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

Johns Hopkins University School of Medicine

Livia Casciola-Rosen, PhD
Ami Shah, MD

Project Overview

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

This year, we teamed up with colleagues in Engineering and Oncology at Johns Hopkins and performed studies that that used autoantibodies as tools to investigate molecular events linking cancer and the development of autoimmunity in scleroderma. We showed that autoantibodies and scleroderma phenotype define subgroups of patients at higher or lower risk of getting cancer. These findings will ultimately facilitate development of personalized cancer screening guidelines. These studies were recently published in the Annals of Rheumatic Diseases. We are now extending these studies with SRF funding to investigate novel cancer detection strategies in patient subgroups that have a higher risk of cancer.

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.

Role of the Scleroderma Research Foundation

In addition to providing direct funding for this project, the SRF’s long-standing support of the Johns Hopkins Scleroderma Center laid the groundwork for this project. Over many years, the SRF has provided funding that established and maintains the Johns Hopkins Scleroderma Center, enabling the establishment of a large repository of biospecimens from well-characterized scleroderma patients. Our studies looking for new antibodies are intimately linked with access to this serum bank, and could not be performed without it. This past year, we were successful in getting an RO1 grant funded from the National Institutes of Health for studies that directly arise out of and extend the work that was initiated with SRF support. We are extremely grateful to the SRF for their role in enabling this.  

As researchers, we also look forward to the annual SRF Workshop, which provides a wonderful opportunity for interaction between funded and prospective researchers, and the Scientific Advisory Board. We always return from this meeting with renewed enthusiasm and commitment for continuing our studies that will further understanding of scleroderma, and improve treatment for patients.

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