Karim Raza

Queen Elizabeth Hospital Birmingham, Birmingham, England, United Kingdom

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Publications (132)741.31 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: During an inflammatory response, lymphocyte recruitment into tissue must be tightly controlled because dysregulated trafficking contributes to the pathogenesis of chronic disease. Here we show that during inflammation and in response to adiponectin, B cells tonically inhibit T cell trafficking by secreting a peptide (PEPITEM) proteolytically derived from 14.3.3 zeta delta (14.3.3.ζδ) protein. PEPITEM binds cadherin-15 on endothelial cells, promoting synthesis and release of sphingosine-1 phosphate, which inhibits trafficking of T cells without affecting recruitment of other leukocytes. Expression of adiponectin receptors on B cells and adiponectin-induced PEPITEM secretion wanes with age, implying immune senescence of the pathway. Additionally, these changes are evident in individuals with type 1 diabetes or rheumatoid arthritis, and circulating PEPITEM in patient serum is reduced compared to that of healthy age-matched donors. In both diseases, tonic inhibition of T cell trafficking across inflamed endothelium is lost. Control of patient T cell trafficking is re-established by treatment with exogenous PEPITEM. Moreover, in animal models of peritonitis, hepatic ischemia-reperfusion injury, Salmonella infection, uveitis and Sjögren's syndrome, PEPITEM reduced T cell recruitment into inflamed tissues.
    Nature medicine 04/2015; DOI:10.1038/nm.3842 · 28.05 Impact Factor
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    ABSTRACT: There is currently no biochemical test for detection of early-stage osteoarthritis (eOA). Tests for early-stage rheumatoid arthritis (eRA) such as rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies require refinement to improve clinical utility. We developed robust mass spectrometric methods to quantify citrullinated protein (CP) and free hydroxyproline in body fluids. We detected CP in the plasma of healthy subjects and surprisingly found that CP was increased in both patients with eOA and eRA whereas anti-CCP antibodies were predominantly present in eRA. A 4-class diagnostic algorithm combining plasma/serum CP, anti-CCP antibody and hydroxyproline applied to a cohort gave specific and sensitive detection and discrimination of eOA, eRA, other non-RA inflammatory joint diseases and good skeletal health. This provides a first-in-class plasma/serum-based biochemical assay for diagnosis and type discrimination of early-stage arthritis to facilitate improved treatment and patient outcomes, exploiting citrullinated protein and related differential autoimmunity.
    Scientific Reports 03/2015; 5:9259. DOI:10.1038/srep09259 · 5.08 Impact Factor
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    ABSTRACT: Rheumatoid arthritis (RA) is a heterogeneous chronic immune-mediated inflammatory disease, associated with significant morbidity and reduced life expectancy. Here, we review recent discoveries; particularly those which have attempted to integrate genome-wide association studies (GWAS) with biological pathways and cell types known to play a role in disease pathology in order to expand our current understanding of the pathogenesis of RA. As the role of stromal cells in the pathogenesis of RA has been reviewed in detail in Current Opinions in Rheumatology, this area will not be covered in this review. Although our understandings of the pathogenic processes that drive disease in RA remain incomplete, remarkable advances over the past year can be highlighted. GWAS have raised awareness of important new risk loci with genes that either are the targets of approved therapies for RA, or involve pathways for drugs that could be repurposed from other disease indications such as cancer. Furthermore, promising strides have been made in predicting the likelihood of developing RA in those at risk using human leukocyte antigen (HLA), smoking, and autoantibody status prediction models. These findings give a fresh insight into RA pathogenesis and help identify new, or repurpose known therapeutic targets from other disease areas. The findings discussed in this review underscore the progress made to date and the need for future studies, investigating disease mechanisms in RA, with particular interest in at-risk RA gene loci, their function in immune and stromal cells within the synovium, and how they interact with environmental factors to initiate and perpetuate disease.
  • Karim Raza, Andrew Filer
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    ABSTRACT: For our understanding of the pathogenesis of rheumatoid arthritis (RA), it is important to elucidate the mechanisms underlying early stages of synovitis. Here, synovial cytokine production was investigated in patients with very early arthritis. Synovial biopsies were obtained from patients with at least one clinically swollen joint within 12 weeks of symptom onset. At an 18-month follow-up visit, patients who went on to develop RA, or whose arthritis spontaneously resolved, were identified. Biopsies were also obtained from patients with RA with longer symptom duration (>12 weeks) and individuals with no clinically apparent inflammation. Synovial mRNA expression of 117 cytokines was quantified using PCR techniques and analysed using standard and novel methods of data analysis. Synovial tissue sections were stained for CXCL4, CXCL7, CD41, CD68 and von Willebrand factor. A machine learning approach identified expression of mRNA for CXCL4 and CXCL7 as potentially important in the classification of early RA versus resolving arthritis. mRNA levels for these chemokines were significantly elevated in patients with early RA compared with uninflamed controls. Significantly increased CXCL4 and CXCL7 protein expression was observed in patients with early RA compared with those with resolving arthritis or longer established disease. CXCL4 and CXCL7 co-localised with blood vessels, platelets and CD68(+) macrophages. Extravascular CXCL7 expression was significantly higher in patients with very early RA compared with longer duration RA or resolving arthritis CONCLUSIONS: Taken together, these observations suggest a transient increase in synovial CXCL4 and CXCL7 levels in early RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Annals of the Rheumatic Diseases 03/2015; DOI:10.1136/annrheumdis-2014-206921 · 9.27 Impact Factor
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    ABSTRACT: To explore how social interactions at the onset of rheumatoid arthritis (RA) influence help-seeking behaviour from the perspectives of those with RA and their significant others (family and friends). Nineteen semi-structured qualitative interviews were undertaken with people recently diagnosed with RA and their significant others. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Significant others' initial appraisals of symptoms led them to provide practical support with daily activities rather than advice to seek help. People with RA described difficulties in communicating the severity of their symptoms and often attempted to hide their symptoms from others. Significant others also reacted negatively, expressing disbelief and dismissing symptoms. On occasion, early symptoms were even described as the catalyst for the breakdown of relationships. On reflection, significant others expressed guilt about their initial reactions and wished that they had recognized the need for intervention earlier. When symptoms had advanced and were more obvious, significant others often strongly advised that help should be sought and, in some cases, physically escorted the patient to their medical appointment. In many instances, people with RA described significant others as the catalyst for eventually seeking help. Significant others play an important role in influencing help-seeking behaviour; this has implications for theoretical models of help-seeking and the development of help-seeking interventions. A negative consequence of social interactions resulted from a lack of understanding and knowledge about RA among significant others, highlighting the need for greater public awareness about the early symptoms of RA. Statement of contribution What is already known on this subject? At the onset of rheumatoid arthritis (RA) people often delay in seeking help, leading to poor clinical outcomes. Previous research has highlighted the role of personal interpretations of symptoms in help seeking. However, little is known about the social context of help-seeking decisions and role of social networks in influencing help-seeking behaviour. What this study adds? This study highlights the importance of social interactions at the onset on RA from multiple perspectives (i.e., those with RA, their family and friends) Family and friends played a critical role at symptom onset, and help-seeking was found to be both facilitated and hindered by social networks. It is vital that help-seeking campaigns and theoretical models give more weight to the role of social interactions in encouraging help-seeking behaviour. © 2015 The British Psychological Society.
    British Journal of Health Psychology 02/2015; DOI:10.1111/bjhp.12134 · 2.70 Impact Factor
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    ABSTRACT: Treating patients with rheumatoid arthritis (RA) within 3 months of symptom onset leads to significantly improved clinical outcomes. However, many people with RA symptoms wait a long time before seeking medical attention. To develop effective health interventions to encourage people to seek help early, it is important to understand what the general public knows about RA, how they would react to the symptoms of RA, and what might delay help-seeking. Qualitative interviews were conducted with 38 members of the general public (32 women) without any form of inflammatory arthritis about their perceptions of RA symptoms and decisions to seek help were they to experience such symptoms. The interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis. A number of barriers and drivers to help-seeking were identified and grouped into 5 themes: perceived causes of symptoms; factors related to presentation, location, and experience of symptoms; perceived effect of symptoms on daily life; self-management of symptoms; and general practitioner-related drivers and barriers. To our knowledge, our study is the first to investigate barriers to and drivers of help-seeking in response to the onset of RA symptoms in individuals without a diagnosis of RA. It has revealed a number of additional factors (e.g., the importance of the location of the symptoms) besides those previously identified in retrospective studies of patients with RA. Together with the data from previous research, these findings will help inform future health interventions aimed at increasing knowledge of RA and encouraging help-seeking.
    The Journal of Rheumatology 02/2015; DOI:10.3899/jrheum.140913 · 3.17 Impact Factor
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    ABSTRACT: Synovial fibroblasts in persistent inflammatory arthritis have been suggested to have parallels with cancer growth and wound healing, both of which involve a stereotypical serum response programme. We tested the hypothesis that a serum response programme can be used to classify diseased tissues, and investigated the serum response programme in fibroblasts from multiple anatomical sites and two diseases. To test our hypothesis we utilized a bioinformatics approach to explore a publicly available microarray dataset including rheumatoid arthritis (RA), osteoarthritis (OA) and normal synovial tissue, then extended those findings in a new microarray dataset representing matched synovial, bone marrow and skin fibroblasts cultured from RA and OA patients undergoing arthroplasty. The classical fibroblast serum response programme discretely classified RA, OA and normal synovial tissues. Analysis of low and high serum treated fibroblast microarray data revealed a hierarchy of control, with anatomical site the most powerful classifier followed by response to serum and then disease. In contrast to skin and bone marrow fibroblasts, exposure of synovial fibroblasts to serum led to convergence of RA and OA expression profiles. Pathway analysis revealed three inter-linked gene networks characterising OA synovial fibroblasts: Cell remodelling through insulin-like growth factors, differentiation and angiogenesis through _3 integrin, and regulation of apoptosis through CD44. We have demonstrated that Fibroblast serum response signatures define disease at the tissue level, and that an OA specific, serum dependent repression of genes involved in cell adhesion, extracellular matrix remodelling and apoptosis is a critical discriminator between cultured OA and RA synovial fibroblasts.
    PLoS ONE 01/2015; 10(3):e0120917. DOI:10.1371/journal.pone.0120917 · 3.53 Impact Factor
  • Karim Raza, Danielle M. Gerlag
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    ABSTRACT: Chronic inflammatory and autoimmune conditions result from an interplay between genetic and environmental factors culminating in the phenotypes of established disease. The transition from health to established disease is relatively well understood in rheumatoid arthritis (RA), which provides an exemplar for other diseases. This article addresses terminologies to describe the phases of disease leading to RA, disease initiation and the point from which disease duration should be timed, the future research agenda suggested by this approach to the definition of phases of disease, and the importance of capturing the patient perspective in research into the earliest phases of disease. Copyright © 2014 Elsevier Inc. All rights reserved.
    Rheumatic Disease Clinics of North America 11/2014; 40(4). DOI:10.1016/j.rdc.2014.07.001 · 1.74 Impact Factor
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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; · 2.97 Impact Factor
  • Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):1191-1191. DOI:10.1136/annrheumdis-2014-eular.4424 · 9.27 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; DOI:10.1111/hex.12203 · 2.85 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; DOI:10.1093/rheumatology/keu159 · 4.44 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. DOI:10.1136/annrheumdis-2013-205124.29 · 9.27 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; DOI:10.1111/nyas.12389 · 4.31 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. DOI:10.1136/annrheumdis-2013-205124.43 · 9.27 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. DOI:10.1136/annrheumdis-2013-205124.52 · 9.27 Impact Factor
  • 03/2014; DOI:10.1530/endoabs.34.P368
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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. DOI:10.1136/annrheumdis-2013-205124.65 · 9.27 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. DOI:10.3109/02813432.2014.900239 · 1.61 Impact Factor

Publication Stats

2k Citations
741.31 Total Impact Points

Institutions

  • 2015
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 2002–2015
    • University of Birmingham
      • • School of Immunity and Infection
      • • MRC Centre for Immune Regulation
      • • Institute for Biomedical Research
      Birmingham, England, United Kingdom
  • 2006–2013
    • Sandwell and West Birmingham Hospitals NHS Trust
      Birmingham, England, United Kingdom
  • 2012
    • Keele University
      Newcastle-under-Lyme, England, United Kingdom
    • University of Amsterdam
      • Faculty of Medicine AMC
      Amsterdamo, North Holland, Netherlands
  • 2008
    • Leiden University Medical Centre
      • Department of Rheumatology
      Leiden, South Holland, Netherlands
  • 1998
    • The Dudley Group NHS Foundation Trust
      Dudley, England, United Kingdom