BackgroundThe referral of patients with positive anti-nuclear antibody (ANA) tests has been criticized as an inappropriate use of medical resources. The utility of a positive ANA test in a central triage (CT) system was studied by determining the autoantibody profiles and clinical diagnoses of patients referred to rheumatologists through a CT system because of a positive ANA test.MethodsPatients that met three criteria were included: (1) referred to Rheumatology CT over a three year interval; (2) reason for referral was a “positive ANA”; (3) were evaluated by a certified rheumatologist. The CT clinical database was used to obtain demographic and clinical information and a serological database was used to retrieve specific ANA and/or extractable nuclear antigen (ENA) test results. Clinical information was extracted from the consulting rheumatologist's report.Results15,357 patients were referred through the CT system; 643 (4.1%) of these because of a positive ANA and of these 263 (40.9%) were evaluated by a certified rheumatologist. In 63/263 (24%) of ANA positive patients, the specialist provided a diagnosis of an ANA associated rheumatic disease (AARD) while 69 (26.2%) had no evidence of any disease; 102 (38.8%) had other rheumatologic diagnoses and 29 (11%) had conditions that did not meet AARD classification criteria. Of ANA positive archived sera, 15.1% were anti-DFS70 positive and 91.2% of these did not have an AARD.ConclusionsThis is the first study to evaluate the serological and clinical features of patients referred through a CT system because of a positive ANA. The spectrum of autoantibody specificities was wide with anti-Ro52/TRIM21 being the most common autoantibody detected. Approximately 15% of referrals had only antibodies to DFS70, the vast majority of which did not have clinical evidence for an AARD. These findings provide insight into the utility of autoantibody testing in a CT system.

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 ...