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1.  Challenges in understanding Sjögren's syndrome - improved insights into the pathogenesis generate hope for innovative therapies? 
The reviews in this series on Sjögren syndrome provide an up-to-date summary and perspectives on the pathogenesis of this interesting entity with glandular and frequently systemic manifestations, the value of preclinical models, and our current understanding of therapeutic approaches. The last of these includes what has been learned from trials blocking tumor necrosis factor and, more recently, anti-CD20 therapy. Potential therapeutic targets, such as blockade of the B cell-activating factor, the role of interferon-alpha, and targeting CD22, are discussed.
PMCID: PMC3239360  PMID: 21888689
2.  T cells as key players for bone destruction in gouty arthritis? 
The deposition of monosodium urate (MSU) crystals in synovial fluid and tissue leads to gouty arthritis frequently associated with synovial inflammation and bone erosions. The cellular mechanism that links MSU crystals to an increased number of osteoclasts has not yet been fully understood. In a recent issue of Arthritis Research & Therapy Lee and colleagues proposed that bone destruction in chronic gouty arthritis is at least in part dependent on expression by T cells of receptor activator of NF-κB ligand (RANKL). The authors showed that pro-resorptive cytokines such as IL-1β, IL-6, and TNFα are expressed within tophi and stromal infiltrates. In vitro stimulation with MSU crystals revealed monocytes as a source for these cytokines, whereas T cells produce RANKL, the major trigger of osteoclastogenesis.
PMCID: PMC3334629  PMID: 22136246
3.  The new era of autoimmune disease research 
Recent genome-wide association studies have advanced our understanding of genetic factors that underlie systemic lupus erythematosus (SLE), a multifactorial autoimmune disease characterized by various clinical manifestations. SLE also has an environmental component, which can trigger or exacerbate the disease. Despite extensive efforts aimed at elucidating the cellular and biological abnormalities that arise in the immune system of patients with SLE, its pathology remains unclear. Lee and colleagues recently carried out gene expression profiling of patients with SLE followed by bioinformatics analysis and discovered the existence of abnormal regulatory networks and potential key molecules. The authors found that ATP synthesis and DNA repair pathways may be involved in the pathogenesis, providing a potential explanation for photosensitivity experienced by patients with SLE.
PMCID: PMC3218883  PMID: 21639950
4.  Nordic walking in fibromyalgia: a means of promoting fitness that is easy for busy clinicians to recommend 
A total of 67 women with fibromyalgia were recruited to an exercise study and were randomized to moderate-to-high-intensity Nordic walking (age 48 ± 7.8 years) or to a control group engaging in supervised low-intensity walking (age 50 ± 7.6 years). A total of 58 patients completed. Significantly greater improvement in the 6-minute walk test was found in the Nordic walking group (P = 0.009), compared with the low-intensity walking group. A significantly larger decrease in exercise heart rate (P = 0.020) and significantly improved scores on the Fibromyalgia Impact Questionnaire Physical function (P = 0.027) were found in the Nordic walking group as compared with the low-intensity walking group. No between-group difference was found for the Fibromyalgia Impact Questionnaire total or pain scores. The authors conclude that moderate-to-high intensity aerobic exercise by means of Nordic walking twice a week for 15 weeks was found to be a feasible mode of exercise, resulting in improved functional capacity and a decreased level of activity limitations.
PMCID: PMC3157638  PMID: 21345243
6.  IL-21 and Sjögren's syndrome 
Treatment of Sjögren's syndrome is almost entirely symptomatic. A lack of true understanding of the underlying immunological pathology of the disease prevents directed therapy. Interleukin-21 (IL-21) is elevated in the serum of patients with this disease and is expressed by the lymphocytes infiltrating the salivary glands. The known functions of IL-21 in facilitating differentiation, proliferation, and survival of both B and T cells mesh well with the findings in Sjögren's syndrome. Demonstration of IL-21 as a fundamental aspect of the pathophysiology of Sjögren's syndrome could lead to the development of anti-IL-21 therapy for this disease.
PMCID: PMC3334639  PMID: 22226370
7.  Beyond cognitive-behavioral therapy for fibromyalgia: addressing stress by emotional exposure, processing, and resolution 
I comment on the well-designed trial by Alda and colleagues reported in a recent issue of Arthritis Research and Therapy which demonstrated some benefits of cognitive-behavioral therapy (CBT) for fibromyalgia (FM). CBT in this and other studies provides statistically significant but rather modest benefits for FM. This may be because CBT does not directly address the high rates of victimization, post-traumatic stress disorder, and emotional avoidance experienced by a substantial number of patients with FM. Interventions that encourage emotional exposure, processing, and resolution of stressful or traumatic experiences and relationships hold potential for larger effects for many patients and need to be tested.
PMCID: PMC3334632  PMID: 22132710
8.  Central pain contributions in osteoarthritis: next steps for improving recognition and treatment? 
There is increasing recognition that central pain sensitivity plays an important role in pain severity among patients with osteoarthritis. Murphy and colleagues identified clusters of patients with osteoarthritis according to pain severity and accompanying symptoms, and one of these groups appeared to have a greater degree of centrally mediated pain. This observation provides some evidence that patients with greater central pain contributions can be identified in routine clinical settings, but brief, evidence-based strategies are still needed to more readily and systematically identify these patients. There is also a need to develop new strategies and to further evaluate existing therapies (pharmacological and nonpharmacological) that target central aspects of osteoarthritis pain.
PMCID: PMC3334627  PMID: 22136200
11.  Type I interferon pathway in adult and juvenile dermatomyositis 
Gene expression profiling and protein studies of the type I interferon pathway have revealed important insights into the disease process in adult and juvenile dermatomyositis. The most prominent and consistent feature has been a characteristic whole blood gene signature indicating upregulation of the type I interferon pathway. Upregulation of the type I interferon protein signature has added additional markers of disease activity and insight into the pathogenesis of the disease.
PMCID: PMC3334651  PMID: 22192711
12.  Mechanisms of tissue injury in lupus nephritis 
Systemic lupus erythematosus is a prototypic autoimmune disease characterized by autoantibody production and immune complex formation/deposition in target organs such as the kidney. Resultant local inflammation then leads to organ damage. Nephritis, a major cause of morbidity and mortality in patients with lupus, occurs in approximately 50% of lupus patients. In the present review, we provide an overview of the current research and knowledge concerning mechanisms of renal injury in both lupus-prone mouse models and human lupus patients.
PMCID: PMC3334648  PMID: 22192660
13.  The 2011 ACR Meeting: what's new in the Windy City 
PMCID: PMC3334652  PMID: 22192758
14.  Imaging modalities in hand osteoarthritis - status and perspectives of conventional radiography, magnetic resonance imaging, and ultrasonography 
Hand osteoarthritis (OA) is very frequent in middle-aged and older women and men in the general population. Currently, owing to high feasibility and low costs, conventional radiography (CR) is the method of choice for evaluation of hand OA. CR provides a two-dimensional picture of bony changes, such as osteophytes, erosions, cysts, and sclerosis, and joint space narrowing as an indirect measure of cartilage loss. There are several standardized scoring methods for evaluation of radiographic hand OA. The scales have shown similar reliability, validity, and sensitivity to change, and no conclusion about the preferred instrument has been drawn. Patients with hand OA may experience pain, stiffness, and physical disability, but the associations between radiographic findings and clinical symptoms are weak to moderate and vary across studies. OA is, indeed, recognized to involve the whole joint, and modern imaging techniques such as ultrasound (US) and magnetic resonance imaging (MRI) could be valuable tools for better evaluation of hand OA. Standardized scoring methods have been proposed for both modalities. Several studies have examined the validity of US features in hand OA, whereas knowledge of the validity of MRI is more limited. However, both synovitis (detected by either US or MRI) and MRI-defined bone marrow lesions have been associated with pain, indicating that treatment of inflammation is important for pain management in hand OA. Both US and MRI have shown better sensitivity than CR in detection of erosions, and this may indicate that erosive hand OA may be more common than previously thought.
PMCID: PMC3334630  PMID: 22189142
15.  Why radiography should no longer be considered a surrogate outcome measure for longitudinal assessment of cartilage in knee osteoarthritis 
Imaging of cartilage has traditionally been achieved indirectly with conventional radiography. Loss of joint space width, or 'joint space narrowing', is considered a surrogate marker for cartilage thinning. However, radiography is severely limited by its inability to visualize cartilage, the difficulty of ascertaining the optimum and reproducible positioning of the joint in serial assessments, and the difficulty of grading joint space narrowing visually. With the availability of advanced magnetic resonance imaging (MRI) scanners, new pulse sequences, and imaging techniques, direct visualization of cartilage has become possible. MRI enables visualization not only of cartilage but also of other important features of osteoarthritis simultaneously. 'Pre-radiographic' cartilage changes depicted by MRI can be measured reliably by a semiquantitative or quantitative approach. MRI enables accurate measurement of longitudinal changes in quantitative cartilage morphology in knee osteoarthritis. Moreover, compositional MRI allows imaging of 'pre-morphologic' changes (that is, visualization of subtle intrasubstance matrix changes before any obvious morphologic alterations occur). Detection of joint space narrowing on radiography seems outdated now that it is possible to directly visualize morphologic and pre-morphologic changes of cartilage by using conventional as well as complex MRI techniques.
PMCID: PMC3334624  PMID: 22136179
16.  Multiplex, megaplex, index, and complex: the present and future of laboratory diagnostics in rheumatology 
In a recent issue of Arthritis Research & Therapy, Chandra and colleagues described the use of multiple multiplex immunoassays and complex computer algorithms to investigate the possibility of improved laboratory diagnosis and novel classification of rheumatoid arthritis on the basis of biomarkers. Such complex predictive tools in rheumatology can be guided by the experience of multiplex testing in oncology, which has demonstrated the importance of uniform specimen handling and prospectively collected specimen repositories. Although there are high expectations for these complex approaches, they require careful evaluation.
PMCID: PMC3334626  PMID: 22129036
17.  Imaging in gout - What can we learn from MRI, CT, DECT and US? 
There are many exciting new applications for advanced imaging in gout. These modalities employ multiplanar imaging and allow computerized three-dimensional rendering of bone and joints (including tophi) and have the advantage of electronic data storage for later retrieval. High-resolution computed tomography has been particularly helpful in exploring the pathology of gout by investigating the relationship between bone erosions and tophi. Magnetic resonance imaging and ultrasonography can image the inflammatory nature of gouty arthropathy, revealing synovial and soft tissue inflammation, and can provide information about the composition and vascularity of tophi. Dual-energy computerized tomography is a new modality that is able to identify tophi by their chemical composition and reveal even small occult tophaceous deposits. All modalities are being investigated for their potential roles in diagnosis and could have important clinical applications in the patient for whom aspiration of monosodium urate crystals from the joint is not possible. Imaging can also provide outcome measures, such as change in tophus volume, for monitoring the response to urate-lowering therapy and this is an important application in the clinical trial setting.
PMCID: PMC3334625  PMID: 22085684
18.  Evidence of a role for Th17 cells in the breach of immune tolerance in arthritis 
Th17 cells are thought to play a pathogenic role in various autoimmune diseases. Cytokines secreted by Th17 cells like IL-17, IL-17F and IL-22 have the capacity to mediate a massive inflammatory response. These proinflammatroy cytokines are likely to mediate the pathogenic potential of Th17 cells. Recent evidence suggests a role for Th17 cells in the breach of immune tolerance. This might shed some new light on the pathogenic role of Th17 cells in autoimmunity.
PMCID: PMC3308102  PMID: 22077983
19.  Declining needs for total joint replacements for rheumatoid arthritis 
This millennium brings new views to rheumatology. Total joint replacement surgery is needed less often as active treatment strategies combined with availability of new medications has led to more effective rheumatoid arthritis control. This was beautifully shown in a recent issue of Arthritis Research & Therapy by a Swedish study that uses data from national registers and compares incidence rates for total hip and knee arthroplasties before and after the establishment of biologic agents use for rheumatoid arthritis
PMCID: PMC3308092  PMID: 22040689
20.  Use of administrative claims data for comparative effectiveness research of rheumatoid arthritis treatments 
Observational studies, particularly those using large administrative claims databases, have become increasingly popular sources of comparative effectiveness or comparative safety research. Studies using claims data often face challenges and criticisms due to the lack of certain clinical information, such as lifestyle risk factors, disease severity, and questionable accuracy of disease diagnoses. A novel, claims-based algorithm to evaluate the clinical effectiveness of rheumatoid arthritis medications has been developed and its performance seems promising, although further validation is needed.
PMCID: PMC3308086  PMID: 21996148
21.  Fibroblast growth factor 2: good or bad guy in the joint? 
Fibroblast growth factor 2 (FGF2) is a highly abundant growth factor found within the pericellular matrix of articular chondrocytes, but studies investigating its role have been conflicting. The paper reported by Yan and colleagues in the previous issue of Arthritis Research & Therapy proposes that differences in responses to FGF2 are most likely due to changes in the balance between the two major articular cartilage FGF receptors, FGFR1 and FGFR3. They show that the catabolic and anti-anabolic effects of FGF2 are mediated primarily through FGFR1 whereas the beneficial effects are through FGFR3. This balance is dynamic and is altered in disease and following growth factor stimulation in vitro.
PMCID: PMC3308067  PMID: 21996043
22.  Bisphosphonates for osteoarthritis 
Synovitis and subchondral bone turnover are associated with pain in osteoarthritis. Bisphosphonates provide tools for investigating these pathogenic mechanisms and also may have therapeutic potential. Translating preclinical findings into new treatments for human osteoarthritis requires a critical appraisal and refinement of animal models, identification of those pathogenic mechanisms that are amenable to intervention, and pharmacological targeting of those mechanisms in the right people at the right time.
PMCID: PMC3308068  PMID: 21996085
23.  More than just B-cell inhibition 
Despite tremendous advances in the therapy of rheumatoid arthritis (RA), there remains interest in oral agents that may offer benefits that are similar to, or better than, those of biologic therapies. In their paper, Chang and colleagues demonstrate the effectiveness of a Bruton tyrosine kinase (Btk) inhibitor in two models of RA. Btk inhibition impacts several pathways affecting both B-cell and macrophage activation, making it a promising target in RA. However, other kinase inhibitors have failed to transition from animal models to human therapy, so it remains to be seen whether a Btk inhibitor will have a role in the RA treatment armamentarium.
PMCID: PMC3239370  PMID: 21878134
24.  Desperately looking for the right target in osteoarthritis: the anti-IL-1 strategy 
Blocking IL-1 in patients with knee osteoarthritis is an attractive strategy. Cohen and colleagues report a randomised, placebo-controlled, multiple-dose trial using a monoclonal antibody blocking IL-1 type 1 receptor. They failed to show any positive results in terms of evolution of pain for up to 12 weeks, in line with the former trials using intraarticular injections of IL-1 receptor antagonist. A trend was observed, however, in a subgroup of patients with high level of pain at baseline. Although these data may suggest cessation of IL-1 therapy in osteoarthritis, other methods such as limited intraarticular anti-IL-1 delivery should still be considered.
PMCID: PMC3239369  PMID: 21888686

Results 1-25 (334)