A Novel Pool of Microparticle Cholesterol Is Elevated in Rheumatoid Arthritis but Not in Systemic Lupus Erythematosus Patients.

Microparticles are sub-micron, membrane-bound particles released from virtually all cells and which are present in the circulation. In several autoimmune disorders their amount and composition in the circulation is altered. Microparticle surface protein expression has been explored as a differentiating tool in autoimmune disorders where the clinical pictures can overlap. Here, we examine the utility of a novel lipid-based marker-microparticle cholesterol, present in all microparticles regardless of cellular origin-to distinguish between rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We first isolated a series of microparticle containing lipoprotein deficient fractions from patient and control plasma. There were no significant differences in the size, structure or protein content of microparticles isolated from each group. Compared to controls, both patient groups contained significantly greater amounts of platelet and endothelial cell-derived microparticles. The cholesterol content of microparticle fractions isolated from RA patients was significantly greater than those from either SLE patients or healthy controls. Our data indicate that circulating non-lipoprotein microparticle cholesterol, which may account for 1-2% of measured cholesterol in patient samples, may represent a novel differentiator of disease, which is independent of cellular origin.

Elevated CRP even at the first visit to a rheumatologist is associated with long-term poor outcomes in patients with psoriatic arthritis.

OBJECTIVES: Little is known about the long-term association of CRP levels during psoriatic arthritis (PsA) disease course. In this study, we examined whether raised CRP over the disease course is associated with worse outcome measures in a well-characterised PsA cohort with a long-term follow up. METHODS: A cohort of 283 PsA patients (fulfilling CASPAR criteria) was evaluated. All underwent detailed skin and rheumatologic assessments. Moreover, we documented the presence/absence of comorbidities using Charlson Comorbidity Index (CCI). CRP at first visit to a rheumatologist was documented. Cumulative inflammation over time was represented by the cumulative averages of CRP (ca-CRP). Multiple linear regression modelling CRP was used. RESULTS: Two hundred eighty-three PsA patients attended for detailed assessments. A total of 56.5% (n = 160) of the cohort had raised CRP at their first visit to our rheumatology department, and this was significantly associated with long-term erosions, sacroiliitis, PsA requiring TNFi, and high comorbidity Index, on logistic regression analysis. Moreover, 24% (n = 69) of the cohort never had raised CRP during their long-term follow-up, and on logistic regression analysis, such patients had significantly milder disease with fewer erosions, less sacroiliitis and fewer patients requiring TNFi therapy. The median (IQR) and mean (SD) Ca-CRP was 8.8 (4.6-14.8) and 11.72 (10.52), respectively. On multiple linear regression, erosions, sacroiliitis and CCI were most significantly associated with ca-CRP [(F = 77.6, p < 0.001), 72% (R-square)]. CONCLUSIONS: Elevated CRP is associated with radiographic damage, disease more resistant to treatment and also having higher number of significant comorbidities. Raised CRP can help stratify patients with a more severe PsA phenotype. Key Points • Raised CRP can provide important future prognostic information among patients with PsA. • PsA patients with raised CRP at first visit to a rheumatologist had significantly more destructive and refractory disease. • PsA patients with consistently normal CRP had significantly milder disease.

Inflammatory back pain in psoriatic arthritis is significantly more responsive to corticosteroids compared to back pain in ankylosing spondylitis: a prospective, open-labelled, controlled pilot study.

BACKGROUND: The efficacy of corticosteroids in patients with psoriatic arthritis (PsA) and inflammatory back pain has not been studied to date. In this controlled trial, we aimed to investigate the comparative performance of corticosteroids in patients with active axial-PsA (AxPsA) versus those with active ankylosing spondylitis (AS). METHODS: Patients with AxPsA and AS (naïve to biologic therapies), who not only had clinically active disease, but also had bone marrow oedema on magnetic resonance imaging of the sacroiliac joints, were recruited. Clinically active disease was defined as inflammatory back pain (fulfilling Assessment of Spondyloarthritis International Society (ASAS) expert criteria), with spinal pain score (numerical rating scale 0-10) ≥4 and Bath AS Disease Activity Index (BASDAI) score ≥4 despite taking nonsteroidal anti-inflammatory drugs. Moreover, we recruited a control group of patients with non-inflammatory lower back pain. All patients received a single, intra-muscular dose of depot corticosteroid injection (triamcinolone acetonide 80 mg) at baseline. The intra-muscular corticosteroid option was used to overcome any drug compliance issues. Clinical outcome assessments were made at the following time points: baseline, week 2, and week 4. The primary efficacy end point was mean change in Ankylosing Spondylitis Disease Activity Score (ASDAS) at week 2. Key secondary outcomes were mean change in the BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI) and Ankylosing Spondylitis Quality of Life (ASQoL) at weeks 2 and 4. RESULTS: In total, 40 patients were recruited (15 with AxPsA, 15 with AS, and 10 controls). At week 2 following corticosteroid treatment, patients with AxPsA had significantly greater improvement in the mean ASDAS compared to patients with AS (1.43 ± 0.39 vs. 1.03 ± 0.30, p = 0.004), and also when compared to controls (p < 0.001). At week-4, similar significant trend of ASDAS improvement was seen among AxPsA patients compared to AS patients (1.09 ± 0.32 vs. 0.77 ± 0.27, p = 0.007) and controls (p < 0.001). Similarly, the mean BASDAI, visual analogue scale spinal pain score, ASQoL and BASFI improved significantly among patients with AxPsA compared to patients with AS and controls at week 2 (p < 0.05), with this trend also largely maintained at week 4. CONCLUSIONS: Axial inflammation in patients with PsA responds significantly better to corticosteroids than in patients with AS. This furthers the argument and adds to the growing evidence that AxPsA and AS are distinct entities.