Review Articles in 2009

Microparticles, which are membrane-bound vesicles that are released from cells during cell activation and apoptosis, are emerging as important mediators of intercellular communication in the context of rheumatic disease. Levels of microparticles are increased in the blood of patients with rheumatic diseases, suggesting a role for microparticles not only in disease pathogenesis, but also as potential biomarkers in these diseases.

Treatment of renal disease associated with systemic lupus erythematosus remains inadequate despite advances in our understanding of the disease pathogenesis. As discussed in this Review, clinical trials are underway for a number of therapeutic agents shown to be successful in murine lupus. In addition, insights gleaned from animal studies could lead to new strategies for the treatment of lupus nephritis in humans.

Evidence is mounting that biologic agents used to treat rheumatoid arthritis and other inflammatory rheumatic diseases exert substantial effects not only on underlying inflammation but also on the vasculature. This article reviews the available evidence on the effects of infliximab, adalimumab, etanercept and rituximab on atherosclerosis and cardiovascular disease risk.

Musculoskeletal ultrasonography is emerging as a potentially useful tool for the assessment and management of patients with rheumatoid arthritis. In this Review, Dr. Andrew Brown describes the diverse applications and advantages of this imaging modality in the diagnosis, treatment and monitoring of rheumatoid arthritis in the clinic.

Bone tissue engineering involves the development of viable bone substitutes that restore and maintain the function of bone tissue. In this article, the authors provide an overview of the rapidly progressing field of bone tissue engineering, describing the various approaches at the level of the scaffold, cells, and growth factors, and identifying the advantages and limitations of each approach.

The immune and skeletal systems share several molecules, including cells, cytokines, transcription factors, signaling molecules and membrane receptors. In rheumatoid arthritis, the synovium is a site of active interplay between immune cells and bone cells, in which, as outlined in this Review, osteoclasts are stimulated by cytokines and molecules, such as receptor activator of nuclear factor κB ligand, to mediate structural damage.

Monitoring disease activity and physical function is a fundamental aspect of spondyloarthritis management. Advances and recommendations in the field of spondyloarthritis monitoring, both in routine care and in the presence of a specific indication, are discussed in this Review.

Epidemiologic, genetic and immunophenotypic evidence suggests that oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis are distinct etiopathologic conditions with some overlapping pathogenic pathways. As discussed in this Review, further research is needed before we can generate a full molecular picture of these chronic childhood arthropathies.

Psoriatic arthritis follows a chronic, progressive course in most patients and joint damage can occur early in the disease. This article discusses advances in early diagnosis of this inflammatory musculoskeletal disorder, the various therapies that are available, as well as general guiding principles for treatment.

Current therapies for RA focus on inhibition of synovitis, but do not adequately repair the bone damage that results from the imbalance of the osteoblast–osteoclast axis. Targeting key molecules involved in osteoclastogenesis and osteoblastogenesis might reduce bone destruction and enhance repair of erosions in this disease.

Tumor necrosis factor (TNF) is expressed at high levels in synovial tissue from patients with RA. Through preclinical studies, animal model studies and human trials, this cytokine was the first to be fully validated as a therapeutic target for RA. Several approaches to blocking TNF have been developed, demonstrating considerable benefit in most of the patients treated.

Interleukin-17 has been implicated in the pathogenesis of inflammatory arthritis. Evidence from animal models and preliminary results from trials in human disease highlight the emergence of this proinflammatory cytokine as a target for RA therapy.

Regulatory T cells are critically involved in immune homeostasis. Several established and experimental treatments for RA might work via effects on regulatory T cells. This Review discusses the potential benefits and pitfalls of targeting these cells to control autoimmunity.

Dendritic cells have a crucial role in inducing immunity and mediating immune tolerance. Current biologic therapies for RA target some of the cytokine products of dendritic cells, whereas emerging therapies are aimed at exploiting their tolerogenic capacity.

Premature aging of the immune system, driven by defective DNA maintenance and repair, could be responsible for the pathogenesis of RA. The authors discuss the phenomenon of premature immunosenescence in RA, and suggest that 'resetting' the immune system could be a novel therapeutic concept.

G-CSF and GM-CSF are well-known regulators of hematopoiesis, but these cytokines also have proinflammatory activity and are expressed in the joints of patients with rheumatoid arthritis. Antagonism of G-CSF or GM-CSF might represent a novel, safe and effective way of treating this disease.

Monoclonal antibodies directed against CD20 have emerged as an effective therapy for RA. Using this approach to target CD19 could provide a greater breadth of B-cell depletion with additional therapeutic benefits.

The therapeutic options for patients with rheumatoid arthritis (RA) have changed dramatically over the past two decades, as discussed in this Review. The current landscape of RA therapy in terms of available therapeutics is described, and accepted principles of RA management and some important controversies in this field are outlined.

Advances in imaging technologies such as MRI and ultrasonography have improved the evaluation of tissue injury and repair, providing better diagnostics of cartilage lesions. Various surgical procedures and nonoperative treatments can be used to treat cartilage lesions. New developments in the field of tissue engineering have defined a 'second generation' of potential repair strategies for cartilage defects. Many combinations of scaffolding materials, cell sources and bioactive factors are being investigated for the engineering of a successful cartilage tissue replacement.

Much progress has been made in understanding the pathogenesis of early inflammatory arthritis and in diagnosing and treating this disease, mainly through detection of the presence of anti-citrullinated protein antibodies and early implementation of combination therapy. However, early inflammatory arthritis still presents a challenge to clinicians in terms of individual patient prognosis, an improvement in which might facilitate earlier and more personalized therapeutic intervention and achieve increased rates of remission.