Andrea Cuervo

Serum Calprotectin Versus Acute-Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors

To compare the accuracy of serum calprotectin and acute‐phase reactants (C‐reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) in stratifying disease activity in rheumatoid arthritis (RA) patients receiving tumor necrosis factor inhibitors (TNFi), and to correlate calprotectin levels with TNFi trough serum levels.

Immunopathologic characterization of ultrasound-defined synovitis in rheumatoid arthritis patients in clinical remission

BackgroundPatients with rheumatoid arthritis (RA) in clinical remission may have ultrasound-defined synovitis according to the presence of power Doppler (PD) signal. The objective was to describe the immunopathologic characteristics of ultrasound-defined synovitis compared with synovitis in patients with clinically active RA.MethodsWe included between 6 and 8 ultrasound-guided synovial biopsies per patient from 20 patients with RA in clinical remission (DAS28-ESR <2.6) with PD signal, 22 synovial tissue samples (ST) from patients with clinically active RA (swollen joint with confirmed inflammatory synovial fluid) as inflammatory controls, and 10 ST from non-inflammatory controls. Immunostaining for CD3 (T lymphocytes), CD20 (B lymphocytes), CD68 (macrophages), CD117 (mast cells), hsp47 (fibroblasts), bFGF and CXCL12 (angiogenic factors) was made and quantified by digital image analysis. The number of CD31 vessels/mm2 was quantified.ResultsRA patients in remission with PD signal had significantly reduced synovial T-cell, B-cell, mast cell and fibroblast density, but similar macrophage infiltration compared with patients with clinically active RA. Vascularity, bFGF and CXCL12 were partially reduced in RA patients in remission with PD signal compared to those with active RA, but were significantly higher compared with ST from non-inflammatory controls. During the 12-month follow up, 8/20 RA patients (40 %) lost remission: all had synovial hypertrophy grade ≥2 and significantly more synovial B cells and mast cells than patients maintaining remission.ConclusionsAsymptomatic ultrasound-defined synovitis and clinically active arthritis differ in the degree of infiltrating lymphoid, mast cells and fibroblast density, but are similar with respect to macrophage infiltration. Persistently increased angiogenic factor expression and vascularity may explain the persistence of a PD signal.

Serum Calprotectin More Accurately Discriminates the Inflammatory Disease Activity of Rheumatoid Arthritis Patients Receiving TNF inhibitors than Acute Phase Reactants

To compare the accuracy of serum calprotectin and acute‐phase reactants (C‐reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) in stratifying disease activity in rheumatoid arthritis (RA) patients receiving tumor necrosis factor inhibitors (TNFi), and to correlate calprotectin levels with TNFi trough serum levels.

Clinical and sonographic biomarkers of structural damage progression in RA patients in clinical remission: A prospective study with 12 months follow-up

OBJECTIVE To determine clinical and sonographic biomarkers predicting structural damage progression at 12 months of follow-up as measured by magnetic resonance imaging (MRI) in rheumatoid arthritis (RA) patients in clinical remission. PATIENTS AND METHODS We included patients with RA in clinical remission, defined as 28-joint disease activity score (DAS28)-erythrocyte sedimentation rate (ESR) <2.6 for >6 months. Ultrasound scans of both hands and knees and MRI of the dominant hand were performed at baseline and at 12 months. RESULTS Out of 55 patients, 42 completed the follow-up. Among them, 78% were female, aged (median) 54 years; disease duration was 93 months. In total, 12 (28%) patients were taking oral prednisone, 34 (81%) conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 20 (47%) biological therapies. At baseline, 45% fulfilled criteria previously defined for ultrasound-defined active synovitis (UdAS) [PD (power Doppler) signal + synovial hyperplasia ≥2]. Multivariate analysis showed significant associations between baseline MRI erosion score, body mass index (BMI), disease duration, prednisone treatment, absence of biologic and csDMARDs, UdAS, and MRI erosion score progression after 12 months. In an exploratory analysis, serum levels of calprotectin correlated significantly with bone edema progression. CONCLUSIONS We identified clinical and sonographic markers of structural damage progression after 12 months follow-up in patients with RA in clinical remission. Meeting the criteria of ultrasound active synovitis, defined as simultaneous relevant synovial hyperplasia and PD, was associated with erosion progression after 12 months. Calprotectin was associated with bone edema, in an exploratory analysis.

OP0348 Mass spectrometry imaging analysis of synovium differentiate patients with psoriatic and rheumatoid arthritis

Background Rheumatoid arthritis (RA) and Psoriatic arthritis (PsA) are systemic inflammatory diseases characterised by a chronic form of arthritis, often leading to irreversible joint damage. Both are highly heterogeneous and complex disorders, presenting major challenges in diagnosis and treatment. The signs and symptoms of RA and PsA are similar especially at the earlier phases of the disease, so it can be difficult to distinguish them on clinical grounds. Lipids and metabolites have been associated with pathological events in both diseases as contributors of the inflammation process. Accordingly, the local lipidome and metabolome from the inflamed tissue may be more reliable in predicting the disease status than the current diagnostic methods, since the synovium is one of the main target tissues of both pathologies. Objectives To identify lipid and metabolic profiles in the synovium using Mass Spectrometry Imaging (MSI) that would have the potential to distinguish between patients with RA and PsA. Methods Synovium biopsies from 25 patients with PsA, 21 with RA (16 seropositive and 5 seronegative) and 10 with IA (Indeterminate arthritis) were included. Tissue sections were deposited on conductive slides and coated with different matrices for lipid and metabolite extraction. MALDI images were acquired on a rapifleX MALDI Tissuetyper time-of-flight instrument. Multivariate data analysis was used to look for the lipids and metabolites with the highest differences among groups. Results MALDI-MSI revealed differential lipid and metabolic profiles among all compared groups. Discriminant analysis (DA) performed on lipid data acquired in positive ion mode displayed a good separation of patients with PsA and RA, especially seropositive RA (figure 1A). PsA showed higher lipid content, mainly phospholipids and sphingolipids, compared to seropositive RA (figure 1B and 1C). Some of them showed a specific localization within tissue. Experiments performed in negative ion mode showed that phosphatidylinositols and phosphatidic acids content varied among groups. Accordingly, DA allowed the separation of PsA from RA and IA patients, mainly from seronegative RA. PsA and RA groups were also distinguished based on synovium metabolic signatures. Sugars including N-acetylhexosamine 6-sulfate (m/z 282.0276), glucuronic acid 1-phosphate (m/z 273.0026) and N-acetylneuraminic acid (m/z 290.0876) displayed a stronger intensity in RA synovium when compared to PsA.Abstract OP0348 – Figure 1 A) Histogram distribution and B) Discriminant function 1 (DF1) loading plot. DF1 negative scores are specific to PsA synovial tissue and positive scores to seropositive RA. C) Spatial mapping positive-lipid ions in synovium sections. Scale bar shows normalised intensities. Conclusions For the first time, PsA and RA synovial membranes have been classified by MALDI-MSI. PsA synovium was characterised by a higher content of phospholipids compared to seronegative and seropositive RA. However, sugar metabolites displayed a stronger intensity in RA synovium when compared to PsA. Metabolic and lipid signatures here reported could support clinical decision-making in the diagnosis of RA and PsA. Disclosure of Interest None declared