Precision Diagnosis using Antibodies in Rheumatic Disease: Identification of Novel Autoantigen Specificities Expressed by Circulating Cells in Systemic Lupus Erythematosus (SLE)
Felipe Andrade, MD, PhD
Each rheumatic disease is composed of various subtypes – these subsets behave differently in terms of complications and responses to therapy, but are not easily distinguished using currently available probes. This project will identify markers in Lupus’ patient’s blood, which will allow categorization into subgroups. These markers may allow more precise diagnosis, monitoring and choice of therapy in those affected by Lupus.
Precise Quantitation of Pathogenic Pathways in Rheumatic Diseases: Interferon Activation in Systemic Sclerosis
Francesco Boin, MD and John Hall, PhD
Scleroderma is a chronic systemic autoimmune disease, that is characterized by fibrosis or hardening (sclero) of the skin (derma) and vascular alterations, causing dysfunction in the tissues. A group of molecular signals called cytokines play a role in causing this dysfunction, but the primary drivers remain unknown. This project is based on some recent discoveries that allow the effects of interferons, proteins made and released by host cells in response to the presence of pathogens, to be distinguished in patient tissue. Scleroderma patients have evidence of a signature of interferon in their tissue and blood, but the precise interferon responsible for this effect remains unknown. This project will precisely define the role of specific interferons in different scleroderma patients, and potentially provide a way to select novel therapies that neutralize specific interferons.
Disease Subsets are the Foundation for Precisely Defining Disease Mechanism: ACE and Scleroderma Renal Crisis
Livia Casciola-Rosen, PhD
One of the devastating consequences of scleroderma is renal crisis, where patients develop severe hypertension and renal failure. An enzyme called ACE pays an important role in this process, and ACE inhibitors can be lifesaving. The source of ACE and the reasons for its high level expression remain unknown. This project will begin to identify the cells that express ACE in scleroderma renal crisis, findings that have implications for understanding disease mechanisms and future therapies.
Sampling Tiny Amounts of the Target Tissue in Individual Patients: Defining the Role of Autoimmunity in Causing Thyroiditis in Women Initiating Interferon-alpha Therapy for Hepatitis C
Jennifer Mammen, MD
Different patients are unique in their genetic make-up as are the pathways that predominate in amplifying tissue damage. Recent technological advances have revolutionized the ability to study multiple pathways simultaneously in very tiny amounts of tissue. In this project, the investigators will sample tiny amounts of tissue from patients upon initiation of therapy, and define ways to precisely quantify the activity of distinct molecular pathways in those “micro-biopsies”.