Reviews & Analysis

Many forms of functional decline are preventable, treatable or manageable, but a screening tool that can identify frail or vulnerable patients is much needed. This Review describes the methods currently available for non-specialist evaluation of patients at risk of functional decline, including behavioral, interview and questionnaire assessments.

Neutrophils are powerful mediators of tissue inflammation, and the balance between neutrophil survival and clearance is crucial to the resolution of inflammation. The cytokine granulocyte colony-stimulating factor is an important regulator of neutrophil production and survival. This Review discusses the roles of neutrophils and granulocyte colony-stimulating factor in chronic inflammatory diseases.

The creation of specific immune tolerance would allow autoimmune disease to be reversed without the need for nonspecific and potentially harmful immunosuppressive therapy. Important progress in research into immune tolerance is summarized in this Review, and the potential use of this technique in immunotherapy of autoimmune disease is discussed.

Pattern recognition molecules belonging to the innate immune response participate in the clearance of apoptotic cells. Among these molecules are the collectins C1q and mannose-binding lectin, and the pentraxins C-reactive protein, serum amyloid P component, and pentraxin 3. This Review discusses the prevalence, actions and clinical significance of these molecules in autoimmune conditions.

New insights into the etiology of rheumatoid arthritis have suggested that humoral autoimmunity might have a substantive, possibly even causal role in the pathogenesis of disease. In this Viewpoint, Dr Holers will discuss the basis of this hypothesis, focusing on the role of anti-cyclic citrullinated peptide antibodies.

A variety of retinal signs can occur in patients who have systemic vasculitides. Although retinal signs are usually treated by treatment of the systemic disease, specific therapy is indicated occasionally to preserve vision. This Review describes the pathogenesis, clinical features and treatment of retinal manifestations of systemic vasculitides.

In this Review, Lars Klareskog and colleagues discuss the experimental approaches that are used to address the issue of gene–environment interactions in the etiology of RA, focusing on the roles of the HLA-DR shared-epitope genes, smoking and anticitrulline immunity in this process.

There is increasing interest in the role of transcription factors in the pathogenesis of inflammatory arthritis. Biologic and genetic studies are adding to current knowledge, and revealing potential targets for anti-inflammatory therapies that aim to modulate transcription factor activity.

Initially used in the treatment of mood disorders, this form of psychotherapy has been extended to other conditions such as chronic pain states. This Review evaluates the role of cognitive behavioral therapy, alone or in combination with other modalities, in the management of patients with fibromyalgia.

Gene therapy suffers the negative perception of being unsafe, expensive and ultimately inapplicable in clinical practice. In this Viewpoint, the authors discuss the benefits of gene therapy being used to treat rheumatic disease, and the requirements that have to be satisfied in order for this to become a clinical reality.

Tumor necrosis factor (TNF) inhibitors have proven highly effective in improving the signs and symptoms of rheumatoid arthritis, in inhibiting the progression of joint damage, and improving patients' quality of life. This Viewpoint will discuss the major concern relating to the actual use of TNF inhibitors in the clinic: their relatively high acquisition costs.

Progress in our understanding of fibromyalgia has identified aberrant central pain processing as a key abnormality in affected individuals. This Review describes a multimodal approach to treating this central pain syndrome, using neuroactive drugs that modulate sensory processing, and nonpharmacologic therapies such as exercise and cognitive behavioral therapy.

The pathogenesis of the spondyloarthropathies is thought to relate to interactions between genes, including HLA-B27, bacteria, and innate and acquired immune responses. This Review provides an insight into the validity of the genes–bacteria–immune response paradigm, and explores how interactions between these factors might result in disease.

To achieve goodin vivofunction, engineered cartilage needs to exhibit biological and physical properties similar to those of native articular cartilage. Adult multipotent stem cells are considered the cell type of choice for cartilage tissue engineering; this emerging technology shows high promise for producing transplantable cartilage constructs to improve the function of degenerated joints.

The introduction of tumor necrosis factor antagonist therapies has transformed expectations for the management of rheumatoid arthritis. Although all available agents have demonstrated comparable clinical efficacy, heterogeneity of response and treatment failure has been observed in up to 40% of patients. This Viewpoint will discuss the use of alternative TNF-blocking therapy in patients who have failed treatment.

Randomized, blinded, controlled experiments have often been considered the highest level of evidence in the methodological hierarchy. This Viewpoint discusses the strengths and limitations of both observational studies and randomized controlled trials, and the benefits that can be gained by researchers and clinicians through the appreciation of both methods.

Our comprehension of the role of the complement system in autoimmunity and tissue injury in systemic lupus erythematosus has progressed since mice lacking early components of the complement pathway were developed. Elucidation of these disease mechanisms might lead to the development of improved therapeutic approaches.