Rheumatoid Arthritis: United Kingdom

Scott DL. · King's College School of Medicine, Weston Education Centre, King's College, London, UK. · Best Pract Res Clin Rheumatol. · Pubmed #19233042 No free full text.

Abstract: Most randomized controlled trials (RCTs) investigating the treatment of early rheumatoid arthritis (RA) use the core set of measures proposed by consensus meetings in the 1990s; these include tender and swollen joint counts, pain, global assessments, disability, and acute-phase responders such as the erythrocyte sedimentation rate (ESR). Trials in early RA generally assess three key outcomes based on this core data set: symptoms and signs of inflammatory arthritis, progression of disability, and erosive damage. Adverse events are also recorded. This chapter considers the lessons learned from the various trials in terms of benefits and adverse effects of different treatment regimens.

Young A. · City Hospital, Herts, UK. · Best Pract Res Clin Rheumatol. · Pubmed #19233041 No free full text.

Abstract: Longitudinal and observational studies have provided valuable information on the course, clinical outcomes, and prognostic markers in rheumatoid arthritis (RA). They reflect a complete spectrum of disease in 'true-to-life' settings, and can identify aspects of RA such as long-term outcomes and predictive markers which are not easily obtained from clinical trials. Profiles of drug therapies gained over time from these studies complement those of short-term randomized studies. Comparisons of results from early-RA cohorts show both similarities and considerable differences.

Idris AI. · Bone Research Group, Rheumatic Diseases Unit, University of Edinburgh, General Western Hospital, Edinburgh. · Drug News Perspect. · Pubmed #19221634 No free full text.

Abstract: A number of recent preclinical studies have demonstrated the potential role of cannabinoids and their receptors in bone metabolism. Pharmacological and genetic modulation of cannabinoid receptors indicate that cannabinoid ligands may provide attractive and novel agents for the treatment of bone diseases. This article reviews the role of cannabinoid receptors in regulating bone mass, bone loss and bone cell function in health and disease. The article also provides support to the notion that cannabinoid receptor ligands show a great promise in the treatment of bone diseases associated with accelerated osteoclastic bone resorption including osteoporosis, rheumatoid arthritis and bone metastasis.

Schaschl H, Aitman TJ, Vyse TJ. · Imperial College London, Faculty of Medicine, Section of Molecular Genetics and Rheumatology, Hammersmith Campus, London, UK. · Clin Exp Immunol. · Pubmed #19220326 No free full text.

Abstract: The causes of autoimmune disease remain poorly defined. However, it is known that genetic factors contribute to disease susceptibility. Hitherto, studies have focused upon single nucleotide polymorphisms as both tools for mapping and as probable causal variants. Recent studies, using genome-wide analytical techniques, have revealed that, in the genome, segments of DNA ranging in size from kilobases to megabases can vary in copy number. These changes of DNA copy number represent an important element of genomic polymorphism in humans and in other species and may therefore make a substantial contribution to phenotypic variation and population differentiation. Furthermore, copy number variation (CNV) in genomic regions harbouring dosage-sensitive genes may cause or predispose to a variety of human genetic diseases. Several recent studies have reported an association between CNV and autoimmunity in humans such as systemic lupus, psoriasis, Crohn's disease, rheumatoid arthritis and type 1 diabetes. The use of novel analytical techniques facilitates the study of complex human genomic structures such as CNV, and allows new susceptibility loci for autoimmunity to be found that are not readily mappable by single nucleotide polymorphism-based association analyses alone.

Cohen P. · The MRC Protein Phosphorylation Unit, University of Dundee, The Sir James Black Centre, Dundee, UK. · Curr Opin Cell Biol. · Pubmed #19217767 No free full text.

Abstract: In recent years, protein kinases have become the pharmaceutical industry's most studied class of drug target, and some 10 protein kinase inhibitors have so far been approved for the treatment of cancer. However, whether safe drugs that modulate protein kinase activities can also be developed for the treatment of chronic diseases, where they may need to be taken for decades, is an issue that is still unresolved. A number of compounds that inhibit the p38alpha MAPK have entered clinical trials for the treatment of rheumatoid arthritis and psoriasis, but side effects have prevented their progression to Phase III clinical trials. Here I briefly review the potential problems in targeting p38 MAPK and discuss other protein kinases that regulate the innate immune system, such as Tpl2, MAPKAP-K2/3, MSK1/2 and IRAK4, which may be better targets for the treatment of chronic inflammatory diseases, and NIK, which is an attractive target for the treatment of multiple myeloma, a late stage B-cell malignancy.

Meenagh G, Filippucci E, Delle Sedie A, Riente L, Iagnocco A, Epis O, Scirè CA, Montecucco C, Bombardieri S, Valesini G, Grassi W. · Antrim Hospital, Antrim, United Kingdom. · Clin Exp Rheumatol. · Pubmed #19210859 No free full text.

Abstract: One of the largest challenges to the field of musculoskeletal ultrasonography is attempting to accurately quantify the changes seen in chronic arthritis. With advances in ultrasound technology, researchers have been increasingly exploring ways of more accurately assessing these changes and attempting to reach consensus with agreed scoring systems. This review presents the main scoring systems developed for quantifying sonographic findings indicative of synovitis and joint damage in patients with rheumatoid arthritis. Further investigation is required to attain international consensus on such scoring systems and to evaluate their impact on therapeutic decision-making.

Page TH, Smolinska M, Gillespie J, Urbaniak AM, Foxwell BM. · Kennedy Institute of Rheumatology, Imperial College of Science, Technology and Medicine, 65 Aspenlea Road, London W6 8LH, UK. · Curr Mol Med. · Pubmed #19199943 No free full text.

Abstract: The activity of tyrosine kinases is central to many cellular processes, and accumulating evidence suggests that their role in inflammation is no less profound. Three main tyrosine kinase families, the Src, Tec and Syk kinase families are intimately involved in TLR signalling, the critical first step in cellular recognition of invading pathogens and tissue damage. Their activity results in changes in gene expression in affected cells. Key amongst these genes are the cytokines, which orchestrate both the duration and extent of inflammation. Tyrosine kinases also play important roles in cytokine function, and are implicated in signalling through both pro- and anti-inflammatory cytokines such as TNF, IL-6 and IL-10. Thus, strategies to modulate tyrosine kinase activity have significant therapeutic potential in combating the chronic inflammatory state that is typical of many major health issues that face us today, including Rheumatoid Arthritis, Cardiovascular disease and cancer. Here we review current knowledge of the role of tyrosine kinases in inflammation with particular emphasis on their role in TLR signalling.

Guile SD, Alcaraz L, Birkinshaw TN, Bowers KC, Ebden MR, Furber M, Stocks MJ. · Department of Medicinal Chemistry, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, LE11 5RH, UK. · J Med Chem. · Pubmed #19191585 No free full text.

This publication has no abstract.

Patel VK, Ghosh S. · Gastrointestinal Section, Imperial College London, Hammersmith Hospital, London, U.K. · Drugs Today (Barc). · Pubmed #19180261 No free full text.

Abstract: Certolizumab pegol is a humanized Fab' fragment monoclonal antibody to tumor necrosis factor alpha (TNF-alpha). PEGylation increases its half-life, and it is administered subcutaneously to treat immune-mediated inflammatory diseases such as Crohn's disease and rheumatoid arthritis. Certolizumab pegol improves quality of life and reduces clinical disease activity. Inflammatory markers such as C-reactive protein (CRP) also decrease after administration of certolizumab pegol. The dose for induction of remission is 400 mg subcutaneously at weeks 0, 2 and 4. The dose for maintenance of remission is 400 mg sc given every four weeks. The safety profile is comparable with other anti-TNF agents, and the major adverse events are related to infections. This article reviews the published data regarding the efficacy and safety of certolizumab pegol.

Alavi A, Axford JS. · The Sir Joseph Hotung Centre for Musculoskeletal Diseases, St George University of London, London, UK. · Dis Markers. · Pubmed #19126964 No free full text.

Abstract: Once dismissed as just the icing on the cake, sugar molecules are emerging as vital components in life's intricate machinery. Our understanding of their function within the context of the proteins and lipids to which they are attached has matured rapidly, and with it the far reaching clinical implications are becoming understood. Recent advances in high-throughput glycomic techniques, glyco biomarker profiling, glyco-bioinformatics and development of increasingly sophisticated glyco-arrays, combined with our increased understanding of the molecular details of glycosylation have facilitated the linkage between aberrant glycosylation and human diseases, and highlighted the possibility of using glyco-biomarkers as potential determinants of disease and its progression. The focus of this review is to give an insight into the biological significance of these glycomodifications, highlight some specific examples of glyco-biomarkers in relation to autoimmunity and in particular rheumatoid arthritis, and to explore the exciting possibility of exploiting these for diagnostic and prognostic strategies.

Ernst E. · Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, Exeter EX2 4NT, UK. · BMJ. · Pubmed #19091760 links to  free full text

Abstract: OBJECTIVE: To assess evidence from randomised clinical trials about the effectiveness of extracts of Boswellia serrata (frankincense). DESIGN: Systematic review. DATA SOURCES: Electronic searches on Medline, Embase, Cinahl, Amed, and Cochrane Library. Hand searches of conference proceedings, bibliographies, and departmental files. REVIEW METHODS: All randomised clinical trials of B serrata extract as a treatment for any human medical condition were included and studies of B serrata preparations combined with other ingredients were excluded. Titles and abstracts of all retrieved articles were read and hard copies of all relevant articles were obtained. Selection of studies, data extraction and validation were done by the author. The Jadad score was used to evaluate the methodological quality of all included trials. RESULTS: Of 47 potentially relevant studies, seven met all inclusion criteria (five placebo controlled, two with active controls). The included trials related to asthma, rheumatoid arthritis, Crohn's disease, osteoarthritis, and collagenous colitis. Results of all trials indicated that B serrata extracts were clinically effective. Three studies were of good methodological quality. No serious safety issues were noted. CONCLUSIONS: The evidence for the effectiveness of B serrata extracts is encouraging but not compelling.

Vaidhyanath R, Kirke R, Brown L, Sampath R. · Department of Radiology, University Hospitals of Leicester NHS Trust, Leicester, UK. · Orbit. · Pubmed #19085295 No free full text.

Abstract: A wide range of disease process involve the lacrimal gland/fossa. In this pictorial review, we use histology-proven cases to illustrate conditions that affect the lacrimal gland/fossa. CT and MRI features of neoplastic, inflammatory, infiltrative, and developmental conditions are discussed.

Kelly C, Saravanan V. · Queen Elizabeth Hospital Foundation Trust, Department of Rheumatological Medicine, Sheriff Hill, Gateshead NE9 6SX, UK. · Expert Opin Pharmacother. · Pubmed #19040342 No free full text.

Abstract: This review article describes our present understanding of interstitial lung disease (ILD) complicating rheumatoid arthritis (RA). It discusses its high prevalence and clinical relevance, our recent improvement in understanding both its pathology and physiology, and our expectations of ongoing research into the immunology and genetics of the disease. An important section relates to the effects of drugs routinely used in the treatment of the articular manifestations of RA on the lung, especially in the presence of ILD. The major focus of the article is on therapeutic intervention, and here we discuss traditional and often unsuccessful approaches to treatment, leading on to discuss newly introduced therapeutic options such as anticoagulation and oral N-acetylcysteine. In the later sections, we focus our attention on several promising new therapeutic agents, including mycophenolate and new monoclonal antibody therapies, reviewing the limited literature available to support the use of these agents, concluding with a number of other aspects of treatment that are worthy of consideration.

Magliano M. · Department of Rheumatology, Stoke Mandeville Hospital, Mandeville Road, Aylesbury HP21 8AL, UK. · Menopause Int. · Pubmed #19037063 No free full text.

Abstract: Obesity affects over 20% of the UK's adult population and its prevalence is rising. Obesity can lead to a variety of musculoskeletal problems and is independently associated with locomotor disability and joint pain. Obesity increases the risk of radiographic knee osteoarthritis (OA), but has a lesser effect on disease progression. The association with hip and hand OA is weaker, but implies that excess adipose tissue produces humoral factors, altering articular cartilage metabolism. It has been postulated that the leptin system could be a link between metabolic abnormalities in obesity and increased risk of OA. Although obesity was initially thought to increase the risk of rheumatoid arthritis (RA), further studies showed, that heavier patients with RA have less radiological disease progression and possibly better survival. On the other hand, obesity is strongly associated with hypeuricaemia and gouty arthritis. High body weight correlates independently with metabolic syndrome and may contribute to increased cardiovascular morbidity in patients with gout. Weight reduction should be an important part of treatment for OA and gout. Because obesity at a young age correlates with the development of OA and gout in later life, preventive public health strategies aimed at lowering the incidence of obesity are of most importance.

Buch MH, Vital EM, Emery P. · Academic Unit of Musculoskeletal Disease, University of Leeds, Chapeltown Road, Leeds, LS7 4SA, UK. · Arthritis Res Ther. · Pubmed #19007425 links to  free full text

Abstract: T-cell biology has regained importance in the pathogenesis of rheumatoid arthritis. Despite the significant improvements associated with the introduction of tumor necrosis factor-alpha blockade, reasonable proportions of failures and suboptimal responses have been reported, necessitating a search for alternative targeted therapies. This has included drug therapy designed to interrupt T-cell activation via the co-stimulation pathway. Abatacept is a recombinant fusion protein that blocks the co-stimulatory signal mediated by the CD28-CD80/86 pathway, which is required for T-cell activation. Several clinical trials have confirmed the safety and efficacy of this drug in the treatment of rheumatoid arthritis. This review summarizes the clinical data supporting this line of treatment and considers the safety and efficacy data from phase II and III trials.

Cope AP. · The Kennedy Institute of Rheumatology, Faculty of Medicine, Imperial College London, Aspenlea Road, Hammersmith, London, W6 8LH, UK. · Arthritis Res Ther. · Pubmed #19007421 links to  free full text

Abstract: Over the past decade and a half, advances in our understanding of the pathogenesis of immune-mediated diseases such as rheumatoid arthritis (RA) have translated directly into benefit for patients. Much of this benefit has arisen through the introduction of targeted biological therapies. At the same time, technological advances have made it possible to define, at the cellular and molecular levels, the key pathways that influence the initiation and persistence of chronic inflammatory autoimmune reactions. As our understanding grows, it is likely that this knowledge will be translated into a second generation of biological therapies that are tailor-made for the patient. This review summarizes current perspectives on RA disease pathogenesis, with particular emphasis on what RA T cells look like, what they are likely to see, and how they contribute to persistence of the chronic inflammatory response.

Bowman SJ. · Rheumatology Department, University Hospital Birmingham (Selly Oak), Birmingham B296JD, UK. · Rheum Dis Clin North Am. · Pubmed #18984414 No free full text.

Abstract: The hallmark of Sjögren's syndrome is focal lymphocytic infiltration of exocrine glands leading to mucosal dryness, particularly of the eyes and mouth. In addition, approximately 70% of patients report fatigue as a particularly prominent and disabling feature associated with reduced health-related quality of life. Other key patient-reported extraglandular symptoms include arthralgia, myalgia, and Raynaud's phenomenon. This article reviews these patient-reported features, their relationships with objective assessment of the disease, potential therapies for these symptoms, and how measurements of these symptoms are relevant to outcome assessment in clinical therapeutic trials.

Brennan FM, McInnes IB. · Kennedy Institute of Rheumatology, Imperial College London, London, UK. · J Clin Invest. · Pubmed #18982160 links to  free full text

Abstract: A large number of cytokines are active in the joints of patients with rheumatoid arthritis (RA). It is now clear that these cytokines play a fundamental role in the processes that cause inflammation, articular destruction, and the comorbidities associated with RA. Following the success of TNF-alpha blockade as a treatment for RA, other cytokines now offer alternative targets for therapeutic intervention or might be useful as predictive biomarkers of disease. In this Review, we discuss the biologic contribution and therapeutic potential of the major cytokine families to RA pathology, focusing on molecules contained within the TNF-alpha, IL-1, IL-6, IL-23, and IL-2 families.

Chapman KE, Coutinho AE, Gray M, Gilmour JS, Savill JS, Seckl JR. · Endocrinology Unit, Centre for Cardiovascular Sciences, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. · Mol Cell Endocrinol. · Pubmed #18973788 No free full text.

Abstract: Cortisone, a glucocorticoid hormone, was first used to treat rheumatoid arthritis in humans in the late 1940s, for which Hench, Reichstein and Kendall were awarded a Nobel Prize in 1950 and which led to the discovery of the anti-inflammatory effects of glucocorticoids. To be effective, the intrinsically inert cortisone must be converted to the active glucocorticoid, cortisol, by the intracellular action of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). Whilst orally administered cortisone is rapidly converted to the active hormone, cortisol, by first pass metabolism in the liver, recent work has highlighted an anti-inflammatory role for 11beta-HSD1 within specific tissues, including in leukocytes. Here, we review recent evidence pertaining to the anti-inflammatory role of 11beta-HSD1 and describe how inhibition of 11beta-HSD1, as widely proposed for treatment of metabolic disease, may impact upon inflammation. Finally, the mechanisms that regulate 11beta-HSD1 transcription will be discussed.

Drexler SK, Kong PL, Wales J, Foxwell BM. · Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, 65 Aspenlea Road, Hammersmith, London, W6 8LH, UK. · Arthritis Res Ther. · Pubmed #18947379 links to  free full text

Abstract: Rheumatoid arthritis is a multisystemic auto-inflammatory disease affecting up to 1% of the population and leading to the destruction of the joints. Evidence exists for the involvement of the innate as well as the adaptive immune systems in the pathology of the disease. The success of anti-tumour necrosis factor-alpha indicates the importance of pro-inflammatory mediators produced by innate immune cells in rheumatoid arthritis progression. Therefore, considerable efforts have been made in elucidating the signalling pathways leading to the expression of those mediators. This review will concentrate on the role of signalling pathways in innate immune cells in the context of rheumatoid arthritis.

McGonagle D, Tan AL. · Academic Unit of Musculoskeletal Disease, University of Leeds and Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, UK. · Arthritis Res Ther. · Pubmed #18947372 links to  free full text

Abstract: Modern imaging modalities, including magnetic resonance imaging (MRI), are valuable diagnostic and therapy monitoring tools in rheumatoid arthritis (RA). This article reviewed how these imaging modalities have greatly improved our understanding of pathogenic mechanisms in RA, namely the link between inflammation and damage. For example, traditional paradigms regarding the mechanisms of joint destruction, including the idea that synovitis and damage are uncoupled, have been challenged. As the power of MRI increases, there is a need to define normality since apparently normal joints occasionally exhibit MRI evidence of synovitis in the absence of symptoms.

Wegner N, Wait R, Venables PJ. · Kennedy Institute of Rheumatology Division, Imperial College London, 65 Aspenlea Road, London W6 8LH, UK. · Int J Biochem Cell Biol. · Pubmed #18926919 No free full text.

Abstract: The immune system has evolved to eliminate or inactivate infectious organisms. An inappropriate response against self-components (autoantigens) can result in autoimmune disease. Here we examine the hypothesis that some evolutionarily conserved proteins, present in pathogenic and commensal organisms and their hosts, provide the stimulus that initiates autoimmune disease in susceptible individuals. We focus on seven autoantigens, of which at least four, glutamate decarboxylase, pyruvate dehydrogenase, histidyl-tRNA synthetase and alpha enolase, have orthologs in bacteria. Citrullinated alpha-enolase, a target for autoantibodies in 40% of patients with rheumatoid arthritis, is our main example. The major epitope is highly conserved, with over 90% identity to human in some bacteria. We propose that this reactivity of autoantibodies to shared sequences provides a model of autoimmunity in rheumatoid arthritis, which may well extend to other autoimmune disease in humans.

Calder PC. · Institute of Human Nutrition, School of Medicine, University of Southampton, IDS Building, MP887, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. · Proc Nutr Soc. · Pubmed #18847518 No free full text.

Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease manifested by swollen and painful joints, bone erosion and functional impairment. The joint lesions are characterised by infiltration of T lymphocytes, macrophages and B lymphocytes into the synovium and by synovial inflammation involving eicosanoids, cytokines and matrix metalloproteinases. In relation to inflammatory processes, the main fatty acids of interest are the n-6 PUFA arachidonic acid, which is the precursor of inflammatory eicosanoids such as PGE2 and leukotriene B4, and the n-3 PUFA EPA and DHA, which are found in oily fish and fish oils. Eicosanoids derived from the n-6 PUFA arachidonic acid play a role in RA, and the efficacy of non-steroidal anti-inflammatory drugs in RA indicates the importance of pro-inflammatory cyclooxygenase pathway products of arachidonic acid in the pathophysiology of the disease. EPA and DHA inhibit arachidonic acid metabolism to inflammatory eicosanoids. EPA also gives rise to eicosanoid mediators that are less inflammatory than those produced from arachidonic acid and both EPA and DHA give rise to resolvins that are anti-inflammatory and inflammation resolving. In addition to modifying the lipid mediator profile, n-3 PUFA exert effects on other aspects of immunity relevant to RA such as antigen presentation, T-cell reactivity and inflammatory cytokine production. Fish oil has been shown to slow the development of arthritis in an animal model and to reduce disease severity. Randomised clinical trials have demonstrated a range of clinical benefits in patients with RA that include reducing pain, duration of morning stiffness and use of non-steroidal anti-inflammatory drugs.

Derry S, Barden J, McQuay HJ, Moore RA. · Pain Research and Nuffield Department of Anaesthetics, University of Oxford, West Wing (Level 6), John Radcliffe Hospital, Oxford, Oxfordshire, UK, OX3 9DU. · Cochrane Database Syst Rev. · Pubmed #18843655 No free full text.

Abstract: BACKGROUND: This is an update of a review published in The Cochrane Library, Issue 1, 2003. Celecoxib is a selective cyclo-oxygenase-2 (COX-2) inhibitor prescribed for the relief of chronic pain in osteoarthritis and rheumatoid arthritis. Celecoxib is believed to be associated with fewer upper gastrointestinal adverse effects than conventional non-steroidal anti-inflammatory drugs (NSAIDs). Its effectiveness in acute pain was demonstrated in the earlier review. Additional studies have now been published for the 400 mg dose, and this updated review provides more robust estimates of efficacy and harm. OBJECTIVES: To assess analgesic efficacy and adverse effects of a single oral dose of celecoxib for moderate to severe postoperative pain. SEARCH STRATEGY: Cochrane CENTRAL, MEDLINE, EMBASE, and the Oxford Pain Database. Most recent search: July 2008. SELECTION CRITERIA: Randomised controlled trials (RCTs) of adults prescribed any dose of oral celecoxib or placebo for acute postoperative pain were included. DATA COLLECTION AND ANALYSIS: Eight studies (1380 participants) met the inclusion criteria. Studies were assessed for quality and data extracted by two review authors. Summed pain relief (TOTPAR) or pain intensity difference (SPID) was converted into dichotomous information yielding the number of participants with at least 50% pain relief over four to six hours, and used to calculate the relative benefit (RB) and number-needed-to-treat-to-benefit (NNT) for one patient to achieve at least 50% pain relief with celecoxib who would not have done so with placebo. Information on use of rescue medication was used to calculate the proportion of participants requiring rescue medication and the weighted mean (WM) of the median time to use. MAIN RESULTS: The NNT for celecoxib 200 mg and 400 mg compared with placebo for at least 50% pain relief over four to six hours was 4.2 (CI 3.4 to 5.6) and 2.5 (2.2 to 2.9) respectively. The WM of the median time to use of rescue medication was 6.6 hours with celecoxib 200 mg, 8.4 with celecoxib 400 mg, and 2.3 hours with placebo. The WM proportion of participants requiring rescue medication over 24 hours was 74% with celecoxib 200 mg, 63% for celecoxib 400 mg, and 91% for placebo. The NNT to prevent one patient using rescue medication was 4.8 (3.5 to 7.7) and 3.5 (2.9 to 4.6) for celecoxib 200 mg and 400 mg respectively. One serious adverse event probably related to celecoxib was reported by the trialists. AUTHORS' CONCLUSIONS: Single dose oral celecoxib is an effective means of postoperative pain relief. The 400 mg dose has similar efficacy to ibuprofen 400 mg.

Harrison P, Pointon JJ, Chapman K, Roddam A, Wordsworth BP. · Botnar Research Centre, Nuffield Orthopaedic Centre, Windmill Road, Oxford OX3 7LD, UK. · Rheumatology (Oxford). · Pubmed #18838388 No free full text.

Abstract: OBJECTIVES: IL-1 has a central role mediating inflammation and joint destruction in RA. Single nucleotide polymorphisms (SNPs) and haplotype structure in the promoter region can modulate IL-1 function. This study examined the effects of four common promoter SNPs in the IL-1 region on susceptibility and clinical characteristics of RA in British Caucasian patients and assessed the risk of RA by meta-analysis of published studies. METHODS: Using PCR-based methods, 756 RA patients and 625 healthy controls (HCs) were genotyped for IL-1A (-889 C/A, rs17561), IL-1B (-511 A/G, rs16944), IL-1B (-1464 C/G, rs1143623) and IL-1B (-3737 G/A, rs4848306) SNPs. Further meta-analysis was performed for IL-1B (-511 A/G) incorporating 3712 RA patients and 2331 HC from six association studies. RESULTS: The IL-1B (-1464 C/G) G allele was found to be less common in the RA group [P = 0.01; odds ratio (OR) 1.24; 95% CI 1.04, 1.48]. There was no association between IL-1 SNPs and the presence of HLA-DRB1 shared epitope, RF or clinical characteristics. Meta-analysis revealed statistically significant association between IL-1B (-511 A/G) and RA (P = 0.02; pooled OR 1.13; 95% CI 1.02, 1.26). CONCLUSIONS: There may be a protective effect in RA from the IL-1B (-1464 C/G) G variant. No direct association between the polymorphisms studied and clinical severity characteristics were observed. Further meta-analysis revealed IL-1B (-511 A/G) to be associated with increased susceptibility to RA.