Chronic fatigue syndrome is a disabling condition for 2.5 million Americans associated with prolonged fatigue, post-exertional malaise, and sleep disturbances. The cause of CFS remains unknown, and there are currently no available diagnostic tests to confirm disease. However, a substantial number of immune features have been measured in CFS. Given this problem, the objective of this project is to identify a panel of distinct antibody epitopes that can be used to identify cases of CFS using a blood test. In Aim 1, we will apply serum epitope repertoire analysis to determine the antibody epitope repertoires within a cohort of 200 CFS patients and 175 controls. Antibody epitopes occurring in CFS sera, and not controls will be identified using bioinformatics methods. A panel of motifs will be downselected using machine learning to optimize sensitivity and specificity within the discovery set. The performance of the panel will be measured in an independent set of specimens to determine sensitivity and specificity, and identify potential CFS subgroups. We will determine whether individual markers, or sets of markers, correlate with various clinical features of CFS. Infections with a variety of pathogens have been associated with the development of fatigue lasting one year or longer, and post-infection fatigue patients typically meet clinical criteria for CFS. Given the potential for heterogeneous infectious etiology, we hypothesize that CFS patients may exhibit increased rates of seropositivity for a broad set of infectious agents associated with fatigue. Using serum epitope repertoire analysis, we will determine whether IgG seropositivity for 20 infections (as a group) differs between CFS patients and controls. The proposed project may identify antibody biomarkers suitable for development of diagnostic immunoassay for CFS, and may elucidate whether prior or ongoing infections are associated with CFS.
Public Health Relevance Statement: Chronic fatigue syndrome (CFS), also known as myalgic encephalitis (ME), is a disabling condition affecting an estimated 2.5 million people in the United States. The cause of CFS remains unknown, and there are no objective laboratory diagnostic tests to confirm disease. Consequently, diagnosis of CFS remains exceptionally difficult, requiring the exclusion of a wide variety fatiguing illnesses. This project aims to apply advanced molecular discovery tools and computation to identify patterns of circulating antibodies that can be used to diagnose and monitor CFS patients using a blood test. This project also holds the potential to associate prior infections with the development of CFS.
Project Terms: Academy; acute infection; Adrenergic Agents; Affect; American; Antibodies; Antigens; Arthralgia; Autoantibodies; base; Binding; biobank; Bioinformatics; Biological Markers; biomarker discovery; Blood Tests; candidate marker; Caregivers; CD8-Positive T-Lymphocytes; Cell physiology; Centers for Disease Control and Prevention (U.S.); Cerebrospinal Fluid; Cholinergic Receptors; Chronic Fatigue Syndrome; Clinical; cohort; Collection; Communicable Diseases; Cost of Illness; Coxiella; Data Analyses; Data Set; Development; Diagnosis; Diagnostic; diagnostic biomarker; Diagnostic tests; Disease; Encephalitis; Epitopes; Etiology; Exclusion; Exertion; Exhibits; Facilities and Administrative Costs; Fatigue; Feeling; Fever Chills; flu; Gene Expression; Health Personnel; Healthcare Systems; Human Herpesvirus 4; Immune; immune activation; Immunoassay; Immunoglobulin G; Impaired cognition; Impairment; Individual; Infection; Infectious Agent; Infectious Mononucleosis; Inflammatory; interest; Laboratories; Laboratory Research; Longitudinal prospective study; lymph nodes; Machine Learning; Malaise; Measurable; Measurement; Measures; Methods; Molecular; Monitor; Muscarinics; Myalgia; Natural Killer Cells; Nuclear Antigens; Organism; Pain; pathogen; pathogenic bacteria; pathogenic virus; Patients; Pattern; Performance; Phase; Proteins; Psyche structure; Reporting; Research; Sensitivity and Specificity; seropositive; Seroprevalences; Serum; Signal Transduction; sleep abnormalities; Sleep disturbances; Small Business Innovation Research Grant; Societies; Sore Throat; Specificity; Specimen; Subgroup; Symptoms; Testing; tool; trend; United States
