Defining Novel Autoantibodies that are Probes of Cancer-Induced Autoimmunity and Risk in Scleroderma

Livia Casciola-Rosen, PhD

Ami Shah, MD

Johns Hopkins University School of Medicine

Project Summary:

Dr. Casciola-Rosen and Dr. Shah: Emerging findings indicate that distinct subgroups of scleroderma patients have a high risk of cancer at the time scleroderma develops. These subgroups are marked by the presence of specific autoantibodies. We are only beginning to understand what the important autoantibodies are in this regard, and how they are associated with cancer risk. Our project aims to discover new scleroderma autoantibodies and disease patterns that predict either an increased or decreased risk of cancer developing in scleroderma.

Research Update:

Last year, we established novel methods for detecting new autoantibodies. This important step was accomplished in collaboration with Drs. Zeger and Wu, both at Johns Hopkins (JH), using biostatistical methods to analyze data from the JH Scleroderma Center’s clinical database. With this new statistical tool, we can now identify distinctive autoantibody patterns from blood samples and use this to cluster scleroderma patients into subgroups based on their autoantibody pattern. Our initial studies strongly suggest that this new method will provide important insights into possible anti-cancer immune responses present in some of these subsets. This new method will be used to further define subsets of scleroderma patients who are either susceptible or resistant to the emergence of cancers. This is relevant both clinically and to our investigation of disease mechanisms, and will be the focus of our work in the coming year.

How this work will impact patients:

Our proposed studies are designed to discover novel autoantibodies in two very specific subsets of scleroderma patients: those in which cancer is detected close in time (within five years) to the diagnosis of scleroderma, and those in which cancer is never detected. Defining antibodies that are specifically associated with cancer detection close to the time of scleroderma onset will eventually enable clinicians to predict cancer risk when patients are first seen in a rheumatology clinic, and to guide cancer screening tests. New antibodies associated with cancer protection will give important information about the mechanism of disease and will help to design more effective treatments.

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