autoantibodies in 56.5% (n = 83) of patient samples, with anti-Jo1 (n = 16; 10.9%) as the most common, followed by anti-MDA5 (n = 14, 9.5%). While LIA showed good agreement for anti-Jo1, anti-PL7 and anti-PL12 (Cohen's κ 0.79, 0.83, and 1, respectively), poor agreement was observed in other subgroups, notably anti-TIF1γ (Cohen's κ 0.21). Strongly positive samples, especially in myositis-specific autoantibodies, correlated more with immunoprecipitation results. Overall, 59 (40.1%) samples exhibited non-congruence on LIA and Immunoprecipitation, and κ values for LIA's for anti-TIF1γ, anti-Ku, anti-PmScl, anti-Mi2, and anti-SAE ranged between 0.21-0.60. CONCLUSION: While LIA reliably detected anti-Jo1, anti-PL7, anti-PL12, anti-MDA5, and anti-NXP-2, it also displayed false positives and negatives. Its effectiveness in detecting other autoantibodies, such as anti-TIF1γ, was poor.

The use of ELISA is comparable to immunoprecipitation in the detection of selected myositis-specific autoantibodies in a European population.

Background: The reliable detection of myositis-specific autoantibodies (MSA) provides valuable clinical information regarding prognosis, clinical progression and diagnostic confirmation. Objectives: To evaluate the reliability of a commercial ELISA immunoassay in detecting myositis-specific autoantibodies in comparison to immunoprecipitation as the reference standard. Methods: Serum samples were chosen from a biobank of more than 3000 samples. Samples with a confirmed MSA on Immunoprecipitation (n=116) were evaluated in duplicate by ELISA to detect Mi2, MDA5, Jo1, EJ, KS, PL-7 and PL-12 (Medical & Biological Laboratories Co. Ltd, Nagoya, Aichi, Japan). Healthy control samples (n=246) confirmed autoantibody negative by immunoprecipitation were similarly assessed. Results: There was a very good agreement between ELISA and immunoprecipitation for serum samples containing anti-Mi2, MDA5, Jo1, EJ, KS and PL-7 and PL-12 auto-antibodies. Cohen's κ values ranged from 0.86-1 for the measured autoantibodies on ELISA. Conclusion: ELISA was an accurate method for detecting anti-synthetase, anti-Mi2 and anti-MDA5 autoantibodies.

Representation Rate and Management of Gout for Patients Discharged From Emergency Departments in Illawarra Shoalhaven Local Health District.

Introduction: The estimated prevalence of gout in Western societies is 2.7% to 6.7%. In Australia, there have been increasing rates of hospitalisations for gout flares. Urate-lowering therapy (ULT) is effective in reducing urate burden, which can prevent gout flares and destructive arthropathy. This study assessed the representation rate of patients presenting to the Emergency Department (ED) with crystal arthropathy and the utilisation of ULT in the community for patients with a pre-existing history of gout. Methods: A retrospective review of electronic records of patients presenting to the ED from the Illawarra Shoalhaven Local Health District was performed. Patients included were coded as per the 10th revision of the International Classification of Diseases coding for crystal arthropathy. Results: In all, 18.8% of all crystal arthropathy encounters to the ED were repeat presentations. Of the 70% of patients with a history of gout, only 30.8% were on ULT. Discussion: Despite evidence-based recommendations for a 'treat-to-target' approach, most patients with a previous history of gout were not on ULT. One in five encounters were re-presentations for crystal arthropathy. Effective adherence to treatment guidelines may reduce the number of repeat encounters for gout flare in the ED.

Systematic review and meta-analysis on prevalence of metabolic syndrome in psoriatic arthritis, rheumatoid arthritis and psoriasis.

BACKGROUND: Psoriatic arthritis (PsA), rheumatoid arthritis (RA) and psoriasis (PsO) are associated with systemic inflammation and increased cardiovascular mortality and morbidity. Metabolic syndrome (MetS) is associated with systemic inflammation, and conditions associated with MetS, such as obesity, are associated with difficulty in attaining minimal disease activity (MDA) in individuals with inflammatory arthritis. This systematic review aims to determine whether there is an increased prevalence of MetS in PsA populations compared with PsO and RA populations. METHODS: A systematic review was conducted to assess the prevalence of MetS in PsA, PsO, and RA populations following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The quality of the studies reviewed was assessed using the Joanna Briggs Institute Checklist for Prevalence Studies. RESULTS: The pooled prevalence of MetS in PsA populations was 0.46 ± 0.06 (95% CI 0.40-0.51). In comparison, the prevalence of MetS in PsO and RA populations was 0.34 ± 0.03 (95% CI 0.32-0.37) and 0.31 ± 0.04 (95% CI 0.27-0.35), respectively. Patients with PsA were 1.62 ± 0.036 (95% CI 1.50-1.74) and 1.66 ± 0.038 (95% CI 1.54-1.79) times more likely to have MetS compared with PsO and RA populations. CONCLUSION: The prevalence of MetS is significantly increased in PsA populations compared with PsO and RA populations. Further studies should be performed using a standardized definition of MetS in PsA, RA, and PsO populations to determine whether addressing the metabolic components in MetS offers any therapeutic benefits and in terms of attaining MDA and improving cardiovascular health.