Sjögren´s Syndrome Research Registry

EU Collaboration

noreply@blogger.com (Sjogren's Registry) — Thu, 07 Feb 2019 11:35:00 +0000

Members of UKPSSR met with their European counterparts to launch an exciting new study into PSS recently at Heathrow Airport. Watch this space!

Fatigue in PSS

noreply@blogger.com (Unknown) — Wed, 30 Jan 2019 16:06:00 +0000

Coming soon to a theatre near you!

We have some interesting data on Fatigue in PSS.

Exciting Collaborations - IMID-Bio UK

noreply@blogger.com (Unknown) — Wed, 30 Jan 2019 15:53:00 +0000

The UKPSSR recently joined forces with the IMID-BIO-UK Partnership.

The goal is to pool information across a range of autoimmune diseases to search for the shared pathways underlying immune-mediated inflammatory diseases.

We will keep you posted as new discoveries emerge.

New extension up to 2019

noreply@blogger.com (Unknown) — Thu, 28 May 2015 14:40:00 +0000

Good news!!

The UKPSSR has been awarded an extension until 2019 – exciting times ahead!!!!!

NHS Choices and Primary Sjogrens Syndrome

noreply@blogger.com (Unknown) — Thu, 13 Nov 2014 14:47:00 +0000

Updated pages on the NHS Choices website:

http://www.nhs.uk/Conditions/Sjogrens-syndrome/Pages/Causes.aspx

Proteins and PSS

noreply@blogger.com (Unknown) — Thu, 23 Jan 2014 07:56:00 +0000

Proteomic analysis of pooled blood serum samples to detect symptom-specific changes in primary Sjögren's Syndrome patients

Katherine James 1,2, Simon J Cockell 3, Colin S Gillespie 4, Anil Wipat 2, Jennifer Hallinan 2, Benedikt M Kessler 5, Roman Fischer 5, Simon J Bowman 6, Bridget Griffiths 7, UKPSSR Study Group 8

1 Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University,

2 School of Computing Science, Newcastle University,

3 Bioinformatics Support Unit, Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, Newcastle University,

4 School of Mathematics and Statistics, Faculty of Science Agriculture and Engineering, Newcastle University,

5 Wellcome Trust Centre for Human Genetics and Henry Wellcome Building for Molecular Physiology, Nuffield Department of Medicine, University of Oxford,

6 Rheumatology Department, University Hospital Birmingham (Selly Oak), Birmingham,

7 Freeman Hospital, Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne,

8 Institute of Cellular Medicine, Newcastle University

Objectives: Primary Sjögren's Syndrome (pSS) is a chronic autoimmune disease characterised by a range of symptoms including dryness, fatigue, depression, anxiety, pain and an increased risk of lymphoma. Patient populations are heterogeneous in their symptoms, making the accurate identification of pSS biomarkers non-trivial. This study aims to identify symptom-specific changes in protein abundance using serum samples from the UK Primary Sjögren's Syndrome Registry (UKPSSR), a cohort of clinically well-characterised pSS patients and healthy controls.

Methods: Patients were chosen from the UKPSSR database and grouped based on their levels of dryness, fatigue, depression, anxiety, and pain. Serum samples from each subject group were pooled and analysed by LC-MS/MS analysis using a Thermo LTQ Orbitrap Velos. Bioinformatic analyses and statistical modelling were then used to characterise the proteins and identify relationships between protein abundance and symptom levels.

Results: A total of 107 proteins were found to have significant changes in abundance between patient groups (ANOVA p>0.05, based on analytical duplicates). The majority of these proteins were immunoglobulins and components of the complement and coagulation cascades. Statistical modelling indicated that several of these abundance changes correlated with symptom levels. In particular, decreases in immunoglobulin chain regions are associated with the high fatigue and high pain groups, while slight decreases in complement components C1R and C4A were associated with dryness.

Conclusions: Differences in blood serum abundance of several proteins can be detected between groups of pSS patients with heterogeneous symptom profiles. These observations suggest that specific proteins may be biomarkers for the individual symptoms of pSS. Future analysis on a patient by patient basis could potentially reveal symptom-specific bio-fingerprints for individual symptom profiles.

Ranked List of Candidate Genes Associated with PSS

noreply@blogger.com (Unknown) — Thu, 23 Jan 2014 07:54:00 +0000

Application of probabilistic functional integrated network analysis to the study of autoimmunity and primary Sjögren's Syndrome

Katherine James 1,2, Jennifer Hallinan 2, Anil Wipat 2, Wan-Fai Ng 1

1 Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University,

2 School of Computing Science, Newcastle University

Objectives: The majority of experimental datasets can be represented as networks of parts and interactions. A network representation allows biological data to be represented in a manner that is both tractable for human visual study and computationally amenable. One of the most powerful approaches to the integration of heterogeneous data is the use of probabilistic functional integrated networks (PFINs), since these networks have statistical weights that indicate the level of confidence in the evidence for each interaction. The confidence weights allow the use of a variety of statistical algorithms that take these weightings into account. This study aims to integrate an immune-specific PFIN from a number of relevant experimental datasets and apply it to the study of primary Sjögren's Syndrome (pSS) and related diseases.

Methods: Functional interaction data were sourced from the BioGRID and InnateDB resources. Datasets were confidence scored using a metabolic pathway Gold Standard dataset derived from the BioSystems Database. The confidence scores were integrated for each individual interaction using a weighted sum. The proteins of the network were then annotated using Gene Ontology biological process terms. Finally, the network was filtered to produce a sub-network of immune proteins and their high confidence interaction partners. The final network was assessed for its ability to predict known autoimmune disease-related proteins before being applied to the prediction of novel pSS-associated proteins and to the comparison of autoimmune diseases using a variety of network analysis techniques.

Results: A probabilistic functional integrated network of immunity was produced. The core immune PFIN contained ˜1700 proteins which were involved in >10,000 interactions. Clustering of the network based on interaction confidence revealed distinct patterns of interaction between pSS-associated proteins and several biological processes, in particular the stress responses. In addition, a ranked list of candidate pSS-associated genes was produced.

Conclusion: Probabilistic network analysis is a powerful approach to data integration and the study of human disease. The immune PFIN generated by this work provides a valuable resource for the future study of pSS and its comparison with other autoimmune diseases.

Integrating Gene Expression and Clinical Data in Sjogren's Syndrome

noreply@blogger.com (Unknown) — Mon, 20 Jan 2014 13:21:00 +0000

Integration of gene expression data with functional interaction and annotation data reveals patterns of connection between pSS-associated genes and the cellular processes in which they are involved

Katherine James 1,2, Jessica R Tarn 1, Shereen Al-Ali 1, Jennifer Hallinan 2, David A Young 1, Wan-Fai Ng 1

1 Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University,

2 School of Computing Science, Newcastle University

Objectives: There is considerable discordance in data from different gene expression studies of primary Sjögren's Syndrome (pSS). Combining these data with other types of information, such as functional interactions and annotation data, can provide a more complete view of the cell in order to identify the key genes and biological pathways that are involved in the disease process of pSS.

Methods: In this study, a list of genes, found to be differentially expressed between pSS patients and controls in four large-scale microarray studies, was derived from the literature. The enrichments of Gene Ontology (GO) biological process annotations for this list were calculated in order to identify those processes that may be involved in pSS pathogenesis.

BioGRID is a comprehensive and highly-curated resource for functional association data generated by multiple experimental techniques. Using BioGRID data, a functional interaction network was generated in which nodes represented genes or gene products, and edges represented any type of BioGRID interaction between the nodes. The network was visualised using the Cytoscape visualisation platform and further annotated based on the Gene Ontology enrichment results. Finally, the network was filtered to produce sub-networks of pSS-associated genes.

Results: Following filtering, a total of 99 of the pSS-associated genes were involved in 111 interactions in the sub-network, the majority of which were connected in one component of 88 genes. All four gene expression datasets were represented within this connected component. Several tight clusters between genes annotated to the processes "innate immune response", "multi-organism process", "response to virus" and "response to stress" were observed in the integrated network. The sub-network also revealed patterns of interaction between these clusters and the pSS-associated genes. In addition, a large number of the pSS-associated genes were found to be annotated to these GO biological processes.

Conclusion: Gene enrichment and network analyses of the pSS-associated genes suggest that the innate immune responses, multi-organism processes, and the responses to virus and to stress are likely to be involved in pSS pathogenesis. Integration of multiple types of data in this manner can aid in the interpretation of results since combining diverse data sources reveals global properties not evident from a single data source. Future studies may benefit from incorporating additional detailed clinical data during the analysis of expression data in order to elucidate the relationship between gene expression and clinical phenotype.

ISSS Abstract: Application of probabilistic functional integrated network analysis to the study of autoimmunity and primary Sjögren's Syndrome

noreply@blogger.com (Sjogren's Registry) — Thu, 28 Nov 2013 12:03:00 +0000

Katherine James, Jennifer Hallinan, Anil Wipat, Wan-Fai Ng

ISSS Abstract: The United Kingdom Primary Sjögren's Syndrome Registry (UKPSSR), a valuable resource for future pSS research

noreply@blogger.com (Sjogren's Registry) — Thu, 28 Nov 2013 12:02:00 +0000

Katherine James, Sheryl Mitchell, Bridget Griffiths, Simon Bowman, Wan-Fai Ng and the UKPSSR Study Group

Objectives: Primary Sjögren's Syndrome (pSS) is the second most common systemic autoimmune disease after rheumatoid arthritis. However, the mechanisms of pSS pathogenesis remain poorly understood. The United Kingdom Primary Sjögren's Syndrome Registry (UKPSSR) aims to facilitate research and improve our understanding of pSS by providing a large cohort of clinically well-characterised pSS patients and matched healthy controls. The project is an initiative of the United Kingdom Sjögren's Interest Group (UKSIG) and is funded by the Medical Research Council.

Methods: PSS patients were recruited from 30 centres across the UK. Extensive subjective and objective clinical data were collected for all patients including demographics, comorbidity, biopsy status, Schirmer's test value and treatment history. Disease activity (ESSDAI, SCAI, SSDAI) and disease damage (SDI, SSDDI) scores were calculated for all patients in the cohort. In addition, patient-reported outcomes were calculated for symptom assessment (PROFAD-SSI, ESSPRI, Epworth sleepiness scale, OGS), quality of life (EQ-5D, SF-36), and, anxiety and depression (HADS). An optional cardiovascular risk assessment was carried out for a subset of the patients. Simultaneously, age-, sex- and ethnicity-matched healthy controls were recruited. Finally, blood samples were bio-banked for all the patients and controls of the cohort.

Results: The UKPSSR is a national cohort and research biobank of approximately 700 clinically well-characterised pSS patients and around 350 matched healthy controls. http://www.sjogrensregistry.org/index.php

Conclusion: The UKPSSR cohort provides a resource to enhance our understanding of pSS through facilitating high-quality clinical and academic research. It is hoped that the UKPSSR will serve as a foundation for the formation of a more extensive collaborative research network for pSS.

ISSS Abstract: Proteomic analysis of pooled blood serum samples to detect symptom-specific changes in primary Sjögren's Syndrome patients

noreply@blogger.com (Sjogren's Registry) — Wed, 27 Nov 2013 13:26:00 +0000

Katherine James, Simon J Cockell, Colin S Gillespie, Anil Wipat, Jennifer Hallinan, Benedikt M Kessler, Roman Fischer, Simon J Bowman, Bridget Griffiths & The UKPSSR Study Group

ISSS Abstract: Integration of gene expression data with functional interaction and annotation data reveals patterns of connection between pSS-associated genes and the cellular processes in which they are involved

noreply@blogger.com (Sjogren's Registry) — Wed, 27 Nov 2013 09:48:00 +0000

Katherine James, Jessica R Tarn, Shereen Al-Ali, Jennifer Hallinan, David A Young, Wan-Fai Ng

ISSS Abstract: Effects of globin mRNA on whole blood gene expression signature in primary Sjögren’s syndrome

noreply@blogger.com (Sjogren's Registry) — Thu, 21 Nov 2013 12:13:00 +0000

Al-Ali S, Cockell S, Tarn JR, James K, Young DA, the UKPSSR study group, Griffiths B, Bowman S, Ng WF

Objectives : Gene expression profiling using peripheral whole blood is a useful approach to identify biomarkers in primary Sjögren's syndrome (PSS). However, using whole blood comes with challenges as a result of the presence of globin mRNA, which represent approximately 70% of the total RNA, potentially reducing the accuracy and sensitivity of microarray analysis. The aim of this study was to evaluate the effect of globin mRNA on whole blood gene expression profiling in PSS .

Methods: Twenty-four peripheral whole blood samples from PSS patients and healthy controls (HC) were used (PSS=12, HC=12) , RNA was extracted according to the PAXgene Blood RNA kit protocol, followed by purification and concentration using the RNeasy MiniElute kit. For each sample, half of the RNA underwent a globin mRNA removal step using the GLOBINclear kit (the "globin-clear group") with the remaining half representing the "globin-present group". The efficiency of globin mRNA clearance was assessed by the ratio of real-time RT-PCR of β-globin mRNA between paired "globin-present" and "globin-clear" samples. Illumina microarrays were performed for all samples and the data analyzed using Genespring GX (Agilent).

Results: b-globin gene expression in 'globin-clear' samples was markedly reduced compared the paired 'globin-present' samples (fold change=139-555) indicating efficient removal of globin mRNA. Consistently, an RNA quality check of the globin-clear samples using a Bioanalyser confirmed lack of a sharp peak of 700 bp which represent the globin mRNA. The Probe intensity signals of the microarray were higher and the quality of the microarray data improved in the 'globin-clear' group. Independent analysis of the 'globin-clear' and the 'globin-present' groups identified 15995 versus 15173 transcripts/entities detectably expressed (1.2-fold p>0.05) between PSS and healthy controls respectively, suggestive of an improvement in the sensitivity of the data after globin-removal. When focussing on those most highly differentially expressed genes (based on relative fold changes), there was significant concurrence between the two methods. Despite the small sample size, the differentially expressed genes identified in this study were similar to a previous report.

Conclusion: Removal of globin mRNA enhanced the quality of the samples and the microarray intensity as well as enhance sensitivity, although there were considerable overlap between the differentially expressed genes identified regardless of whether globin mRNA was removed especially for the genes with high relative levels of expression between PSS and controls.

ISSS Abstract: Whole blood micro RNA signature for primary Sjögren’s syndrome-related lymphoma

noreply@blogger.com (Sjogren's Registry) — Fri, 15 Nov 2013 15:01:00 +0000

Tarn JR, Cockell S, Gillespie C, Al-Ali S, James K, the UK primary Sjögren's syndrome registry, Griffiths B, Bowman S, Young DA, Ng WF

Background: Micro RNAs (miRNAs) are 18-25nt 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 (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 the 'High Function' and 'Lymphoma' patient groups, 44 miRNAs were found to be differentially expressed. The differential expressions of these miRNA were validated by RT-PCR in 3 out of 9 miRNAs with the highest fold-changes between the two groups. Indeed, based on the expression levels of these 3 miRNAs were sufficient to distinguish PSS patients with lymphoma from those without. Two out of these 3 miRNAs were also differentially expressed between the same two groups in the validation cohort.

Conclusion: We have identified 2 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.

NHS: Sjogren's Clinical Trials

noreply@blogger.com (Unknown) — Mon, 11 Nov 2013 14:36:00 +0000

The latest Sjogren's clinical trials on the NHS website.

http://www.nhs.uk/Conditions/Sjogrens-syndrome/Pages/clinical-trial.aspx

National Arthritis Week: Meet the expert.

noreply@blogger.com (Sjogren's Registry) — Mon, 12 Aug 2013 10:00:00 +0000

In preparation for National Arthritis Week a lunch and lecture has been arranged for Monday 7th October at Dobbie's Garden World.

Professor Fai Ng will be present to talk about his research into Sjögren’s syndrome and its relationship to other more 'well known' rheumatic conditions such as rheumatoid arthritis and lupus.

Tickets for the event are £10 and are available from Dobbies Garden World customer service desk, by phone 07905827858 or email c.robertson@arthritisresearchuk.org.

The programme also includes lunch and a donation to Arthritis Research UK, a raffle and a Q&A session. For full details, please see below.

Lunch & Lecture
Monday 7 October 2013 at 11.30am
Recognise and Re-energise – identify the pathways for a better life for primary Sjögren’s syndrome sufferers with Professor Fai Ng.

Dobbies Garden World,
Street House Farm,
Ponteland,
Newcastle-upon-Tyne
NE20 9BT

www.arthritisresearchuk.org

Depression and fatigue are major problems in UK patients with Sjögren’s syndrome – revealed in new health status survey

noreply@blogger.com (Sjogren's Registry) — Mon, 12 Nov 2012 11:05:00 +0000

The annual European League Against Rheumatism (EULAR) 2012 Congress took place in Berlin this year, and among the highlights was the following report on one of the UKPSSR research studies:

The first report on the health problems encountered by patients with primary Sjögren’s syndrome (PSS) indicates a significant burden in terms of impaired health status compared to the UK general population – with depression and fatigue being the key factors.

Presenting the details of a survey involving 620 patients with PSS, Dr Wan-Fai Ng, (Clinical Senior Lecturer, Musculoskeletal Research Group, Institute of Cellular Medicine, University of Newcastle-upon-Tyne) explained that the survey he and his colleagues carried out used EuroQol (EQ)-5D, an increasingly popular health-related quality of life instrument - but which has not until now been applied to patients with PSS.

Dr Ng said that EQ-5D provides a simple descriptive profile, a single index value for health status and a visual analogue score (VAS). “The key advantages of EQ-5D are that the instrument is preference-based, easy to complete and the value sets can be easily converted to quality adjusted life years (QALYs) to aid cost-utility analysis.”

The proportion of PSS patients reporting any problem in mobility (42.4%), self-care (16.9%), usual activities (56.7%), pain/discomfort (81.1%) and anxiety/depression (49.6%) were far higher than in the UK population as a whole (5.4%, 1.6%, 7.9%, 30.2% and 15.7%, respectively).

The mean VAS score in PSS patients was 59.9, compared to 81.3 for the general population, and further analysis showed that EQ-5D VAS correlated with many clinical features of PSS - most strongly with fatigue, depression and pain.

Among the laboratory measures, only immunoglobulin G (IgG) levels, paraproteins and propionylcarnitine (C3) correlated with EQ-5D VAS.

Dr Ng concluded: “Our data adds to the growing body of evidence that effective management of fatigue is key to improving the health status of PSS patients.”

For further information visit http://www.congresscatchup.com/.

Annual BSSA Meeting 2012

noreply@blogger.com (Sjogren's Registry) — Mon, 10 Sep 2012 19:19:00 +0000

Newcastle is fortunate to welcome the Annual General Meeting of the British Sjögren’s Syndrome Association (BSSA) to the world renowned International Centre for Life on 15^th September, where many eminent members of the medical profession will give their time to address those attending the conference. The conference is aimed at both patients, their supporters and allied health care professionals.

Sjögren’s Syndrome is the second most common autoimmune rheumatic disease where the body’s immune system attacks parts of the body instead of fighting infection. In Sjögren’s Syndrome the glands that produce saliva, tears and other secretions become inflamed and as a result can stop working with key symptoms including dry eye and dry mouth. Chronic fatigue can also be a major factor. Sjögren’s Syndrome can strike at any age, but most commonly affects women between the ages of 40 and 60 and 90% of cases are female. Despite being discovered in the early 20^th century by the ophthalmologist Henrik Sjogren, the causes remain unknown with limited treatments available.

The BSSA is a charity dedicated to providing support and information to individuals affected by this disease, as well playing a key role in raising awareness. Support groups operate throughout the UK helping sufferers to cope with the day-to-day challenges of this distressing condition. In addition, Dr Wan-Fai Ng, Newcastle University is the leading researcher for a national registry the ‘United Kingdom Primary Sjögren’s Syndrome Registry’ which is designed to investigate the causes of Sjögren’s syndrome as well as facilitate new clinical trials.

Our local support group the ‘North East Sjögren Support Association’ (NESSA), has over 40 members, and regularly meet at the Freeman Hospital to learn more about this condition as well as to socialise and to support each other. If you wish to know more about NESSA please contact Madge at madge_stokes@hotmail.co.uk .

If you would like further information about the BSSA conference you can email office@bssa.uk.net or telephone Isabel on 0121 4780222.

British Sjogrens Syndrome Awareness - Stephen McPhail

noreply@blogger.com (Sjogren's Registry) — Mon, 10 Sep 2012 19:10:00 +0000

McPhail and Venus hope to increase Sjögren's awareness

noreply@blogger.com (Sjogren's Registry) — Mon, 23 Jul 2012 14:41:00 +0000

In a video interview with Sky Sports, Stephen McPhail has spoken further of his battle with Sjögren's Syndrome and of his relationship with fellow sufferer, tennis star Venus Williams.

The Cardiff City midfielder speaks of his admiration for Williams, who recently returned from a year out with the rheumatoid disease to win the Ladies’ Doubles competition at Wimbledon.

The interview comes in time for World Sjögren's Day and aims to increase awareness of Sjögren's Syndrome.

To watch the interview, click here.

World Sjögren's Day

noreply@blogger.com (Sjogren's Registry) — Mon, 09 Jul 2012 13:10:00 +0000

The Guardian recently published an interesting piece on Sjögren's Syndrome in preparation for its first World Day on the 23^rd July.

The article contains a lot of useful information and website links looking to raise awareness of the rheumatoid disease.

To read the article in full, click here.

UKPSSR: Aims and Objectives

noreply@blogger.com (Sjogren's Registry) — Thu, 17 May 2012 14:45:00 +0000

Want to know more about the UK Primary Sjogren's Syndrome Registry?

Click here to read a presentation outlining the Registry’s aims, objectives and development.

Stephen McPhail talks about his battle with Sjogren’s

noreply@blogger.com (Sjogren's Registry) — Wed, 02 May 2012 11:14:00 +0000

In an ITV article, Cardiff

City midfielder Stephen McPhail has given insight into how he came to terms with Sjogren’s Syndrome. The Republic of Ireland international discusses the affect the condition has had on his personal life and career as a professional footballer.

McPhail, 32, was diagnosed with Sjogren’s only months after recovering from Stage 2 malt lymphoma and is not the only high-profile athlete tormented by the illness. After being forced to withdraw from the US Open last August, it was revealed that tennis star Venus Williams also suffers from the rheumatic disease (see below).

To read the article about Stephen McPhail, click here.

PUBMED Clinical Trials and Sjogren's Syndrome

noreply@blogger.com (Sjogren's Registry) — Thu, 29 Mar 2012 07:23:00 +0000

Useful PUBMED listing of clinical trials reported in the last three years.

Books on Sjögren's Syndrome

noreply@blogger.com (Sjogren's Registry) — Fri, 25 Nov 2011 10:32:00 +0000

Link to Some Books on Sjögren's Syndrome.