U01AI176310

Predictive Drivers of New Onset, Relapse, and Progression of Human Autoimmunity in Skin - Abstract

Autoimmune diseases affect up to 8% of the US population, and their prevalence is rising, setting the stage for an impending public health crisis that we do not yet understand and are not prepared to face. Many autoimmune diseases disproportionately affect women and those with skin of color, potentially worsening existing health disparities within our population. We must define the mechanisms that drive this growing risk for autoimmunity so that we can better manage, or even prevent, a scourge of severe morbidity and mortality.

Skin diseases are among the most prevalent autoimmune diseases and are simple to study due to the ability to diagnose and track the progression of disease through direct observation and sampling using minimally invasive tools. Thus, skin diseases provide unique insight into mechanisms of autoimmunity that are difficult to determine when studying other organs and tissues.

We will leverage a multidisciplinary team of investigators, cutting-edge tools designed for at-home, longitudinal tissue sampling, and an innovative strategy to discover how autoimmunity begins, relapses, and spreads in a large population of at-risk individuals. We and others have determined that unaffected, non-lesional skin from patients with autoimmunity exists in a disease-specific "preclinical" state, but whether this predisposes the patient to develop disease is an open question. We hypothesize that a molecular immune signature drives a preclinical state within the skin that predisposes to disease initiation and advancement of autoimmunity to other organs.

To test this, we will use two ideally suited models of autoimmunity. To predict development of autoimmunity de novo as well as disease relapse, we will take advantage of the unique properties of vitiligo: a strong genetic component, early age of onset (majority <30 years old), strong association with other autoimmune diseases, high prevalence (>1%), and rapid relapse after stopping therapy. We will longitudinally monitor 200 individuals with vitiligo for disease relapse and 800 of their relatives who are "at-risk" for developing new onset disease.

To predict the "progression" of autoimmunity to other organs, we will monitor a cohort of patients with cutaneous lupus erythematosus (CLE): up to 20% of patients who initially exhibit skin-limited lupus eventually develop systemic disease, with a median time to progression of two years. We will monitor 50 subjects with CLE to detect disease progression to internal organs.

We will use these innovative tools on a large scale through "population multiomics" to define immune drivers of autoimmunity in patients and their family members over time. To test our hypothesis, we will use computational integration of clinical, genetic, and molecular data points to define a "preclinical signature" of autoimmunity and use it to predict disease initiation and systemic progression. This approach will provide insight into autoimmunity that will help physicians better manage, or even prevent, devastating consequences of these diseases in the future.

University Of Massachusetts Medical School

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Worcester, Massachusetts 01655 United States

Single Zip Code

Immune Drivers of Autoimmune Disease (IDAD) (U01 Clinical Trial Not Allowed) (RFA-AI-22-012)

Amendment Since initial award the total obligations have increased 235% from $1,264,957 to $4,237,221.