Opinion in 2010

Despite preclinical evidence of the safety and efficacy of gene therapy for arthritis, few clinical trials have been undertaken. What are the constraints on the development of this therapeutic strategy, and are these barriers likely to be overcome?

MRI has emerged as an important tool for the assessment of rheumatoid arthritis, and in research has had a clear impact on how the disease process is understood. In this Perspectives article, the authors consider the role of MRI in the evaluation of rheumatoid arthritis, including pathogenesis, diagnosis and outcomes of therapy, and examine the issues that surround the use of MRI in clinical and research settings.

In the second of two Perspectives articles regarding the use of MRI to detect inflammatory lesions in early preclinical axial spondyloarthritis, van der Heijde et al. defend the inclusion of MRI sacroiliitis in the 2009 ASAS classification criteria and acknowledge the importance of expert opinion in the diagnosis of this disease.

In the first of two Perspectives articles regarding the use of MRI to detect inflammatory lesions in early preclinical axial spondyloarthritis, De Rycke and colleagues question the diagnostic value of this technique, citing inconsistencies and selection bias in a number of validation studies.

Antibodies to citrullinated enolase define a subset of rheumatoid arthritis (RA) associated with smoking and DR4 alleles. In this Perspectives article, the authors review epidemiological and genetic links between periodontitis (a disease in whichPorphyromonas gingivalis is a major pathogen) and RA and propose that that the association might be causal, due to molecular mimicry between epitopes on host and P. gingivaliscitrullinated enolases driving the autoimmune response.

Pregnancy in women with systemic lupus erythematosus (SLE) can be associated with substantial morbidity and mortality for both the mother and the unborn fetus. Findings from several studies have indicated that CD4⁺CD25⁺regulatory T cells have an important role in supporting a healthy pregnancy. In this article, the authors provide an overview of how regulatory T cells function in both SLE and pregnancy, as well as providing an insight into how therapeutic agents that induce these cells could promote successful pregnancy in women with SLE.

The mechanical effect of excess weight is commonly thought to be the direct cause of osteoarthritis. In this Perspectives article, the author questions whether the evidence actually supports this prevalent view, and instead proposes that the increase in adipose tissue associated with obesity might drive the development of widespread osteoarthritis.

The role of the transcription factor NFκB in osteoclasts and bone degradation is well understood. In this Perspectives article, the authors discuss its newly described inhibitory function in osteoblasts and bone formation, and how therapies that target NFκB might be beneficial in osteoporosis and other inflammatory bone diseases.

After decades during which little has changed with respect to the therapeutic options available to clinicians treating patients with lupus nephritis, the use of targeted biologic agents is emerging as a possible treatment strategy. The authors discuss the potential of these agents, including both B-cell-directed and T-cell-directed therapies, and consider the specific circumstances in which they should be used, either alone or combined with conventional or other new therapies.

Patients with systemic sclerosis have a better prognosis now than they did 30 years ago, and the frequency of renal-crisis-related death has decreased markedly. As a result, there is an increasing burden of cardiovascular disease in these patients. In this article, the authors describe the techniques that can be used to assess vascular damage, and outline the requirements of future research in this area.

In the extracellular space, DNA and RNA can function as immunostimulatory molecules, inducing the production of type I interferon, an important mediator in the pathogenesis of systemic lupus erythematosus. Nucleic acid autoantigens can also be displayed in or on small membrane-bound vesicles, which might enable these autoantigen-containing microparticles to function as autoadjuvants that can affect the immune system and influence B-cell fate.

Major developments in our knowledge of the genetic basis of SLE in the past few years have opened many potential avenues of research. In this article, the authors question whether these advances have been sufficient to fulfill early predictions that genetics can be used to provide personalized healthcare.

Anti-C1q antibodies are present in approximately one-third of patients with systemic lupus erythematosus (SLE), and are strongly associated with the development of proliferative lupus nephritis. It seems likely that these antibodies develop through mechanisms shared by other SLE autoantibodies, but what do we know about their clinical significance and pathophysiological role?

If a patient with rheumatoid arthritis does not respond to treatment with a tumor necrosis factor (TNF) inhibitor, which biologic agent should be administered next: a second anti-TNF agent or an agent with a different mechanism of action? This article explores the issues and evidence surrounding the physician's dilemma.

Despite the high number of patients who present to their rheumatologist with pain, this symptom remains undertreated in the clinic. In this Perspectives, David Borenstein explores reasons for the undertreatment of pain in patients with rheumatic disease, and argues that the rheumatologist's role in this regard should be brought to the forefront.

Methotrexate is a proven and efficacious therapy for inflammatory diseases such as rheumatoid arthritis. The main mechanism of action of methotrexate as an anti-cancer drug, at high doses, involves folate antagonism, but what other mechanisms might be operative in the use of this drug at lower doses as an effective anti-inflammatory agent?

Autoantibodies—predominantly antinuclear antibodies—are strong predictors of disease outcome and the pattern of organ complications in patients with systemic sclerosis (SSc). In conjunction with improved methods to detect and evaluate autoantibodies, this strong association offers a real chance for risk stratification and disease assessment in patients with SSc.