mTOR activation triggers proinflammatory expansion of IL-4-producing and necrosis-prone double-negative T cells, precedes flares, and serves as target for treatment in patients with systemic lupus erythematosus

Abstract

The protracted diagnostic period and variable disease presentation not only complicate diagnosing SLE but also the epidemiologic study of it. Coupled with the remitting and relapsing nature of the disease and the challenges in managing it, clinical research in lupus requires careful attention to study design, control selection, temporality, and many often overlooked issues in the analysis phase. Between "big data" and the impressive advances in the basic sciences, it is tempting to either oversimplify methods to take advantage of "big data" or overcomplicate because the problem itself is complicated. As we revisit the building blocks of epidemiologic research, we will uncover opportunities to move epidemiology and clinical research forward in SLE. Why do we care about effect modification and what is it? Why can we not just adjust for everything that we want to? And perhaps, most importantly, going back to the very beginning and asking ourselves: does this matter? During this talk we will discuss issues relating to case identification methods, potential biases associated with control selection, and return to the basics of epidemiologic research. Although we shall discuss these issues in the context of environmental (nongenetic) factors, these concerns extend across the worlds of observational data analysis, can impact randomized trials, and are relevant for all types of exposures and outcomes. A2Is prevention of systemic lupus erythematosus a goal? Nancy J Olsen Background: Prevention of systemic lupus erythematosus (SLE) presents many challenges. By contrast, prevention of acquired immunodeficiency syndrome (AIDS) is relatively straightforward: an infective agent has been identified, risk behaviors are well-delineated, antiviral therapeutics are highly effective and neonates have been apparently cured. Lupus is a more complex disease, with a significant but incompletely defined genetic component, widely heterogeneous manifestations and major gaps in knowledge about pathogenesis. Methods: The characteristic features of SLE can be exploited in the quest for preventive strategies. One of these is the presence of a latent phase during which expressed autoantibodies are increasing in number and complexity prior to the onset of clinical symptoms. This offers a path to the development of screening blood tests that would be cost-effective and generally acceptable to subjects. ANA alone is clearly not sufficient to establish risk, as it is highly prevalent in the healthy population. Alternatively, a panel of autoantibodies, possibly combined with cytokines and gene expression levels, might be useful. The skewed demographics of SLE can also be exploited, including the higher prevalence in females, firstdegree relatives and individuals < 40 years old, permitting focus on those who are most likely to be at risk. Results: A composite index, with demographics and multiplex blood autoantibody profiles, has been proposed. This index showed statistically significant correlation with progression of disease in a small prospective ...