Responsiveness of clinical and ultrasound outcome measures in musculoskeletal systemic lupus erythematosus

Objective To assess the responsiveness of clinical outcome measures in musculoskeletal SLE compared with ultrasound. Methods A prospective pilot study was conducted in consecutive SLE patients with inflammatory musculoskeletal symptoms. Clinical assessments including SLEDAI, BILAG, 28-tender and swollen joint counts, physician and patient VAS and ultrasound were performed at 0, 2 and 4 weeks following 120mg intramuscular methylprednisolone acetate. Responsiveness was analysed using changes and effect sizes using Cohen’s criteria. Results 20 patients were recruited. 15/20 had clinical swelling at baseline. All clinical and US parameters were significantly improved at week 4 (all p≤0.01). Musculoskeletal-BILAG score improved in 16/20. Musculoskeletal-SLEDAI improved in 7/20. SRI-4 criteria were assessed in 19 patients with SLEDAI>= 4 at baseline met in 9/19 at 4 weeks. Effect sizes at 4 weeks were large (>0.5) for US, physician VAS and BILAG and medium (>0.3) for joint counts and SLEDAI. Large effect sizes for improvement in US GS and PD were observed in both SRI responders (r=-0.51 and -0.56 respectively) and non-responders (r=-0.62 and -0.59) at 4 weeks. Conclusions This is the first study to measure the responsiveness of clinical outcome measures in musculoskeletal SLE against an objective inflammation measure. BILAG and physician VAS were the most responsive clinical instruments. US was highly responsive in musculoskeletal SLE, while SLEDAI and joint counts appeared suboptimal for detection of improvement. These results suggest that clinical trials based on the SLEDAI and SRI-4 may underestimate the efficacy of therapy in SL

Autoantibodies to posttranslational modifications in rheumatoid arthritis

Autoantibodies have been associated with human pathologies for a long time, particularly with autoimmune diseases (AIDs). Rheumatoid factor (RF) is known since the late 1930s to be associated with rheumatoid arthritis (RA). The discovery of anticitrullinated protein antibodies in the last century has changed this and other posttranslational modifications (PTM) relevant to RA have since been described. Such PTM introduce neoepitopes in proteins that can generate novel autoantibody specificities. The recent recognition of these novel specificities in RA provides a unique opportunity to understand human B-cell development in vivo. In this paper, we will review the three of the main classes of PTMs already associated with RA: citrullination, carbamylation, and oxidation. With the advancement of research methodologies it should be expected that other autoantibodies against PTM proteins could be discovered in patients with autoimmune diseases. Many of such autoantibodies may provide significant biomarker potential

Gut microbiota functions: metabolism of nutrients and other food components

The diverse microbial community that inhabits the human gut has an extensive metabolic repertoire that is distinct from, but complements the activity of mammalian enzymes in the liver and gut mucosa and includes functions essential for host digestion. As such, the gut microbiota is a key factor in shaping the biochemical profile of the diet and, therefore, its impact on host health and disease. The important role that the gut microbiota appears to play in human metabolism and health has stimulated research into the identification of specific microorganisms involved in different processes, and the elucidation of metabolic pathways, particularly those associated with metabolism of dietary components and some host-generated substances. In the first part of the review, we discuss the main gut microorganisms, particularly bacteria, and microbial pathways associated with the metabolism of dietary carbohydrates (to short chain fatty acids and gases), proteins, plant polyphenols, bile acids, and vitamins. The second part of the review focuses on the methodologies, existing and novel, that can be employed to explore gut microbial pathways of metabolism. These include mathematical models, omics techniques, isolated microbes, and enzyme assays

The role of ultrasound in assessing musculoskeletal symptoms of systemic lupus erythematosus: a systematic literature review.

Objectives. Musculoskeletal symptoms are common in SLE and are associated with significant morbidity. However, assessing their nature can be challenging, with implications for treatment decisions and measuring response. US has been shown to be valid and reliable for the assessment of other inflammatory arthritides, but data in SLE are more limited. The objectives of this systematic literature review were to determine the characteristics of musculoskeletal US abnormalities in SLE and to evaluate the metric properties of US in the detection and quantification of musculoskeletal symptoms. Methods. We systematically searched the literature using the PubMed, Embase and Cochrane Library databases for studies using musculoskeletal US for assessing SLE. Studies were assessed for quality using the Quality Assessment of Diagnostic Accuracy Studies tool and for their metric qualities, including reliability and validity. Results. Nine studies were identified. Most studies investigated construct validity. Rates of abnormality were highly variable: synovitis and tenosynovitis were reported in 25–94% and 28–65% of patients, respectively; power Doppler and erosions were reported in 10–82% and 2–41% of patients, respectively. There was poor to moderate association between US abnormalities and disease activity indices and immunological findings. There was moderate to high risk of bias and there were concerns about applicability in most studies. Conclusion. US has potential value in the assessment of musculoskeletal symptoms in SLE. However, there is methodological variation between studies that may account for lack of consensus on US abnormalities. Studies that address these problems are required before US can used as an outcome measure in SLE

Development and Validation of the OMERACT Rheumatoid Arthritis Magnetic Resonance Tenosynovitis Scoring System in a Multireader Exercise

Objective. To develop and validate a magnetic resonance imaging (MRI) tenosynovitis (TS) score for tendons at the wrist and metacarpophalangeal (MCP) joint levels in patients with rheumatoid arthritis (RA). Methods. Axial T1-weighted precontrast and postcontrast fat-saturated MR image sets of the hands of 43 patients with RA initiating rituximab therapy were obtained at baseline and after 14, 26, 38, or 52 weeks. The MR images were scored twice by 4 readers. Nine tendon compartments of the wrist and 4 flexor tendon compartments at the MCP joints were assessed. Tenosynovitis was scored as follows: 0: No; 1: < 1.5 mm; 2: ≥ 1.5 mm but < 3 mm; 3: ≥ 3 mm peritendinous effusion and/or postcontrast enhancement. Intrareader and interreader intraclass correlation coefficients (ICC), smallest detectable change (SDC), percentage of exact and close agreement (PEA/PCA), and standardized response mean (SRM) were calculated. Results. Intrareader and interreader ICC for status and change scores were very good (≥ 0.80) for total scores for all readers. Intrareader SDC was ≤ 3.0 and interreader SDC was < 2.0. The overall PEA/PCA intrareader and interreader agreements for change scores in all tendons were 73.8%/97.6% and 47.9%/85.0%, respectively. Average SRM was moderate for total scores and 60.5% of the patients had a tenosynovitis change score ≥ SDC. Conclusion. The TS score showed high intrareader and interreader agreement for wrist and finger tendons, with moderate responsiveness, and the majority of the patients showed a change above the SDC. This scoring system may be included as a component of the RAMRIS