S J Bowman

University Hospitals Birmingham NHS Foundation Trust, Birmingham, England, United Kingdom

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Publications (127)685.41 Total impact

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    ABSTRACT: Primary Sjögren's syndrome (pSS) is a complex autoimmune disease characterised by local exocrine glandular involvement and systemic multiorgan manifestations. In this review we will discuss the value of the histological examination of the salivary glands in the classification criteria, and more recently as prognostic tool for patient stratification and monitoring. The limitations of the current tools used to assess salivary gland pathology in pSS will also be reviewed in relation to using salivary gland biopsy analysis as an outcome measure in clinical trials.
    Schweizerische medizinische Wochenschrift 09/2015; 145:w14168. DOI:10.4414/smw.2015.14168 · 2.09 Impact Factor
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    ABSTRACT: A germline and coding polymorphism (rs2230926) of TNFAIP3 (A20), a central gatekeeper of nuclear factor-kappa B (NF-kB) activation, was recently found associated with primary Sjögren's syndrome (pSS)-associated lymphoma in a French cohort. We aimed to replicate this association. The rs2230926 polymorphism was genotyped in cases and controls of European ancestry from two independent cohorts from UK and France. Case control association tests were performed (Fisher's test) in the two cohorts, followed by a meta-analysis of the two cohorts. The UK cohort included 308 controls and 590 patients with pSS including 31 with a history of lymphoma. The French cohort consisted of 448 controls and 589 patients with pSS including 47 with lymphoma. In both cohorts, the rs2230926 missense polymorphism was not associated with pSS. However, in the UK cohort, the rs2230926G variant was significantly associated with pSS-associated lymphoma (OR=2.74, 95% CI (1.07 to 7.03), p=0.0423, compared with patients with pSS without lymphoma, and OR=3.12, 95% CI (1.16 to 8.41), p=0.0314, compared with healthy controls) as observed in the French cohort. The meta-analysis of the two cohorts confirmed these results (OR=2.48, 95% CI (1.87 to 3.28) p=0.0037 and OR=2.60, 95% CI (1.91 to 3.53) p=0.0031, respectively). This study confirms the role of A20 impairment in pSS-associated lymphoma. Subtle germline abnormalities of genes leading to impaired control of NF-kB activation in B cells continuously stimulated by autoimmunity enhance the risk of lymphoma. 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 09/2015; DOI:10.1136/annrheumdis-2015-207731 · 10.38 Impact Factor
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    ABSTRACT: The series of events leading to tertiary lymphoid organ (TLO) formation in mucosal organs following tissue damage remain unclear. Using a virus-induced model of autoantibody formation in the salivary glands of adult mice, we demonstrate that IL-22 provides a mechanistic link between mucosal infection, B-cell recruitment, and humoral autoimmunity. IL-22 receptor engagement is necessary and sufficient to promote differential expression of chemokine (C-X-C motif) ligand 12 and chemokine (C-X-C motif) ligand 13 in epithelial and fibroblastic stromal cells that, in turn, is pivotal for B-cell recruitment and organization of the TLOs. Accordingly, genetic and therapeutic blockade of IL-22 impairs and reverses TLO formation and autoantibody production. Our work highlights a critical role for IL-22 in TLO-induced pathology and provides a rationale for the use of IL-22-blocking agents in B-cell-mediated autoimmune conditions.
    Proceedings of the National Academy of Sciences 08/2015; 112(35). DOI:10.1073/pnas.1503315112 · 9.67 Impact Factor
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    ABSTRACT: Objective: To reach a European consensus on the definition and characterization of the main organ-specific extraglandular manifestations in primary SS. Methods: The EULAR-SS Task Force Group steering committee agreed to approach SS-related systemic involvement according to the EULAR SS Disease Activity Index (ESSDAI) classification and proposed the preparation of four separate manuscripts: articular, cutaneous, pulmonary and renal ESSDAI involvement; muscular, peripheral nervous system, CNS and haematological ESSDAI involvement; organs not included in the ESSDAI classification; and lymphoproliferative disease. Currently available evidence was obtained by a systematic literature review focused on SS-related systemic features. Results: The following information was summarized for articular, cutaneous, pulmonary and renal involvement: a clear, consensual definition of the clinical feature, a brief epidemiological description including an estimate of the prevalence reported in the main clinical series and a brief list of the key clinical and diagnostic features that could help physicians clearly identify these features. Unfortunately we found that the body of evidence relied predominantly on information retrieved from individual cases, and the scientific information provided was heterogeneous. The analysis of types of involvement was biased due to the unbalanced reporting of severe cases over non-severe cases, although the main sources of bias were the heterogeneous definitions of organ involvement (or even the lack of definition in some studies) and the heterogeneous diagnostic approach used in studies to investigate involvment of each organ. Conclusion: The proposals included in this article are a first step to developing an optimal diagnostic approach to systemic involvement in primary SS and may pave the way for further development of evidence-based diagnostic and therapeutic guidelines.
    Rheumatology (Oxford, England) 07/2015; DOI:10.1093/rheumatology/kev200 · 4.48 Impact Factor
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    ABSTRACT: Background: Many people with primary Sjögren's syndrome (PSS) experience difficulty with participation1. There are currently few published studies of non-pharmacological therapy interventions aiming to improve participation in PSS patients. Group concept mapping is a robust, equitable, and systematic approach which has been successfully utilised to identify priorities in both healthcare and research2. Objectives: To identify priority patient and stakeholder informed intervention targets for a future therapy intervention package which will aim to improve participation in people with PSS. Methods: We conducted a mixed-methods group concept mapping exercise with PSS patients, adult household members (AHM) and health care professionals (HCP) (n=232). Patient and AHM participants were recruited from 12 sites in England and all the patients fulfilled the American European Consensus Group diagnosis criteria. HCP were recruited from across the UK via email distribution lists and at professional meetings. First participants completed a statement generation brainstorming activity to identify key barriers to being able to participate fully in daily activities of their choosing. Next an individual card sorting activity was completed with a refined statement set, where participants each sorted similar meaning statements into groups. Finally each statement was rated for importance on a 1-5 Likert scale. Multi-dimensional scaling and hierarchical cluster analysis statistical techniques were applied to generate concept maps which are a visual representation of all stakeholders' ideas and priorities. The maps depicted the priority themed clusters of ideas and “Go-zones”, or bivariate plots of the priority ratings by group, which pinpoint the priority statements within each cluster. Potential priority therapy intervention targets were subsequently identified. Results: The concept maps revealed 7 key themes: “Symptoms”, “Patient empowerment”, “Access and co-ordination of healthcare”, “Wellbeing”, “Family and friends”, “Knowledge and support” and “Public awareness”. The Symptoms and Patient empowerment clusters received the greater priority ratings. Within these clusters potential priority non-pharmacological intervention therapy targets included fatigue, pain, swallowing, sleep, support to self-manage and adherence to medication.
    European League Against Rheumatism Congress 2015, Rome, Italy; 06/2015
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    ABSTRACT: Background Ultrasonography (US) has been shown to be a sensitive tool to diagnose major salivary gland echotexture abnormalities in primary Sjögren's syndrome (pSS). Objectives The purpose of this study was [1] to assess definitions of the different ultrasonographic components of the salivary glands and [2] to study the reliability of these definitions on static images with an international web exercice. Methods [1]The consensus exercice about definitions was done and discussed between 12 experts on the field of US pSS during 3 annual meetings. All experts were part of the US-pSS study group. [2]Using these preliminary definitions, a reliability exercice was done on static images. A centre (Brest- France) was in charge to send to the participants different representative US images collection of the agreed elementary lesions.30 parotid glands images and 30 submandibular glands images were sent to the experts by mail.They were asked to score each components of each glands in standardized file. Two rounds of exercicewere performed in order to obtain intra and inter reliability. The first round was in January 2014 and the second round was in March 2014. Inter and intra-observer agreements were estimated using the kappa index considering binary variables (agreements are almost perfect k:0.81 to 1.0; substantial: 0.61 to 0.8, moderate: 0.41 to 0.6, fair: 0.21 to 0.4, poor: -1.0 to 0.2). Results All experts were trained for US of salivary gland with at least 5 years of experience. We obtained definitions about 8 different components evaluating the abnormal parenchyma (echogenicity, homogenicity, presence or absence of hyperechoic bands, number of hypoechoic ares, and location of hypoechoic areas, lymph nodes, presence or absence of calcifications, visualisation of posterior border) on salivary glands in pSS patients. Results of the reliability web exercise is shown on table 1. Without practical training session, we showed good results concerning the intra and inter observer reliabilities applying these definitions on US parotid gland and submandibular glands, particularly in taking homogeneity as the main important item in this definition. Reliabilities for calcifications and posterior band were low. Conclusions This is the first consensus-based US definitions on salivary glands and its elementary components. These first results of the reliability exercice on static images without any training showed good results and permit to apply these preliminary definitions in routine practice and for further studies on pSS patients. Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):798.2-798. DOI:10.1136/annrheumdis-2015-eular.3924 · 10.38 Impact Factor
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    ABSTRACT: Background Tertiary lymphoid organs (TLOs) are organized clusters of immune cells that preferentially form in autoimmune diseases such as Sjogren's syndrome (SS). TLOs are believed to contribute to disease progression and lymphoma development in SS. Within TLOs, the ectopic expression of lymphoid chemokines has been shown to correlate with size/degree of organization of the lymphoid aggregates and with the production of autoantibodies (1,2). Recent observational studies in SS have proposed a relationship between IL22 expression, B cell infiltration and humoral autoimmunity (3,4,5), however they failed to provide a molecular mechanism for this relationship. Objectives To investigate the functional role of IL22 in ectopic B cell recruitment and humoral autoimmunity during TLO formation. Methods Inducible mouse model of TLO formation and autoantibody production by retrograde cannulation of the salivary glands with a replication deficient adenovirus (6) was used to assess the role of IL22 in vivo. Salivary glands of C57BL/6 mice (wildtype;WT) and knockout mice (IL22-/-) were cannulated and sacrificed at different time points post cannulation (p.c.) and analysed by immunofluorescence, flow cytometry and RT-PCR. Results Virus cannulation of WT mice salivary glands leads to TLOs formation and autoantibody production. Increased expression of IL22 was found to occur within hours of salivary gland cannulation with different cell populations involved in its production. Surprisingly, Il22-/- mice and WT mice treated therapeutically with anti-IL22 antibody were characterized by profound defects in TLO maturation. Absence or blocking of IL22 impairs CXCL13 and CXCL12 production, resulting in reduced B cell accumulation within the TLOs and abolition of autoantibody production. IL22 exerts a differential effect depending on the target stromal cell in which IL22Rα is expressed. On igp38+ IL22Rα+ stromal cells, IL22 stimulation regulates CXCL13 expression, independently from but also in synergy with, TNFα and LTβ. Conversely, on epithelial cells, IL22Rα engagement increases CXCL12 production but not CXCL13. This effect is direct, as treatment of isolated stromal and epithelial cells with recombinant IL22 in vitro was sufficient to induce CXCL13 and CXCL12 production by gp38+ stromal cells and EPCAM+ epithelial cells respectively. This dual impairment in chemokine expression is responsible for the reduced B cell accumulation, aberrant follicle maturation and lack of autoantibody production observed in both KO and anti-IL22 treated. Conclusions Here we describe for the first time the functional connection between expression of IL22, aberrant chemokine production and autoantibody response in TLO associated autoimmune diseases such as SS. References Disclosure of Interest None declared
    Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):651.2-651. DOI:10.1136/annrheumdis-2015-eular.5049 · 10.38 Impact Factor
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    ABSTRACT: Salivary gland changes, characterised by a focal lymphocytic sialadenitits, play an important role in the diagnosis of primary Sjögren's syndrome (PSS) and were first described over 40 years ago. Recent evidence suggests that minor salivary gland biopsy may also provide information useful for prognostication and stratification, yet difficulties may arise in the histopathological interpretation and scoring, and evidence exists that reporting is variable. With the increasing number of actual and proposed clinical trials in PSS, we review the evidence that might support the role of histopathology as a biomarker for stratification and response to therapy and highlight areas where further validation work is required. 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 06/2015; 74(9). DOI:10.1136/annrheumdis-2015-207499 · 10.38 Impact Factor
  • Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):579.1-579. DOI:10.1136/annrheumdis-2015-eular.5236 · 10.38 Impact Factor
  • 13th International Symposium on Sjögren's Syndrome, Bergen, Norway; 05/2015
  • 13th International Symposium on Sjögren's Syndrome, Bergen, Norway; 05/2015
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    13th International Symposium on Sjogren's syndrome, Bergen, Norway; 05/2015
  • 13th International Symposium on Sjögren's Syndrome, Bergen, Norway; 05/2015
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    ABSTRACT: Background: Several small studies have investigated cognitive impairment in primary SS (PSS) using self-reported measures. We sought to quantify cognitive impairment symptoms in a large cohort of 150 PSS patients compared with controls and to explore the relationship between cognitive impairment with fatigue, pain and mood symptoms. Methods: PSS patients diagnosed according to the American European Consensus Criteria were recruited from 12 sites across the UK. They were invited to complete the Cognitive Failures Questionnaire (CFQ) as well as measures of mood (Hospital Anxiety and Depression Scale), fatigue [visual analogue scale (VAS)], dryness (VAS) and pain (VAS). CFQ scores were compared with data from controls. Completion of the CFQ yields a possible score between 0 and 100, with 0 demonstrating no cognitive symptoms. Results: 150 PSS patients and 198 controls completed the CFQ. An independent samples t-test revealed a statistically significant (P < 0.001) increase in cognitive symptom burden in the patient group [mean score 43.7 (S.D. 17.8)] compared with controls [mean score 35.9 (S.D. 12.9]. This difference persisted (P < 0.001) following analysis of covariance adjusting for age and gender. On average PSS patients scored 8 points higher than controls on the CFQ. This is comparable to data in other fatigued patient groups. There were significant correlations with pain, fatigue, anxiety, depression and subjective dryness scores with CFQ scores. In order to partition the variability in CFQ scores into its component parts, we performed a multiple regression analysis. This confirmed that anxiety was the most important predictor of CFQ scores (P = 0.004). Conclusion: Cognitive impairment is more common in PSS than the general population and people with PSS are likely on average to score 8 points higher on the CFQ. Anxiety is a predictor for cognitive failure in PSS. This work suggests that clinicians need to give consideration to cognitive failure and anxiety in the management of PSS patients. Disclosure statement: The authors have declared no conflicts of interest.
    Rheumatology 04/2015; 54((Suppl 1)):i132. DOI:10.1093/rheumatology/kev089.102 · 4.48 Impact Factor
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    ABSTRACT: Background/Purpose Micro RNAs (miRNAs) are 18–25 nt non-coding RNAs that bind target/complementary sequences within the 3’UTR of RNA molecules steering them towards degradation or translational repression, and play a key role in the regulation of gene expression. Better understanding of the expression pattern of miRNAs in diseases may improve our understanding of the biological basis of the disease and identify potential biomarkers. The role of miRNAs in primary Sjögren’s syndrome (PSS) and PSS-related lymphoma remains poorly understood. The aim of this project is to identify a miRNA signature for PSS-related lymphoma. Methods We profiled the expression of miRNAs in whole blood (PaxGene) total RNA preparations using the Exiqon miRCURY LNA array which encompasses >1400 miRNAs and other small non-coding RNAs. A discovery cohort comprised of 36 samples from the United Kingdom Primary Sjögren’s Syndrome Registry (UKPSSR) (12 PSS patients with lymphoma, 12 PSS patients without lymphoma, 12 healthy controls) were used in the initial analysis. We also explored different normalisation strategies and developed an approach, which we considered most appropriate for analysing these data. Real-Time PCR was used to validate the most highly differentially expressed miRNAs between groups. A miRNA signature for PSS-related lymphoma was identified using cluster analysis followed by validation with a second independent cohort of 36 patients and controls. Results The initial miRNA array profiling revealed a clear clustering of the 3 subject groups. Between patient groups with and without lymphoma association, 44 miRNAs were differentially expressed. RT-PCR was used to validate 3 out of 9 of the most highly differentially expressed miRNAs. A 5-miRNA signature for pSS-associated lymphoma was identified using clustering analysis followed by validation with a second independent cohort of 36 patients and controls. The sensitivity and specificity of the signature is excellent with an area under the ROC curve of 0.92. Conclusion We have identified 5 miRNAs that are differentially expressed in peripheral blood between PSS patients with lymphoma and those without lymphoma. Identifying the mRNA targets of these miRNAs in PSS may improve our understanding of the pathogenesis of PSS-related lymphoma. Furthermore, miRNAs may be useful biomarkers for PSS-related lymphoma.
    Annals of the Rheumatic Diseases 02/2015; 74(Suppl 1):A76-A76. DOI:10.1136/annrheumdis-2015-207259.175 · 10.38 Impact Factor
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    ABSTRACT: To define disease activity levels, minimal clinically important improvement (MCII) and patient-acceptable symptom state (PASS) with the primary Sjögren's syndrome (SS) disease activity indexes: European League Against Rheumatism (EULAR) SS disease activity index (ESSDAI) and EULAR SS patient-reported index (ESSPRI). For 790 patients from two large prospective cohorts, ESSDAI, physician evaluation of disease activity, ESSPRI and patients' satisfaction with their current health status were recorded. Receiver operating characteristic curve analyses and anchoring methods were used to estimate disease activity levels of ESSDAI and the PASS of ESSPRI. At follow-up visit, patients and physicians assessed, respectively, whether symptoms and disease activity have improved or not. An anchoring method based on this evaluation was used to estimate MCII of ESSDAI and ESSPRI. Low-activity (ESSDAI<5), moderate-activity (5≤ESSDAI≤13) and high-activity (ESSDAI≥14) levels were defined. MCII of ESSDAI was defined as an improvement of at least three points. The PASS estimate was defined as an ESSPRI<5 points and MCII as a decrease of at least one point or 15%. This study determined disease activity levels, PASS and MCII of ESSDAI and ESSPRI. These results will help designing future clinical trials in SS. For evaluating systemic complications, the proposal is to include patients with moderate activity (ESSDAI≥5) and define response to treatment as an improvement of ESSDAI at least three points. For addressing patient-reported outcomes, inclusion of patients with unsatisfactory symptom state (ESSPRI≥5) and defining response as an improvement of ESSPRI at least one point or 15% seems reasonable. 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 12/2014; DOI:10.1136/annrheumdis-2014-206008 · 10.38 Impact Factor
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    ABSTRACT: Objective: The aim of this study was to describe the outcomes and predictors for development of damage in a large inception cohort of SLE patients. Methods: This was a prospective longitudinal study of a cohort of SLE patients. SLE patients were included if they were recruited within 3 years of achieving the fourth ACR criterion for SLE. Data were collected on disease activity, damage and treatment. Information on death was provided by the Office for National Statistics. The censoring date for analysis was 31 December 2010. A standardized mortality ratio was calculated. Poisson regression was used to determine the incidence rate for damage accrual. Multistate Markov modelling was used to determine predictors for development of damage. Results: There were 382 patients (92.4% females, 51.6% Caucasian, 22% South Asian, 20.7% Afro-Caribbean) with 12 072 assessments and total follow-up of 2958 patient-years. There were 300 items of damage (in 143 patients) and 37 deaths. The overall standardized mortality ratio was 2.0 (95% CI 1.5, 2.8) and the most common causes of death were infection (37.8%), cardiovascular (27%) and malignancy (13.5%). The predictors for damage accrual were higher prior damage, older age at diagnosis, active disease, systemic corticosteroid exposure and CYC exposure. Patients were more likely to develop new damage earlier in their disease than later. Ethnicity was not predictive of damage accrual or death in this cohort. Conclusion: SLE patients have premature mortality. Active disease, corticosteroid exposure and CYC exposure were independently associated with the development of damage. Damage accrual is more likely to occur in early disease.
    Rheumatology 10/2014; 54(5). DOI:10.1093/rheumatology/keu412 · 4.48 Impact Factor
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    ABSTRACT: Objective: This study sets out to investigate the relationship between health status [EuroQol five-dimensions questionnaire (EQ-5D)] in primary SS and three of the European League Against Rheumatism (EULAR) SS outcome measures-the disease activity index (ESSDAI), the patient reported index (ESSPRI) and the sicca score. In particular, the goal was to establish whether there is a relationship between the EULAR outcome measures and quality of life. Methods: Health status was evaluated using a standardized measure developed by the EuroQol Group-the EQ5D. This permits calculation of two measures of health status: time trade-off (TTO) values and the EQ-5D visual analogue scale (VAS) scores. We used Spearman's rank correlation analysis to investigate the strength of association between health status and three EULAR measures of physician- and patient-reported disease activity in 639 patients from the UK primary SS registry (UKPSSR) cohort. Results: This study demonstrates that the EULAR SS disease-specific outcome measures are significantly correlated with health outcome values (P < 0.001). Higher scores on the ESSDAI, EULAR sicca score and ESSPRI are associated with poorer health states-i.e. lower TTO values and lower VAS scores. While all three are significantly correlated with TTO values and EQ-5D VAS scores, the effect is strongest for the ESSPRI. Conclusion: This study provides further evidence supporting the use of ESSDAI, EULAR sicca score and ESSPRI measures in the clinic. We also discuss the need for disease-specific measures of health status and their comparison with standardized health outcome measures.
    Rheumatology (Oxford, England) 09/2014; 54(4). DOI:10.1093/rheumatology/keu361 · 4.48 Impact Factor
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    ABSTRACT: Objective: Human endogenous retrovirus (HERV)-K10 has been implicated in the etiology and pathogenesis of rheumatoid arthritis (RA). A secondary immune response to this virus might suggest an antigen-driven response in patients. The Gag region of HERV-K10 could provide a key epitope important for immunological reactivity. We investigated the presence of IgG antibodies to this region and assessed its significance in RA. Methods: We determined an antigenic peptide on the matrix segment of HERV-K10 and developed an ELISA system to detect IgG antibodies in patients with RA and controls. The presence of antibodies to the matrix peptide (denoted as MAG1: RIGKELKQAGRKGNI) was correlated with patient details. Results: On screening patients' serum, we found a significantly higher mean IgG antibody response to MAG1 in 30 patients with RA as compared to 23 patients with inflammatory bowel disease (p = 0.003), 29 patients with osteoarthritis (p = 0.001), and 43 healthy individuals (p = 0.002). Reactivity was not observed to a control peptide possessing a nonhomologous amino acid sequence. On evaluating clinical details with serological activity, no correlation with disease duration (p = 0.128), sex (p = 0.768), or rheumatoid factor status (p = 0.576) was found. Conclusion: A significantly elevated IgG antibody response to an HERV-K10 Gag matrix peptide was observed in patients with RA, suggesting that the exposure of HERV-K10 may cause a secondary, antigenic driven immune response in RA.
    The Journal of Rheumatology 09/2014; 41(10). DOI:10.3899/jrheum.130502 · 3.19 Impact Factor
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    ABSTRACT: Background There is an inconsistent relationship between subjective symptoms and objective markers of disease activity in individuals with Primary Sjögren's Syndrome (PSS). This presents a significant barrier to developing treatments if modifying disease markers does not translate into lower perceived symptoms. Little is known about the reasons for this discrepancy. Objectives To identify subgroups of PSS patients that vary in the correspondence between subjective symptoms and objective levels of illness. Methods The UK Primary Sjögren's Syndrome Registry (n=688) was used. Measures included subjective ocular and oral dryness, objective tear and saliva production, depression and anxiety (HADS), pain, fatigue and quality of life (EQ 5D TTO). Patients were divided into the top and bottom 30th percentiles on subjective and objective dryness and classed as “high” or “low” (middle scorers disregarded). Four groups were derived – Accurate Severe (high perceived dryness, low tear/saliva production), Accurate Mild (low perceived dryness, high tear/saliva production), Stoic (low perceived dryness, low tear/saliva production) and Sensitive (high perceived dryness, high tear/saliva production). The groups were compared on measures of mood, anxiety, pain, fatigue and quality of life. Results Data from the classification based on ocular dryness are reported. There were: 55 Sensitive, 71 Accurate Severe, 85 Accurate Mild and 59 Stoic. On all measures, the Sensitive group rated themselves as having worse symptoms and poorer functioning, followed in order by the Accurate Severe group, the Accurate Mild group, and the Stoic group. Comparing the groups using ANOVA with follow-up comparisons indicated no statistically significant differences between the Sensitive and the Accurate Severe groups (all p>0.39), except for pain – the Sensitive group reported significantly higher pain than the Accurate Severe group (p=0.02). The Sensitive group rated themselves significantly worse on all measures compared to the Accurate Mild and Stoic groups (all p<0.001). The Stoic group rated themselves significantly better on all measures than the Sensitive and Accurate Severe groups (all p<0.04). The Stoic group rated themselves significantly less fatigued than the Accurate Mild group (p<0.03). Overall a very similar pattern was noted for oral dryness. Conclusions Subgroups were identified based on the correspondence between subjective symptoms and objective illness markers. Patients whose perceived dryness was higher than would be anticipated from objective measurements reported the highest level of symptoms on all measures and the poorest quality of life. The opposite was the case for those whose subjective symptoms were lower than their objective illness markers would indicate. Although objective measures are subject to several confounds, nonetheless these findings suggest further investigation of these groups, exploring biological and psychological factors that may relate to symptom sensitisation, could be of significant value in elucidating our understanding of the path from symptom to distress and disability. This may ultimately guide intervention strategies. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.2464
    Annals of the Rheumatic Diseases 06/2014; 73:Suppl 2(Suppl 2):188-189. DOI:10.1136/annrheumdis-2014-eular.2464 · 10.38 Impact Factor

Publication Stats

2k Citations
685.41 Total Impact Points


  • 2005–2015
    • University Hospitals Birmingham NHS Foundation Trust
      Birmingham, England, United Kingdom
    • National Institutes of Health
      Maryland, United States
  • 2002–2015
    • University of Birmingham
      • • MRC Centre for Immune Regulation
      • • School of Psychology
      • • School of Immunity and Infection
      Birmingham, England, United Kingdom
  • 2012–2014
    • Newcastle University
      • Institute of Cellular Medicine
      Newcastle-on-Tyne, England, United Kingdom
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 2012–2013
    • The Queen Elizabeth Hospital
      Tarndarnya, South Australia, Australia
  • 2007
    • University of Aberdeen
      Aberdeen, Scotland, United Kingdom
  • 2006
    • University of Wolverhampton
      Wolverhampton, England, United Kingdom
  • 2001
    • Sapienza University of Rome
      • Department of Experimental Medicine
      Roma, Latium, Italy
    • Birmingham and Solihull Mental Health NHS Foundation Trust
      Birmingham, England, United Kingdom
  • 1999
    • Sandwell and West Birmingham Hospitals NHS Trust
      Birmingham, England, United Kingdom