P. Emery

NIHR Leeds Musculoskeletal Biomedical Research Unit

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Edward M Vital

Leeds Teaching Hospitals NHS Trust

Md Yuzaiful Md Yusof

NIHR Leeds Musculoskeletal Biomedical Research Unit

E. Hensor

NIHR Leeds Musculoskeletal Biomedical Research Unit

Philip G. Conaghan

University of Leeds

MH Buch

NIHR Manchester Biomedical Research Centre

Dennis McGonagle

University of Leeds

E. C. Hsia

University of Pennsylvania

Yasser M. El‐Sherbiny

Nottingham Trent University

T. Huizinga

Leiden University Medical Center

Andrew Gough

Medway NHS Foundation Trust

Cooperative Institutions

Leiden University

273

University of the Gambia

193

University of Leeds

169

NIHR Leeds Musculoskeletal Biomedical Research Unit

124

Center for Rheumatology

111

Imperial College Healthcare NHS Trust

109

Leeds Teaching Hospitals NHS Trust

102

University College London

101

University of Manchester

King's College London

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Liver disease in twins with Felty's syndrome.

Annals of the Rheumatic Diseases (1994)

Robert J. Moots Elwyn Elias S. Hubscher M Salmon P. Emery

In 1924 Felty reported the association of rheumatoid arthritis (RA), splenomegaly and neutropenia.'Other features including throm- bocytopenia, anaemia, generalised lympha- denopathy, skin ulcers and hyper pigmentation have been added and it has become generally accepted that Felty's syndrome (FS) is an uncommon but severe variant of RA, developing in approximately 1% of patients.2Affected patients tend to have a severe, de- structive arthritis despite little evidence of objective synovitis, and exhibit a higher frequency of extra-articular manifestations, including vasculitis.Although the aetiology of FS, in common with RA, is unknown, over 900/o of patients are HLA-DR4 positive, com- pared with 70% of patients with RA and only 30/o of controls, suggesting a genetic basis:3 indeed, a striking proportion are homozygous for the HLA-Dw4 allele.4In this article liver disease, one of the less well-known associations of FS, is discussed, and stresses the clinical features, investigations, aetiopathology, and management.

Felty's syndrome

10.1136/ard.53.3.202

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THE EFFICACY OF CERTOLIZUMAB PEGOL ADDED TO METHOTREXATE IS SUSTAINED OVER 2 YEARS IN THE TREATMENT OF RHEUMATOID ARTHRITIS

Lara D. Veeken (2010)

E. Keystone R. Fleischmann J S Smolen Vibeke Strand Robert Landewé

Certolizumab pegol

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Citations (1)

THU0101 Cardiovascular magnetic resonance imaging characterisation of cardiovascular abnormalities in individuals at risk of developing rheumatoid arthritis

Annals of the Rheumatic Diseases (2017)

G. Fent Laura Hunt KS Mankia Bara Erhayiem JR Foley

Background

Inflammation is the primary contributor to excess cardiovascular (CV) disease in rheumatoid arthritis (RA), with evidence of subclinical abnormalities observed even in treatment-naïve, early RA [1]. Preliminary reports suggest citrullinated proteins are present in atherosclerotic plaque [2]. It is unclear whether immunological changes of anti-citrullinated protein antibody (anti-CCP+) positive individuals "at risk" of developing RA are associated with CV abnormality.

Objectives

To perform a pilot study to explore whether subclinical CV abnormalities are present in anti-CCP+ individuals at risk of developing RA.

Methods

Sixteen consecutive patients with non specific MSK symptoms but no synovitis, detectable anti-CCP antibody and 30 age-matched healthy controls (HC) underwent a multi-parametric 3.0T (Philips Achieva) cardiovascular magnetic resonance (CMR) study. Neither group had any history of CV disease. At-risk individuals were categorised as low and high absolute risk for RA development (<50% and ≥50% respectively) according to a published risk model [3]. CMR post-processing was performed using CVI ⁴² (Circle Cardiovascular Imaging, Canada).

Results

HC and at risk individuals were well matched for baseline characteristics (table 1). Aortic strain values (distensibility, strain and stiffness index β) were lower, indicating increased aortic stiffness, in at-risk individuals than HC, numerically most pronounced those classified high risk (table 2). There were no differences in LV mass and function, late gadolinium enhancement, myocardial T1 (measure of myocardial composition) or LV S prime (longitudinal LV systolic function) (table 2).

Conclusions

Anti-CCP+ individuals with non-specific MSK symptoms (in particular, a high risk group), exhibit increased aortic stiffness. This suggests presence of CV abnormalities prior to development of RA and implies a role of autoantibody-mediated development of atherosclerosis. These findings warrant further investigation in larger scale studies.

References

Erhayiem B et al. Newly diagnosed, treatment-naive patients with rheumatoid arthritis have early abnormalities of vascular and myocardial function. J Cardiovasc Magn Reson 2015;17:P285. Sokolove J et al. Brief report: citrullination within the atherosclerotic plaque: a potential target for the anti-citrullinated protein antibody response in rheumatoid arthritis. Arthritis Rheum 2013;65:1719–24. Rakieh C et al. Predicting the development of clinical arthritis in anti-CCP positive individuals with non-specific musculoskeletal symptoms?: a prospective observational cohort study. Ann Rheum Dis 2015;74:1659–1656.

Disclosure of Interest

None declared

10.1136/annrheumdis-2017-eular.4969

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Antibodies to protein P in systemic lupus erythematosus.

Annals of the Rheumatic Diseases (1992)

Lee‐Suan Teh Alice Bedwell David Isenberg Caroline Gordon P. Emery

A synthetic peptide was used to develop an enzyme linked immunosorbent assay (ELISA) to detect antibodies to the ribosomal proteins P0, P1, and P2. Significantly increased levels of IgG antibodies to protein P were found in 16% (18/116) of patients with systemic lupus erythematosus but slightly increased levels were detected in 2% (2/98) of patients with rheumatoid arthritis and one normal control subject. No association was observed between the presence of IgG antibodies to protein P and either lupus psychosis or depression. Sequential studies in individual patients failed to show an association between antibody levels and the development of psychosis.

Blisibimod

10.1136/ard.51.4.489

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Citations (80)

Autologous stem cell transplantation in rheumatoid arthritis

John A. Snowden John J. Moore Passweg Paul Cannell Jacob M. van Laar

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The subgingival microbiomes in periodontitis and health of individuals with rheumatoid arthritis and at risk of developing rheumatoid arthritis

Journal of Oral Microbiology (2017)

Zijian Cheng Thuy Do Kulveer Mankia J.L. Meade Laura Hunt

ABSTRACTABSTRACTSerum anti-citrullinated protein antibodies (ACPAs), present in 70% of people with rheumatoid arthritis (RA), can be detected ≤10years before the onset of clinical disease. RA and periodontitis are epidemiologically associated and we have reported a high incidence of periodontitis in people who are ACPA+ and at risk of RA. Periodontal bacteria may contribute by multiple routes to the generation of RA-autoantibodies. This study aims to characterise the subgingival microbiomes from periodontitis and health in individuals with/without RA and at risk of RA.Forty-five ACPA+ no RA (RA-at-risk; RAR), 31 healthy controls (HC) and 30 ACPA+ RA patients (RA) underwent a periodontal examination. DNA from subgingival plaque from healthy and deep pocket sites were paired-end sequenced using the Illumina HiSeq3000 and data analysed using MG-RAST + DESeq.Metagenomes in RA samples had high proportions of Actinobacteria; RAR microbiomes contained higher proportions of Bacteroidetes than HC. The relative abundance of P. gingivalis was high in periodontitis and RAR; Aggregatibacter actinomycetemcomitans was detected with similar frequency in each group. Other bacteria implicated in periodontitis and/or autoantibody generation (Filifactor alocis, Prevotella spp, Leptotrichia spp.) were detected. Analyses are on-going to elucidate the diversity and functional potential of the subgingival microbiome associated with RA.

Aggregatibacter actinomycetemcomitans

Prevotella intermedia

10.1080/20002297.2017.1325216

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Citations (4)

AB0502 CELLULAR AND PROTEOMIC CHANGES FOLLOWING ADMINISTRATION OF PERESOLIMAB, IN A PHASE 2A TRIAL IN RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases (2024)

Robert J. Benschop Jay Tuttle P. Emery Christoph Preuß Montanea Daniels

10.1136/annrheumdis-2024-eular.626

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EARLY EFFECT OF SECUKINUMAB IN REDUCING SPINAL INFLAMMATION AS DETECTED BY MAGNETIC RESONANCE IMAGING IN PATIENTS WITH ANKYLOSING SPONDYLITIS

Lara D. Veeken (2012)

Jacob M. van Laar Xenofon Baraliakos Jürgen Braun Didier Laurent Dominique Baeten

Spondylitis

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FRI0468 High Prevalence of Us Determined Subclinical Synovitis in Early Psoriatic Arthritis Correlates Better with The SJC Rather than TJC: Results from The Leeds Sparro Cohort: Table 1.

Annals of the Rheumatic Diseases (2016)

Mira Merashli Laura Horton E. Hensor Gabriele De Marco Maria Antonietta D’Agostino

Background

Ultrasound (US) is known to be more sensitive than clinical examination in detecting synovitis in psoriatic arthritis (PsA). However, some studies found disparity between the US and clinical findings

Objectives

To assess the prevalence of synovial involvement in early PsA using clinical and sonographic assessments.

Methods

A total of 49 subjects with early PsA (CASPAR criteria) recruited in the Leeds Spondyloarthropathy Register for Research and Observation (SpARRO) study, a prospective longitudinal observational cohort, was assessed. The mean disease duration is 1.6 ±0.5 years; F:M ratio is 1.3; median SJC76 is 2 (1–2), median TJC78 is 6 (3–17); 90% of subjects had current skin psoriasis. Baseline US scan was performed on 1274 joints including bilateral wrists, MCP2–3, PIP2–3, elbows, knees, ankles & MTP 1–5. Grey Scale (GS) and Power Doppler (PD) were scored on a 0–3 semi-quantitative scale for each joint. Joints were considered clinically active if tender or swollen, and sonographically active if GS≥2 and/or PD≥1. We compared US active (yes/no) against tender (yes/no) and swollen (yes/no). The majority of the patients (88%) were DMARD naive

Results

US identified a higher proportion of subclinical synovitis among swollen rather than tender joints in subjects with early PsA. The agreement between clinical examination (tender & swollen) and US findings was high (73 & 87%) respectively. The most common sites for subclinical synovitis were MTP joints. In contrast, wrist tenderness and MTP2 swelling were the highest overestimated joints among the physical examination.

Conclusions

The prevalence of subclinical synovitis is high in early PsA. Joint swelling is more likely to correlate with PD or GS in PsA when compared to joint tenderness. As opposed to RA, where clinical tenderness correlates with subclinical synovitis, the tender joint count may not be a reliable clinical measure to assess synovitis in PsA. Possible reasons for the over-estimation of TJC in clinical examination may be the concomitant occurrence of fibromyalgia. Larger studies are needed to confirm our results.

Disclosure of Interest

None declared

Subclinical infection

Concomitant

10.1136/annrheumdis-2016-eular.4630

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FRI0390 European multicentre study validates elf test as biomarker of fibrosis in systemic sclerosis

Annals of the Rheumatic Diseases (2017)

Giuseppina Abignano Jelena Blagojević L-A Bissell RB Dumitru Sookhoe Eng

Background

The Enhanced Liver Fibrosis (ELF) test is a serum test including the serum concentrations of amino-terminal pro-peptide of procollagen type III (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and hyaluronic acid (HA). A recent single centre study showed that ELF score and its components are markers of overall fibrosis in systemic sclerosis (SSc) mainly reflecting skin and lung involvement (1).

Objectives

To determine the value of ELF score and its single analytes in an independent multicentre cohort of SSc patients.

Methods

254 SSc patients from 6 European Rheumatology Centres were included in this study. Clinical data were collected at time of sampling. Serum samples were collected and stored according to EUSTAR biobanking recommendations (2). Sera were analysed employing a high-throughput in vitro diagnostic (Siemens Alpha-Centaur). Statistical analysis was performed with SPSS software V.24.

Results

The 254 SSc patients had a mean age 55.8±13.8 years, and included 209 females and 80 patients with diffuse cutaneous SSc (dcSSc). ELF score was overall higher in males than in females (p=0.0236) as well as in dcSSc compared to limited cutaneous SSc patients (p=0.0015). ELF score and the single markers significantly correlated with the degree of skin involvement (mRSS) and inversely correlated with FVC%, TLC% and DLCO%. Concordantly all markers significantly correlated with skin and lung severity as assessed by the Medsger9s scale (Table 1). TIMP-1 and PIIINP levels were higher in patients with lung fibrosis assessed by chest HRCT scan (p=0.0126 and p=0.0308 respectively). Significant correlation (p<0.0001) was found between ELF score, TIMP-1, PIIINP, HA and total disease severity and activity. Multivariate analysis indicated that age (p<0.0001), mRSS (p<0.0001) and DLCO% (p=0.005) were independently associated with ELF score.

Conclusions

The value of ELF score as independent marker of skin and lung involvement is confirmed in a second independent multicentre cohort of SSc patients. A longitudinal study paired with analysis of large cohort of healthy controls is currently on going to identify a SSc specific test with the highest predictive value for skin and lung progression independently of age and gender.

References

Abignano G et al. Ann Rheum Dis. 2014. Beyer C et al. Ann Rheum Dis. 2011.

Disclosure of Interest

None declared

DLCO

10.1136/annrheumdis-2017-eular.3236

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