Understanding Autoantibody Responses During Infection, Inflammation, and Post-Viral Syndromes

Date of Award

Fall 2025

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Immunobiology

First Advisor

Ring, Aaron

Abstract

Autoantibodies are proteins produced by the humoral immune system that mediate a diverse array of effects on the host. Although the importance of autoantibodies has long been recognized due to their association with a number of disease states, the mechanisms and inflammatory states that lead to the generation of autoantibodies are varied and unclear, particularly in humans. In this dissertation, I use COVID19 as a lens to study autoantibodies, first by comparing autoantibody dynamics during acute SARS-CoV2 infection and SARS-CoV2 mRNA vaccination. Using REAP, a novel, high-throughput autoantibody profiling technique, to study over 6,000 autoantibody reactivities, I show that autoantibodies are markedly stable during SARS-CoV2 mRNA vaccination, while individuals with COVID19 frequently generate new autoantibodies, some of which are likely to be functional. Next, I use REAP to investigate the role of autoantibodies and anti-viral antibodies in the post-infection syndromes long COVID and ME/CFS. In both conditions, I show that there is a lack of a unique autoantibody signature that could distinguish patients from controls. Instead, I found that both conditions are marked by elevated reactivity to herpesvirus surface antigens, suggesting a possible role for these viruses in the pathophysiology of post-infection syndromes.

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