Research paperComparison between multiplex assays for autoantibody detection in systemic lupus erythematosus
Introduction
Since the first recognition of autoantibodies in SLE, their measurement and cognate antigenic specificities has been a cornerstone in understanding pathogenesis, assisting in diagnosis and facilitating decisions on treatment. Autoantibodies serve as biomarkers of disease activity (e.g. increasing levels of anti-dsDNA antibodies and nephritis (Yung and Chan, 2008)), predicting disease onset (e.g. anti-Ro and anti-La (Arbuckle et al., 2003)), identifying disease subsets (e.g. anti-Ro antibodies and photosensitivity (Cozzani et al., 2008)) and determining prognosis (e.g. anti-Ro and anti-La antibodies and neonatal lupus syndrome (Buyon et al., 1993)). The variability between laboratory assays for the measurement of autoantibodies is also well recognized and is attributed to differences in antigen substrates and the rigor of test conditions resulting in the preferential detection of high or low affinity autoantibodies (Fritzler et al., 2003).
Advances in the technology of immunoassay platforms now permit the rapid and simultaneous detection of multiple autoantibodies. Such techniques include the use of addressable laser beads, microarrays, microfluidics and nanobarcode particles (Fritzler, 2006). Although these assays have been established and validated using appropriate methodology, there is an acknowledged requirement to conduct post-marketing assessment of new diagnostic platforms. The aim of the current study was to determine the level of agreement between 3 immunoassays that are based on multiple autoantibody measurement and their association with global SLE disease activity, active lupus nephritis and cumulative organ damage.
Section snippets
Patients
Consecutive patients enrolled between June 2000 and January 2007 into the Dalhousie University Lupus Clinic Registry at the Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada were studied. The Clinic receives referrals from primary care physicians, general internists, rheumatologists and other subspecialties such as nephrology, dermatology and hematology in a referral base of approximately one million people and is the only designated lupus clinic in the region. All
Patients and autoantibodies
The demographic and clinical manifestations of the 192 SLE patients enrolled in the study are summarized in Table 2. The population was predominantly female and Caucasian with mean disease duration of almost 9 years. The frequency of autoantibodies detected by the three immunoassays is summarized in Table 3. The overall frequency of a positive ANA was very similar (75–77%) but the frequency of specific autoantibodies was more variable. Furthermore, this variability was not due simply to an
Discussion
The detection and quantification of autoantibodies is central to the diagnosis of autoimmune diseases in general and of SLE in particular. In addition, their presence provides guidance on the selection of patients for and their response to specific therapies, an area of increasing importance due to the development of targeted “biological” therapies for human SLE (Furie et al., 2008, Cancro et al., 2009, Ramos-Casals et al., 2009, Tew et al., 2009). Recent technological advancements have
Acknowledgements
John G. Hanly is supported in part by an unrestricted operating grant from Bio-Rad Laboratories. Li Su and Vern Farewell are supported by the MRC(UK) grant U.1052.00.009. Marvin J Fritzler holds the Arthritis Society Research Chair.
We are grateful for the support of the attending staff rheumatologists (Dr. E. Sutton, Dr. V. Bakowsky, Dr. D. Mosher, Dr. S. Ahmad, Dr. S. Shatshat, Dr. T. Taylor and Dr. J. Wong, Dr. E. Shaw) at Dalhousie University and Queen Elizabeth II Health Sciences Centre for
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