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26.  Vaccination under TNF blockade - less effective, but worthwhile 
Only after biological response modifiers have become available have we begun to understand some of the complex functions of TNF in the human immune system. TNF is clearly essential for fighting intracellular pathogens, but probably not essential for fighting tumors. TNF influence on the humoral immune response, in contrast, has been more complicated to decipher, since TNF blockade is associated with both autoantibody formation and (somewhat) reduced responses to vaccination. Novel data now show that TNF is good for the humoral immune response. Vaccinations still work, however, and should be strongly recommended.
PMCID: PMC3446474  PMID: 22577892
27.  Implication of new atherosclerotic carotid plaques in the cardiovascular outcome of patients with rheumatoid arthritis 
Early detection of atherosclerosis is of major importance to reduce the increased incidence of cardiovascular (CV) complications observed in patients with rheumatoid arthritis (RA). Prospective studies have shown that an abnormally increased carotid intima-media thickness and the presence of plaques assessed by carotid ultrasound are good markers to predict the development of CV events in these patients. Age, classic CV risk factors, and corticosteroid use are also predictors of new plaque formation in patients with RA. Active treatment of the disease may decrease the inflammatory burden, leading to a reduction in the progression of subclinical atherosclerosis in these patients.
PMCID: PMC3446405  PMID: 22414597
28.  Plasma proteins take their toll on the joint in osteoarthritis 
In their recent study, Sohn and colleagues identify multiple plasma proteins in the synovial fluid of patients with osteoarthritis (OA) and demonstrate the capacity of several of the proteins to activate macrophages via the innate immune receptor Toll-like receptor-4 (TLR-4). The authors speculate that the plasma proteins transit into the synovial compartment at sites of tissue damage where the endothelial barrier may be compromised, thus bringing them into contact with the articular surface and cells within the synovium. These results demonstrate a novel mechanism by which synovial inflammation can be initiated in patients with OA and how this process may contribute to the pathogenesis of OA joint pathology.
PMCID: PMC3446406  PMID: 22385929
29.  Inhibiting citrullination in rheumatoid arthritis: taking fuel from the fire 
Citrullination is a post-translational modification catalysed by peptidylarginine deiminase and is a common feature of inflammation. The presence of anti-citrullinated protein/peptide antibodies (ACPA), however, is unique to rheumatoid arthritis. Several lines of evidence suggest that ACPA are important in the pathogenesis of rheumatoid arthritis. A popular hypothesis for this pathogenesis is a two-hit model. The first hit gives rise to ACPA, and the second hit, an unrelated episode of synovial inflammation accompanied by citrullination, is perpetuated by the pre-existing antibodies. This model suggests that reducing citrullination might ameliorate disease. Recent findings indicate that citrullination closely correlates with inflammation, and that glucocorticoids decrease peptidylarginine deiminase expression independent of their other anti-inflammatory effects.
PMCID: PMC3392831  PMID: 22380578
30.  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
33.  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
34.  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
36.  Vasculogenesis in rheumatoid arthritis 
Decreased number and impaired functions of endothelial progenitor cells (EPCs) leading to impaired vasculogenesis have been associated with rheumatoid arthritis (RA). Defective vasculogenesis has also been implicated in premature atherosclerosis in RA. Recently, early-outgrowth monocytic and late-outgrowth hemangioblastic EPC subsets have been characterized. Hemangioblastic EPCs may exert increased numbers in active RA and may play a role in vascular repair underlying RA.
PMCID: PMC2888181  PMID: 20346090
38.  Is interleukin-1 a good target for therapeutic intervention in intervertebral disc degeneration: lessons from the osteoarthritic experience 
IL-1 plays a key role in disc degeneration and could be a valid target for inhibiting this process. IL-1 receptor antagonist (IL-1ra) might be a good candidate to inhibit IL-1 activity. However, many questions need to be addressed before contemplating therapy in humans. IL-1 blockade is also a great challenge in osteoarthritis and results from animal models suggest that IL-1ra may have beneficial effects. The clinical benefit of a local injection of IL-1ra in knee osteoarthritis may be limited by the antagonist's short half-life. Further studies with longer-lasting antagonists are needed to explore this new therapeutic approach.
PMCID: PMC2246235  PMID: 18086327
42.  Goldilocks, vitamin D and sarcoidosis 
While low levels of vitamin D can increase the risk for osteoporosis, excessive amounts of vitamin D may also be problematic. Hypercalcemia and hypercalcuria due to increased vitamin D activity occur in a significant proportion of sarcoidosis patients. Saidenberg-Kermanac’h and colleagues compared vitamin D levels with bone fragility fractures in their sarcoidosis clinic. They found that a 25-(OH) vitamin D level between 10 and 20 ng/ml was associated with the lowest risk of bone fractures and paradoxically higher levels increased the risk of bone fractures. Using less vitamin D supplementation may simultaneously lower the risk for bone fracture and hypercalcemia in sarcoidosis.
PMCID: PMC4060200  PMID: 25166268
45.  Using Discrete Choice Experiment to elicit patient preferences for osteoporosis drug treatments: where to from here? 
Osteoporosis is a disease that increases skeletal fracture risk and places a significant health and economic burden on patients, families, and health systems. Many treatment options exist, but patient use is suboptimal, thus undermining the potential cost-effectiveness of treatments. In the previous issue of Arthritis Research & Therapy, Hiligsmann and colleagues expanded the findings of previous studies to report, from a sample of 257 patients with osteoporosis, the preference to trade off clinical outcomes for the amenity provided by convenient dosing regimens. This editorial critiques the strengths and limitations of the methods, discusses the potential utility of patient treatment preferences, and suggests avenues for further research.
PMCID: PMC4060568  PMID: 25167089
46.  Cathelicidin antimicrobial peptide as a serologic marker and potential pathogenic factor in antineutrophil cytoplasmic antibody-associated vasculitis 
Antineutrophil cytoplasmic antibodies are associated with pauci-immune small-vessel vasculitis and crescentic glomerulonephritis. Cathelicidin LL37 is the human member of a family of antimicrobial peptides that are released from activated neutrophils and monocytes at sites of acute inflammation. Zhang and colleagues evaluated serum levels of cathelicidin LL37 and interferon-alpha in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and glomerulonephritis. Increased levels of cathelicidin LL37 and interferon-alpha were associated with AAV patients, particularly those with glomerular crescent formation. Cathelicidin LL37 may also be involved in the pathogenesis of AAV and thus could be a target for novel therapy. Cathelicidin LL37 is a promising new biomarker for active AAV, including aggressive crescentic glomerulonephritis, and may prove to be both a prognostic marker and a guide for treatment.
PMCID: PMC3978818  PMID: 25164257
49.  What autoantibody tests should become widely available to help scleroderma diagnosis and management? 
Anti-Th/To autoantibodies have been recognized as serological markers of systemic sclerosis (SSc) for more than 20 years. However, validated immunoassay kits to test this specificity have not been commercially available. SSc autoantibodies are basically mutually exclusive and are associated with a certain subset of the disease and/or with organ involvement. Anti-Th/To are generally considered to be markers of the limited cutaneous type of SSc with the involvement of certain internal organs. The excellent correlation between anti-Rpp25 as detected by their novel chemiluminescent method and anti-Th/To as detected by immunoprecipitation suggest that the new assays may become widely available tests for clinicians in future and could help to clarify the clinical significance of anti-Th/To in SSc as well as other conditions over different races or countries.
PMCID: PMC3978467  PMID: 23856077
50.  Synovial fluid CD1c+ myeloid dendritic cells – the inflammatory picture emerges 
Dendritic cells (DCs) comprise a heterogeneous group of antigen-presenting cells with many specialized functions, including essential constitutive roles in priming immune and autoimmune responses and in the maintenance of peripheral self-tolerance. At the interface of the innate and adaptive immune systems, they contribute considerably to the production of inflammatory and anti-inflammatory mediators with diverse functions. Emerging evidence suggests that the wide involvement of DCs in immunity and tolerance reflects the function of specialized DC subsets.
PMCID: PMC3978489  PMID: 24365031

Results 26-50 (3996)