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The past, present & future of ANA testing: history and challenges of ANA

Part 1 of 2
Published on June 30, 2020   26 min

Other Talks in the Series: Periodic Reports: Advances in Clinical Interventions and Research Platforms

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0:00
Hello, I'm Dr. Marvin Fritzler. I'm a professor of Medicine at the Cumming School of Medicine at the University of Calgary in Calgary, Alberta, Canada. I want to go over with you the past history, what's happening today, and the future of antinuclear antibody testing. I intend to take both a clinical and a research perspective.
0:23
In the first part of my presentation, I want to speak to a history of ANA and autoantibody testing. Talk about how there's been a tremendous increase or explosion in autoantibodies described in diseases like lupus. Talk about where are we now in terms of challenges of ANA and autoantibody testing, and how it can be applied in the clinical setting with a specific focus on ANA immunofluorescence patterns as they're being described today. In the second part, I want to talk about the changing bandwidth of ANA and autoantibody testing. Address the question, is the ANA indirect immunofluorescence assay the gold standard for ANA testing? Talk briefly about that seronegative gap, or ANA-negative lupus and related diseases. Then finish our discussion on where are we going with ANA and autoantibody testing in the future, looking at converging mega-trends, precision health, and lupus diagnostics. In that setting, looking at an explosion of not only biomarkers, but technology where we're moving to solid phase multi-analyte arrays with algorithmic analysis that is grounded in artificial intelligence, and machine learning.
1:38
First, a brief history of anti-nuclear antibody testing. In most minds we trace the history of anti-nuclear antibody testing to the serendipitous finding of Hargraves and his colleagues at the Mayo Clinic when they discovered the LE cell and published it in 1948. Shortly after, indirect immunofluorescence was used as a method to detect autoantibodies to cell tissues, using cryopreserved mouse and rat organ sections. That was followed in the 1960s by the development of immunodiffusion, hemagglutination, and complement fixation as technologies to measure anti-nuclear antibodies in a more quantitative and semi-quantitative way. That was followed in the 1970s by counter-immunoelectrophoresis, western blot and enzyme-linked immunosorbent assay or ELISA. By the mid 1970s, falling on the golden era of molecular biology was when autoantibodies and their description exploded in the literature. This is largely attributed to the use of new anti-nuclear antibody substrates such as the HEp-2 substrate, which is still used today. From the 1980s to the present, we use newer technologies of antigen arrays on planar surfaces, addressable laser bead immunoassays and today other related multi-analyte arrays.

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The past, present & future of ANA testing: history and challenges of ANA

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