OBJECTIVES Predicting response to anti-tumour necrosis factor alpha (anti-TNFα) drugs at baseline remains an elusive goal in rheumatoid arthritis (RA) management. The purpose of this study was to determine if baseline genetic variants of PTPRC, AFF3, myD228, CHUK, MTHFR1, MTHFR2, CD226 and a number of KIR and HLA alleles could predict response to anti-TNF-α in rheumatoid arthritis patients. METHODS Peripheral blood samples were collected from 238 RA patients treated with anti-TNFα drugs. Genotyping was performed using biochip array technology by Randox Laboratories Ltd. and sequence specific polymerase chain reaction. Linear regression analysis was performed to investigate the role of these genotypes in predicting response to treatment, as defined by European League Against Rheumatism (EULAR) response classification and absolute change in disease activity score (DAS28). RESULTS Of 238 RA patients analysed, 50.4% received adalimumab, 29.7% received etanercept, 14.8% received infliximab, 3.4% certoluzimab and 1.7% golimumab. The MTHFR1 variant rs1801133 was significantly associated with the EULAR response, p=0.044. Patients with the HLA-DRB1*0404 allele displayed a significantly larger reduction in DAS28 compared to non-carriers (mean -2.22, -1.67 respectively, p=0.033). CD226 rs763361 was the only SNP variant significantly associated with ΔDAS28 (p=0.029). CONCLUSIONS This study has investigated individual allele associations with reductions in DAS28 across a range of anti-TNFα treatments. A combined predictive model indicates that patients with the HLA-DRB1*0404 allele and without the CD226 rs763361 polymorphism exhibit the largest reduction in DAS28 after anti-TNF-α treatment.

Abstract Background Rheumatoid arthritis (RA) is an autoimmune condition characterised by inflamed joints. Disease-modifying anti-rheumatic drugs (DMARD) are ineffective in 30–40% of patients. CD169 (Siglec-1) is expressed by monocytes and correlates with disease activity in RA. It drives pro-inflammatory processes including the suppression of Tregs through its cognate ligand, CD169L. This study aims to define the relationship between CD169, CD169L and disease activity, as a potential early biomarker of treatment response. Methods Peripheral blood mononuclear cells were isolated from healthy controls and RA patients who failed DMARD treatment. FACS was used to: (i) immunophenotype CD169+ monocytes and CD169L+ Tregs, and (ii) assess levels of FoxP3 within Tregs. Results RA patients had a significantly higher percentage of CD169+ monocytes (28.47 ± 7.17, (mean ± SEM), n=19) compared to healthy controls (8.03 ± 1.48, n=19, p=<0.01). A negative correlation was also observed between the percentage of CD169+ monocytes and CD169L+ Tregs in RA patients (r=−0.72, n=19, p=<0.01). Furthermore, the ratio of CD169:CD169L percentages has a positive association with DAS28-ESR (r=0.77, n=9, p=0.02). FoxP3 is expressed at lower levels in RA patients (24.14 ± 1.87, n=25) compared with healthy controls (46.65 ± 6.16, n=13, p=<0.01). Conclusion These results provide preliminary evidence of a relationship between CD169 and CD169L, and further define how their balance is associated with disease activity. Low levels of FoxP3 in RA patients indicates reduced Treg activation, which may cause increased disease activity. We postulate that this balance of cells is key in the immune response and could be used as a surrogate measure of disease activity.

OBJECTIVES:To conduct a training course in musculoskeletal ultrasound (MSUS) for rheumatologists in Northern Ireland with the aim of equipping the participants with a basic knowledge of the theoretical and practical aspects of MSUS as they are applied to rheumatology.METHODS:Between September 2007 and June 2008, 10 rheumatologists attended a course in basic MSUS that was delivered by 7 rheumatologists with experience in MSUS. The course consisted of five separate modules that included tutorials on MSUS, self-directed learning of scanning techniques and personal mentoring. Progress was monitored throughout the course by the use of personal logbooks. Competency was formally assessed using the Royal College of Physicians' Direct Operational Procedural Skills (DOPS) assessment and an exit examination.RESULTS:Five trainees completed the entire course and passed both the practical and written elements of the exit examination. All were deemed to have attained a basic level of competency in MSUS. The main obstacle to completion of the course was a lack of scanning practice and an inability to complete the required number of scans and DOPS assessments. Participants were more likely to fulfil the requirements of the course if they were employed full time in the regional rheumatology unit where the course was based. All participants reported high levels of confidence in their basic scanning skills at the conclusion of the course. They also felt that the training enhanced their clinical examination skills and their understanding of musculoskeletal anatomy.CONCLUSIONS:A basic MSUS training course can be successfully delivered using a modular design that takes account of the trainee's level of experience and their work schedule. Important elements of such a course should include personal mentoring and the recording of scanning activity using a logbook. Periodic assessment of the trainee's performance is a useful means to motivate learning. Basic training in MSUS should become an accepted part of the routine training of rheumatologists in the UK.

The frequency of inhibiting and activating killer cell immunoglobulin-like receptors was similar in 331 patients with rheumatoid arthritis and in 354 controls. Patients and controls came from a relatively homogeneous Caucasian population from Northern Ireland, thus limiting population stratification. Furthermore, no differences were found when the patients were sub-divided according to gender or shared epitope and when the presence of the human leucocyte antigen ligand was taken into account.

proportion of patients with end-stage kidney disease [10]. The associated cardiovascular comorbidities of such patients make the significance of this finding unknown but an association with underlying inflammatory disease cannot be excluded. In summary, while markers of atherosclerosis are well recognized in systemic vasculitis and autoimmune disease, we report the first case series of myocardial fibrosis using CMR in these conditions. This raises the possibility that immune mediated damage as well as atherosclerotic disease may contribute to myocardial injury in these patients.

OBJECTIVETo replicate, in a Northern Irish population, the previously reported association between a locus on chromosome 6 and hip osteoarthritis (OA).METHODSPatients with hip OA were identified from a registry of patients who had undergone total hip replacement surgery over an 8-year period at a single large orthopedic unit in Northern Ireland. Patients identified as index cases were contacted by mail and asked to reply only if another family member also had undergone total hip replacement surgery. Using this approach, we identified 288 sibling pairs concordant for primary hip OA. DNA was extracted from peripheral blood, and microsatellite markers were amplified by polymerase chain reaction and subsequently genotyped.RESULTSNo evidence of linkage to this region was demonstrated by either 2-point analysis or multipoint analysis of 17 microsatellites.CONCLUSIONThe reported association between a locus on chromosome 6 and hip OA could not be confirmed in this population. Different methods of ascertainment and phenotyping of OA may contribute to the current inability to replicate genetic associations for hip OA.

allopurinol, suppressed both plasma and articular XOR activity at <0.3% of normal levels. However, XOR inactivation was associated with greater in- crease of knee swelling at 24 and 48 hrs post i.a. mBSA, compared with controls (mean increase ± SEM of knee diameter from baseline of 3.3±0.5, 2.0±0.3 and 1.9±0.2 mm in the TG, SG and AG groups (n=14 each group), respectively;p<0.05, TG vs. SG (ANOVA, Dunnett's post-test). Mean ra- tio of articular nitrotyrosine-tyrosine (±SEM) was increased in the XOR- inactivated group, compared with controls: 12.3±0.7, 9.6±0.8 and 10.4±0.5 pg/µg in the TG, SG and AG groups, respectively; p<0.05, TG vs. SG. No erosive joint damage was observed. Conclusions: XOR inactivation was associated with increased joint swelling and articular tyrosine nitration in acute AIA. This may suggest a novel, pro- tective role for XOR in inflammatory arthritis. Background: The relationship of rheumatoid arthritis (RA) with the "shared epitope" is well recognised. The "shared epitope" is located on the short arm of chromosome 6 and encodes for a sequence of amino acids that lie in close proximity to T cell receptor. It is thought to modify an individual's immune response. In Caucasian populations DR4 and DR1 are the most commonly expressed alleles. Its presence is associated with a more aggressive disease process and a worse prognosis. The aim of this study was to determine if the expression of this genotype influences the pathological changes that occur within the synovium in early RA. Methods: Thirteen patients with early RA were genotyped from a periph- eral blood sample for the "shared epitope" using an automated polymerase chain reaction technique. A synovial tissue sample was obtained using a blind needle technique prior to commencement on treatment. Up to three biopsies were analysed from each patient. This tissue was stained using an immunohistochemical technique for T cells (CD3), T helper cells (CD4), cytotoxic T cells (CD8), B cells (CD20), blood vessels (Factor VIII) and macrophages (CD68). Each marker was quantified using a manual counting technique to give an average percentage positive cell count for each biopsy. The CD68 marker was analysed by determining the percentage area of posi- tivity per biopsy. Statistical comparisons between groups of "shared epitope" positive and negative were made using the student's independent sample t test. Results: Six patients were shared epitope positive- 2 for 0101, 3 for 0401 and 1 compund hetereozygote, 0101 0401. CD3, CD4 and CD8 postive cells were present in significantly higher numbers in patients that were " shared epitope" positive (p=0.000, p=0.000 and p=0.004 respectively). There was no difference in blood vessel or macrophage counts between the two groups. Conclusions: The "shared epitope" genotype is associated with the level of inflammatory infiltrate within the synovium in early RA. Patients carrying the "shared epitope" have a higher T cell, T helper and cytotoxic T cell in- filtrate. These T cells are thought to play an important role in the initiation and perpetuation of the inflammatory process in early RA. This is a poten- tial explanation of the erosive joint disease process often seen in patients carrying these alleles. There did not appear to be a relationship with other inflammatory changes within the synovium which may imply that the effect of the "shared epitope" is limited to T cells. These findings however would need to be verified on a larger patient cohort.