Opinion

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.

B-cell-depletion therapy emerged as a new therapeutic option for systemic lupus erythematosus (SLE) about a decade ago. Promising results from several open-label studies, with respect to efficacy and safety, were marred by the failure of two large, randomized controlled studies of rituximab to meet their endpoints. Rather than writing off B-cell depletion, might we eventually be able to accept it as a useful approach for treating SLE?

Vaccines are vital for protecting us against infectious diseases, but they have also been linked with the development of autoimmunity. In this article, the authors discuss the causal and temporal interactions between vaccines and autoimmune phenomena, and possible mechanisms by which different components of vaccines might induce autoimmune disease.

Clinical guidelines and recommendations, as well as clinicians and patients, consider non-pharmacological modalities to be the mainstay of treatment for osteoarthritis (OA). Despite this consensus in opinion, however, the evidence base for the non-pharmacological management of hand and hip OA continues to lag far behind that for knee OA, which suggests that more research is required to optimize the management of hand and hip OA.

Since the 1970s, rheumatologists have increasingly reported seeing patients with milder onset of rheumatoid arthritis and a less-severe disease course than in preceding decades. Are these improvements attributable to earlier diagnosis, better therapeutic options, or simply a milder natural disease course? Uhlig and Kvien review the evidence for the perceived decrease in disease severity and discuss the potential reasons for this phenomenon.

Owing to the critical role of tumor necrosis factor in host immunity, patients receiving tumor necrosis factor inhibitors for the treatment of autoimmune disorders are at significantly increased risk of infection from a variety of pathogens. The authors review the evidence and provide expert opinion on how best to prevent opportunistic infections in this setting.

Over the past 5 years, there has been considerable interest in the search for new treatments for systemic lupus erythematosus; disappointingly, negative results have now been presented from several large clinical trials. What can we learn from the experience so far to ensure that future opportunities for the development of an effective therapy for this disease are not missed?

Biologic agents are fast becoming a mainstay of treatment for rheumatoid arthritis. The risk of bacterial and opportunistic infections in patients treated with these agents remains unknown, however, in part because of difficulties related to interpretation of relevant trial data.