The Use of DNA Microarray as a Biomarker for Scleroderma: the Mycophenolate Mofetil Response Signature in Skin

Monique Hinchcliff, MD, MS
Northwestern University
Feinberg School of Medicine

New Project Summary:

Systemic sclerosis (SSc) is a clinically diverse autoimmune disease of unknown etiology with chronic course and significant mortality. Patients are classified into limited or diffuse cutaneous subsets based on the extent of skin involvement; however, the course of SSc varies widely. Some patients in either clinical subset have indolent disease while others experience rapid decline and death. Clinical (sex, tempo of skin and internal organ disease progression, race) and laboratory information (presence of autoantibodies, anemia, high brain natriuretic peptide) are currently used to predict which patients are at risk for developing severe disease, but no reliable biomarker has been identified to date. A novel pathomechanism-based classification method utilizing biopsy samples of affected skin developed by SRF-investigator Dr. Michael Whitfield and his collaborators separates patients into smaller intrinsic subsets based on their gene-expression signatures. Dr. Hinchcliff is collaborating with the Whitfield lab to determine whether patients in the different intrinsic subsets will have different patterns of skin and internal organ disease and they are performing cross-sectional analyses to determine the clinical phenotype associated with each of the intrinsic subsets. Future longitudinal studies will determine if intrinsic subset analyses can predict disease course.

Research Update:

Currently, 33 patients with scleroderma have been enrolled and have given serial skin biopsies for gene expression analysis. Ninety-seven percent of participants are female, and the mean age is 50 years old, with a range from 18 years old to 68 years old. Seventy-six percent are White, 12% are Black, 6% are Hispanic, 3% are Asian and 3% are American Indian and White. Sixty-seven percent of patients have diffuse cutaneous systemic sclerosis (dcSSc), 30% have limited cutaneous systemic sclerosis and 3% have diffuse morphea. Sixty-seven percent of patients report disease duration of less than two years (first non-Raynauds symptom less than two years from the time of biopsy).  For all participants, detailed clinical data including modified Rodnan skin score, echocardiogram, pulmonary function test, computed tomography of the chest, autoantibody and laboratory data (including CPK, creatinine and hemoglobin) are collected. Additionally, a battery of new and legacy patient-reported outcome instruments is administered on an annual basis. Cross-sectional analyses are being performed to determine whether clinical phenotypes associate with each of the intrinsic subsets identified by microarray.

What this project means for people with scleroderma:

There are no reliable biomarkers that can predict which patients will develop progressive skin and lung disease that warrants aggressive treatment and which patients have mild disease that is unlikely to progress. These studies will determine if identification of intrinsic subset in skin gives additional SSc prognostic information.

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