Karim Raza

University of Birmingham, Birmingham, England, United Kingdom

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Publications (108)540.44 Total impact

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    ABSTRACT: To examine the diagnostic outcomes associated with clinical ankle synovitis in an early inflammatory arthritis cohort.
    Clinical and experimental rheumatology 07/2014; · 2.66 Impact Factor
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    ABSTRACT: Background Early treatment for rheumatoid arthritis (RA) is vital. However, people often delay in seeking help at symptom onset. An assessment of the reasons behind patient delay is necessary to develop interventions to promote rapid consultation.Objective Using a mixed methods design, we aimed to develop and test a questionnaire to assess the barriers to help seeking at RA onset.DesignQuestionnaire items were extracted from previous qualitative studies. Fifteen people with a lived experience of arthritis participated in focus groups to enhance the questionnaire's face validity. The questionnaire was also reviewed by groups of multidisciplinary health-care professionals. A test–retest survey of 41 patients with newly presenting RA or unclassified arthritis assessed the questionnaire items' intraclass correlations.ResultsDuring focus groups, participants rephrased questions, added questions and deleted items not relevant to the questionnaire's aims. Participants organized items into themes: early symptom experience, initial reactions to symptoms, self-management behaviours, causal beliefs, involvement of significant others, pre-diagnosis knowledge about RA, direct barriers to seeking help and relationship with GP. The test–retest survey identified seven items (out of 79) with low intraclass correlations which were removed from the final questionnaire.Conclusion The involvement of people with a lived experience of arthritis and multidisciplinary health-care professionals in the preliminary validation of the DELAY (delays in evaluating arthritis early) questionnaire has enriched its development. Preliminary assessment established its reliability. The DELAY questionnaire provides a tool for researchers to evaluate individual, cultural and health service barriers to help-seeking behaviour at RA onset.
    Health expectations: an international journal of public participation in health care and health policy 06/2014; · 1.80 Impact Factor
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    ABSTRACT: Objective. The aim of this study was to explore symptoms and symptom development during the earliest phases of RA in patients with seropositive arthralgia and patients newly diagnosed with RA.Methods. Interviews were conducted with 15 seropositive patients (anti-CCP positive, and often with arthralgia) and 11 newly presenting RA patients [classified according to the 2010 ACR/European League Against Rheumatism (EULAR) criteria]. Feedback procedures shared the experiences of seropositive arthralgia patients with early RA patients and vice versa. Data were analysed using thematic analysis.Results. Symptoms common to both groups included joint pain, psychological distress, muscle cramps, abnormal skin sensations, stiffness, loss of motor control, weakness, fatigue and sleeping difficulties. Also, patterns of symptom evolution and the order of symptom development were described. Seropositive arthralgia patients described pain as annoying, while RA patients described how the severity of pain intensified before diagnosis, to the point where symptoms were psychologically distressing. Patients with seropositive arthralgia described reddening of the skin and burning sensations that they felt were indicative of the onset of swelling. Intense pain appeared to precede the onset of swelling for those with RA, which was often palindromic and travelled between joints until it later became persistent.Conclusion. This study highlights the breadth of symptoms that constitute the earliest phases of RA. Further research is needed to develop measures of symptom patterns and clusters to allow the predictive utility of symptoms to be assessed and to allow the integration of aspects of the patient's history into evidence-based investigative and management algorithms for use in primary and secondary care.
    Rheumatology (Oxford, England) 04/2014; · 4.24 Impact Factor
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    ABSTRACT: Variation in endogenous glucocorticoid (GC) activity during inflammation has been linked to susceptibility to developing rheumatoid arthritis (RA). In RA patients, inflamed synovial tissue can generate active GCs through the expression of the 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1), which converts cortisone to cortisol. We examined whether the total body activity of 11β-HSD1 or its expression within synovium was associated with the risk of developing RA in patients with newly presenting joint inflammation. Blood and urine were collected from 42 patients with inflammatory arthritis and a clinical symptom duration of less than 12 weeks; of these 17 developed RA and 25 resolved spontaneously. Total body 11β-HSD1 activity was determined by urinary gas chromatography/mass spectrometry and calculated as the tetrahydrocortisol + allotetrahydrocortisol/tetrahydrocortisone ((THF + alloTHF)/THE) ratio and the cortols/cortolones ratio. Urinary 11β-HSD2 activity was measured as the urinary free cortisol/ urinary free cortisone (UFF/UFE) ratio. Synovial tissue expression of 11β-HSD1 and 11β-HSD2 was assessed by qPCR. Inflammatory disease activity was assessed by ESR, CRP and DAS28. Total body 11β-HSD1 activity was significantly lower in patients with arthritis that subsequently resolved compared with patients whose arthritis developed into RA (RA 1.34 ± 0.013, Resolving arthritis, 0.96 ± 0.07, P = 0.012). Similar changes were seen in the cortols/cortolones ratio (RA 0.64 ± 0.05, Resolving arthritis, 0.43 ± 0.03, P = 0.0002). There was no significant difference in renal 11β-HSD2 activity between patients with resolving disease and those that developed RA. Despite the difference in total body 11β-HSD1 activity there was no significant difference between groups in synovial tissue 11β-HSD1 expression. There was no difference in ESR or DAS28 between patients with resolving arthritis or RA although the former had a significantly lower level of CRP (RA, 49 ± 16.7 mg/dL, Resolving arthritis 19 ± 5.7 mg/dL, P = 0.018). All values are represented as mean ± SEM. These studies demonstrate that a high total body 11β-HSD1 activity during early arthritis is associated with a reduced probability of resolution. The excess 11β-HSD1 may have an articular and/or extra-articular origin. This work raises the possibility that targeting 11β-HSD1 activity in early arthritis could impact on the development of RA.
    Annals of the rheumatic diseases 03/2014; 73 Suppl 1:A12-3. · 8.11 Impact Factor
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    ABSTRACT: Fibroblasts actively regulate the recruitment of leukocytes by endothelial cells (EC), acting in a pro- or anti-inflammatory manner depending on their site of origin. The phenotype of the fibroblast may be a critical determinant of whether leukocyte recruitment, and therefore inflammation, resolves or persists. Here we examined how synovial fibroblasts from different stages of arthritis influenced the recruitment of peripheral blood lymphocytes (PBL) and their onward migration. Fibroblasts were isolated from patients with resolving or persistent arthritis. Rheumatoid arthritis (RA) cohorts were categorised based on the stage of disease at the time of sample collection: very early (≤ 12wk duration); newly presented established (>12 wk duration) or long established undergoing replacement surgery. Endothelial-fibroblast co-cultures were formed on either side of porous filters, and PBL adhesion was assessed using phase-contrast microscopy. Rheumatoid fibroblasts increased PBL recruitment in a disease duration-dependent manner (early RA <newly established <established, replacement). However, similar levels of binding were observed when fibroblasts from resolving or early RA tissue were incorporated. These data indicate that early RA and established, replacement fibroblasts have distinct phenotypes, where fibroblast in early RA have yet to acquire the ability to stimulate recruitment. When exogenous cytokines were added, co-cultures incorporating fibroblasts from resolving tissues suppressed PBL recruitment in an IL-6 and TGF-b dependent manner. Interestingly this immunosuppressive effect was lost in early RA, indicating that these fibroblasts lose their immunosuppressive phenotype early in disease development. Moreover, the mode of action of IL-6 and TGFb are hijacked in early RA, such that they no long suppress recruitment supporting aberrant lymphocyte infiltration. Fibroblasts from acutely resolving and early persistent arthritis are distinct. The latter lose immunosuppressive capability and acquire modifications towards a pro-inflammatory phenotype early in the disease process, even before clinical criteria are fulfilled. They may thus induce recruitment or inappropriately support cytokine-driven recruitment, leading to an accumulation of PBL in the rheumatoid joint.
    Annals of the rheumatic diseases 03/2014; 73 Suppl 1:A19. · 8.11 Impact Factor
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    ABSTRACT: Within the context of a comprehensive study of the pathology of the early stages of rheumatoid arthritis (RA) we compared cytokine mRNA expression in the synovium of patients with early inflammatory arthritis who later progressed to rheumatoid arthritis with that of patients with a resolving disease course. Interestingly, we found a trend towards higher expression of platelet related chemokines CXCL4 and CXCL7 mRNA in early RA synovium. We therefore investigated CXCL4 and CXCL7 expression at the protein level and its co-localisation with platelets, macrophages and blood vessels. Synovial tissue biopsies were obtained from treatment naïve patients presenting with at least one clinically swollen joint within the first 12 weeks of symptom onset. Patients who went on to develop RA (according to the 1987 ACR criteria) at an 18 month follow-up (n = 8), as well as patients whose arthritis spontaneously resolved (n = 9) were included. In addition, biopsies collected from longer duration (> 12 weeks) treatment naïve RA patients (n = 10) and patients with mechanical symptoms undergoing knee arthroscopy without obvious signs of inflammation were included as controls (n = 7). Synovial tissue sections were stained with antibodies specific to CXCL4 or CXCL7, CD41, CD68 and vWF using immunofluorescence and staining was quantified using Zeiss imaging software. Specificity of CXCL7 staining was confirmed by blocking with recombinant cytokine. We observed a statistically significant increase of CXCL4 and CXCL7 protein expression in patients with early RA when compared to early resolvers (CXCL4 p = 0.036, CXCL7 p = 0.011). This increase reflected a transient stage of early disease, as in treatment-naïve patients with more than 12 weeks disease duration the expression level of these chemokines was found at levels comparable to non-inflamed synovium. Both CXCL4 and CXCL7 co-localised with blood vessels, platelets and CD68(+) macrophages within the synovial tissue. However, only staining found outside blood vessels, which co-localised largely with CD68 as a marker for macrophages, differed between synovium from patients with resolving, early and established arthritis (CXCL4 p = 0.063, CXCL7 p = 0.028). We have identified two chemokines, CXCL4 and CXCL7, that are expressed at higher levels on macrophages during a transient phase in early RA. Future work will investigate whether these chemokines play a role in disease progression and/or may be used as biomarkers for prediction of disease outcome.
    Annals of the rheumatic diseases 03/2014; 73 Suppl 1:A28-9. · 8.11 Impact Factor
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    ABSTRACT: The importance of B cells in the pathogenesis of rheumatoid arthritis (RA) is highlighted by the clinical effectiveness of rituximab. Potential mechanisms for B cells in driving disease processes include autoantibody production, antigen presentation and cytokine secretion. Our recent findings suggest a pro-inflammatory and destructive role for B cells via production of RANKL, TNF-α and IL-6. A memory B cell subset in tonsils which expresses Fc receptor-like 4 (FcRL4) has previously been found to produce RANKL. We sought to determine whether the RANKL-expressing B cells present in the RA synovium belong to this subset. Methods: Synovial fluid and peripheral blood cells from RA patients were analysed for B cell differentiation markers by flow cytometry. Synovial tissue samples from RA patients were assessed using immunofluorescence and immunohistochemistry. FcRL4 mRNA expression was determined in synovial samples from RA patients and uninflamed control subjects by real-time PCR. FcRL4+ and FcRL4- CD19(+) B cells were sorted from synovial fluid using a MoFlo cell sorter. mRNA expression of 48 cytokines was determined using Taqman microfluidic cards. FcRL4 expressing B cells were detected in the synovial fluid (median 14% of B cells) at a significantly higher frequency compared to peripheral blood (median 0.04%; p = 0.004). RANKL was significantly enriched in the FcRL4+ B cell population compared to the FcRL4- population. FcRL4+ B cells were predominantly switched memory B cells, expressing significantly higher levels of CD80, CD86, CD95, CD20 and CD11c than FcRL4- cells. Sorted FcRL4+ B cells expressed significantly higher mRNA levels of RANKL and TNF-α than FcRL4- B cells. FcRL4+ B cells expressing RANKL were present in synovial tissue, and were distributed under the synovial lining layer and in perivascular cuffs. FcRL4 mRNA was detected in synovium from RA patients but not uninflamed controls, and FcRL4 expression in RA synovium correlated positively with the degree of leukocyte infiltration. We have identified a novel pro-inflammatory subset of B cells in the RA synovium which expresses RANKL and TNF-α and shows considerable expression of co-stimulatory molecules indicating a potential pathogenic role in RA. As these cells express high levels of CD20 it is conceivable that their removal contributes to the anti-inflammatory clinical effect of rituximab.
    Annals of the rheumatic diseases 03/2014; 73 Suppl 1:A22-3. · 8.11 Impact Factor
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    ABSTRACT: Endogenous glucocorticoids are implicated in the development and resolution of inflammation. Until recently it was thought that these glucocorticoids arose primarily from the adrenal gland. However, it is now known that several cell types can generate active glucocorticoids within their cytoplasm through expression of the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme. In a more limited range of cell types, glucocorticoids can be inactivated by the related 11β-HSD2 enzyme. Both enzymes are regulated by inflammation in various settings. In rheumatoid arthritis, 11β-HSD activity is present in the inflamed synovium and appears to influence articular and extraarticular disease processes. The generation of active glucocorticoids in the synovium is strongly linked to the level of inflammation. This local production of glucocorticoids is likely to have paracrine consequences and could underpin inflammation-associated bone loss. The role of 11β-HSD enzymes in the severity and persistence of inflammatory arthritis in a clinical setting is currently being explored.
    Annals of the New York Academy of Sciences 03/2014; · 4.38 Impact Factor
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    ABSTRACT: Abstract Objective. To explore general practitioners' (GPs') perspectives on public health campaigns to encourage people with the early symptoms of rheumatoid arthritis (RA) to seek medical help rapidly. Design. Nineteen GPs participated in four semi-structured focus groups. Focus groups were audio-recorded, transcribed verbatim, and analysed using thematic analysis. Results. GPs recognised the need for the early treatment of RA and identified that facilitating appropriate access to care was important. However, not all held the view that a delay in help seeking was a clinically significant issue. Furthermore, many were concerned that the early symptoms of RA were often non-specific, and that current knowledge about the nature of symptoms at disease onset was inadequate to inform the content of a help-seeking campaign. They argued that a campaign might not be able to specifically target those who need to present urgently. Poorly designed campaigns were suggested to have a negative impact on GPs' workloads, and would "clog up" the referral pathway for genuine cases of RA. Conclusions. GPs were supportive of strategies to improve access to Rheumatological care and increase public awareness of RA symptoms. However, they have identified important issues that need to be considered in developing a public health campaign that forms part of an overall strategy to reduce time to treatment for patients with new onset RA. This study highlights the value of gaining GPs' perspectives before launching health promotion campaigns.
    Scandinavian journal of primary health care 03/2014; 32(1):37-43. · 2.21 Impact Factor
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    ABSTRACT: The success of B cell targeting therapies has highlighted the importance of B cells in rheumatoid arthritis pathogenesis. We have previously shown that B cells in the RA synovium are capable of producing pro-inflammatory and bone-destructive cytokines including RANKL. Here we sought to characterise the nature and functional relevance of the RANKL-producing B cell subset in the RA synovium. Synovial fluid and peripheral blood B cells from patients with RA were analysed by flow cytometry for markers of B cell differentiation and activation and for chemokine receptors. FcRL4(+) and FcRL4(-) B cells sorted from synovial fluid were analysed for cytokine expression using Taqman low-density arrays. Synovial tissue biopsies obtained from patients with RA were analysed by immunofluorescence for CD20, RANKL and FcRL4. FCRL4 mRNA expression was determined in synovial tissue of RA patients and non-inflammatory control subjects by real-time PCR. RANKL-producing B cells in RA synovial tissue and fluid were identified as belonging to a distinct subset of B cells defined by expression of the transmembrane protein FcRL4. FcRL4+ B cells express a distinct combination of cytokines and surface proteins indicating a function distinct from that of FcRL4- B cells. Notably, FcRL4+ B cells expressed high levels of TNF-α and RANKL mRNA. We have identified a novel pro-inflammatory B cell population in the RA synovium which is defined by expression of FcRL4 and responsible for RANKL production. This B cell population expresses high levels of CD20, and its removal by rituximab may contribute to the anti-inflammatory effect of this drug.
    Annals of the rheumatic diseases 01/2014; · 8.11 Impact Factor
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    ABSTRACT: To determine the relationship between inflammation and glucocorticoid metabolism in vivo, in a clinical study of patients with inflammatory arthritis treated with anti-TNFα therapy. Urine samples were collected from patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) as part of a multicentre study assessing responses to infliximab and etanercept. Systemic measures of glucocorticoid metabolism were assessed by gas chromatography/mass spectrometry at weeks 0 (baseline), 4 and 12 after anti-TNFα therapy. Clinical data including DAS28 and C-reactive protein were also collected. Systemic measures of 11β-HSD1 activity in patients with inflammatory arthritis decreased significantly following anti-TNFα therapy in patients with RA and PsA. Additionally, the activity of the glucocorticoid inactivating enzyme 5α-reductase appeared to increase significantly. This study demonstrates, for the first time, that the increased 11β-HSD1 activity seen in patients with inflammatory arthritis is mediated through TNFα. Furthermore, the changes in related glucocorticoid metabolising enzymes suggest that there is a coordinated change in glucocorticoid metabolism which promotes higher tissue glucocorticoid levels.
    Annals of the rheumatic diseases 01/2014; · 8.11 Impact Factor
  • Karim Raza, Danielle M. Gerlag
    Rheumatic Disease Clinics of North America 01/2014; · 2.10 Impact Factor
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    ABSTRACT: Understanding the features and patterns of symptoms that characterise the earliest stages of rheumatoid arthritis (RA) is of considerable importance if patients are to be identified and started on treatment early. However, little is known about the characteristics of symptoms at the onset of a disease that eventually progresses to RA. A systematic review of qualitative peer-reviewed publications was conducted to identify the earliest symptoms associated with the onset of RA. 1736 abstracts were searched to identify relevant publications. Twenty-six publications were identified, assessed for quality and subjected to analysis informed by thematic and grounded theory frameworks. Several interacting themes describing the early symptoms of RA were identified including swelling, pain and tenderness, stiffness, fatigue and weakness and the emotional impact of symptoms. For each symptom, different and evolving intensities were described, in some cases patterns of symptoms onset and symptom complexes at the onset of RA were highlighted. Importantly, this review has highlighted major deficiencies in the literature. None of the studies reviewed originally aimed to explore symptoms at RA onset (often discussions about symptom onset were secondary to the study's primary aim). Also, many of the articles identified sampled people diagnosed with RA many years previously, making their recollection of symptom at onset less reliable. In order for clinicians to fully understand the earliest phases of disease the nature of symptoms at onset needs to be understood. The current work represents a useful starting point but this area needs further qualitative investigation. This should be followed by quantitative explorations of symptom clusters and their associated features. © 2013 American College of Rheumatology.
    Arthritis Care and Research 08/2013; 65(12):1916–1926. · 3.73 Impact Factor
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    ABSTRACT: Identification of parameters for early diagnosis and treatment response would be beneficial for patients with early rheumatoid arthritis (ERA) to prevent ongoing joint damage. miRNAs have features of potential biomarkers, and an altered expression of miRNAs was shown in established rheumatoid arthritis (RA). To analyse RA associated miRNAs in the sera of patients with ERA to find markers of early disease, clinical activity or predictors of disease outcome. Total RNA was isolated from whole sera in ERA patients (prior to and after 3 and 12 months of therapy with disease modifying antirheumatic drugs), in patients with established RA and in healthy controls (HC) using phenol-chloroform extraction. Expression of miR-146a, miR-155, miR-223, miR-16, miR-203, miR-132 and miR-124a was analysed by TaqMan Real Time PCR. From all analysed miRNAs, levels of miR-146a, miR-155 and miR-16 were decreased in the sera of ERA patients in comparison with established RA. A change in circulating miR-16 in the first 3 months of therapy was associated with a decrease in DAS28 in long term follow-up in ERA (p=0.002). Levels of circulating miR-223 in treatment naïve ERA correlated with C reactive protein (p=0.008), DAS28 (p=0.031) and change in DAS28 after 3 months (p=0.003) and 12 months (p=0.011) of follow-up. However, neither miR-16 nor miR-223 could distinguish ERA from HC. Differential expression of circulating miR-146a, miR-155 and miR-16 in the sera of ERA patients may characterise an early stage of the disease. We suggest miR-223 as a marker of disease activity and miR-16 and miR-223 as possible predictors for disease outcome in ERA.
    Annals of the rheumatic diseases 07/2013; · 8.11 Impact Factor
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    ABSTRACT: Eligibility for anti-tumour necrosis factor (TNF) therapy in most European countries is restricted to severe, active rheumatoid arthritis (RA). The DAS28 score is a marker of disease severity and incorporates one of two inflammatory markers, erythrocyte sedimentation rate (ESR) or C-reactive protein. We aimed to determine the relation between genetic variants known to affect ESR and levels of ESR in patients with active RA. DNA samples were genotyped for four single-nucleotide polymorphisms (SNPs) rs7527798 (CR1L), rs6691117 (CR1), rs10903129 (TMEM57) and rs1043879 (C1orf63). The association between SNPs and baseline ESR, baseline DAS28-ESR, and change in DAS28-ESR was evaluated. Baseline ESR was significantly associated with CR1 rs6691117 genotype (P=0.01). No correlation was identified between baseline DAS28-ESR or change in DAS28-ESR. In conclusion, genetic variation in the gene encoding CR1 may alter ESR levels but not DAS28-ESR, indicating no adjustment for CR1 genotype is required in the assessment of patients with severe active RA.The Pharmacogenomics Journal advance online publication, 16 July 2013; doi:10.1038/tpj.2013.26.
    The Pharmacogenomics Journal 07/2013; · 5.13 Impact Factor
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    ABSTRACT: Objectives: Genome-wide association studies have facilitated the identification of over 30 susceptibility loci for rheumatoid arthritis (RA). However, evidence for a number of potential susceptibility genes have not so far reached genome-wide significance in studies of Caucasian RA. Methods: A cohort of 4286 RA patients from across Europe and 5642 population matched controls were genotyped for 25 SNPs, then combined in a meta-analysis with previously published data. Results: Significant evidence of association was detected for nine SNPs within the European samples. When meta-analysed with previously published data, 21 SNPs were associated with RA susceptibility. Although SNPs in the PTPN2 gene were previously reported to be associated with RA in both Japanese and European populations, we show genome-wide evidence for a different SNP within this gene associated with RA susceptibility in an independent European population (rs7234029, P = 4.4610 29). Conclusions: This study provides further genome-wide evidence for the association of the PTPN2 locus (encoding the T cell protein tyrosine phosphastase) with Caucasian RA susceptibility. This finding adds to the growing evidence for PTPN2 being a pan-autoimmune susceptibility gene. Copyright: ß 2013 Cobb et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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    ABSTRACT: Objectives: Inflammatory arthritis is associated with systemic manifestations including alterations in metabolism. We have used NMR spectroscopy-based metabolomics to assess metabolite fingerprints in serum from patients with established rheumatoid arthritis (RA) and early arthritis. Methods: Serum samples were collected from newly presenting, disease-modifying drug naive patients with established RA, matched healthy controls, and two groups of patients with synovitis of ≤3 months' duration whose outcomes were determined at clinical follow-up. Serum metabolic profiles were assessed using 1D (1) H-NMR spectroscopy. Discriminating metabolites were identified, and the relationships between metabolic profiles and clinical variables including outcomes were examined. Results: The serum metabolite fingerprint in established RA was clearly distinct from that of healthy controls. In early arthritis, we were able to stratify the patients according to the level of current inflammation, with CRP correlating with metabolic differences in two separate groups (p<0.001). Lactate and lipids were important discriminators of inflammatory burden in both early arthritis patient groups. The sensitivities and specificities of models to predict the development of either RA or persistent arthritis in patients with early arthritis were low. Conclusions: The metabolomic fingerprint reflects inflammatory disease activity in patients with synovitis, demonstrating that underlying inflammatory processes drive significant changes in metabolism that can be measured in the peripheral blood. The identification of metabolic alterations may provide insights into disease mechanisms operating in patients with inflammatory arthritis. © 2013 American College of Rheumatology.
    Arthritis & Rheumatology 06/2013; · 7.48 Impact Factor
  • Karim Raza, Christopher D Buckley
    Current Opinion in Pharmacology 04/2013; · 5.44 Impact Factor
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    ABSTRACT: Objective. Early recognition and treatment of RA is associated with an improved outcome. The 2010 ACR/EULAR criteria for RA identify RA patients earlier than the 1987 ACR criteria. Nevertheless, we recently observed that 24% of the 2010 unclassified arthritis (UA) patients develop RA during follow-up. Here we studied this frequency in other cohorts and evaluated the prognostic accuracy of ACPA and the Leiden prediction rule in 2010 UA patients.Methods. The 2010 UA patients from three Early Arthritis Clinics were studied: 776 from Leiden, 121 from Birmingham and 322 from Amsterdam. Fulfilment of the 1987 ACR criteria during follow-up was studied as the primary outcome. DMARD prescription during the year and having a persistent course of arthritis over 7 years were studied as secondary outcomes in one cohort. The presence of ACPA and the prediction score at baseline were evaluated in relation to these outcomes.Results. In the three cohorts, 24%, 26% and 12%, respectively, of the 2010 UA patients fulfilled the 1987 criteria after 1 year. However, some of these patients already fulfilled the 1987 criteria at baseline. In 1987 and 2010 UA patients, 15%, 21% and 9%, respectively, developed RA (1987) at 1 year. In these patients, 0-6% of the patients were ACPA positive and 0-1% had high prediction scores. Consequently a large majority of the UA patients with an unfavourable outcome was not recognized by these prognostic tools.Conclusion. A proportion of 2010 UA patients progress to RA. ACPA and the Leiden prediction rule are not useful in identifying these patients. These results imply that other predictive markers should be developed for 2010 UA patients.
    Rheumatology (Oxford, England) 03/2013; · 4.24 Impact Factor
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    ABSTRACT: OBJECTIVES: Anti-TNF therapies are highly effective in rheumatoid (RA) and psoriatic (PsA) arthritis but a significant number of patients exhibit partial or no therapeutic response. Inflammation alters local and systemic metabolism and TNF plays a role in this. We sought to determine if the patient's metabolic fingerprint prior to therapy could predict responses to anti-TNF agents. METHODS: Urine was collected from 16 RA and 20 PsA patients before and during therapy with infliximab or etanercept. Urine metabolic profiles were assessed using NMR spectroscopy. Discriminating metabolites were identified, and the relationship between metabolic profiles and clinical outcomes was assessed. RESULTS: Baseline urine metabolic profiles discriminated between RA patients who did or did not have a good response to anti-TNF therapy, according to EULAR criteria, with a sensitivity of 88.9% and specificity of 85.7%, with several metabolites (in particular histamine, glutamine, xanthurenic acid and ethanolamine) contributing. There was a correlation between baseline metabolic profiles and the magnitude of change in DAS 28 from baseline to 12 months in RA patients (p=0.04). In both RA and PsA urinary metabolic profiles changed between baseline and 12 weeks of anti-TNF therapy and within the responders, urinary metabolite changes distinguished between etanercept and infliximab treatment. CONCLUSIONS: The clear relationship between urine metabolic profiles of RA patients at baseline and their response to anti-TNF therapy may allow development of novel approaches to the optimisation of therapy. Differences in metabolic profiles during treatment with infliximab and etanercept in RA and PsA may reflect distinct mechanisms of action. © 2013 American College of Rheumatology.
    Arthritis & Rheumatology 03/2013; · 7.48 Impact Factor

Publication Stats

2k Citations
540.44 Total Impact Points

Institutions

  • 1999–2014
    • University of Birmingham
      • • School of Immunity and Infection
      • • Group of Endocrinology, Diabetes and Metabolism
      • • Institute for Biomedical Research
      Birmingham, England, United Kingdom
  • 2010–2013
    • The University of Manchester
      Manchester, England, United Kingdom
  • 2012
    • Keele University
      Newcastle-under-Lyme, England, United Kingdom
  • 2011
    • Sandwell and West Birmingham Hospitals NHS Trust
      Birmingham, England, United Kingdom
  • 2009
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 2008
    • Leiden University Medical Centre
      • Department of Rheumatology
      Leiden, South Holland, Netherlands
  • 1998
    • The Dudley Group NHS Foundation Trust
      Dudley, England, United Kingdom