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Principal Investigator: DANA P ASCHERMAN
Organization: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
Fiscal Year: 2024
Award: $237,514
Funding agency: National Institute of Arthritis and Musculoskeletal and Skin Diseases
The current SARS-CoV-2 pandemic has had devastating consequences, with more than 110,000,000 cases and
2,400,000 deaths worldwide. Beyond the direct effects of SARS-CoV-2 infection, much of the morbidity and
mortality stems from dysregulated activation of the immune system that culminates in systemic manifestations
ranging from cytokine storm to autoimmunity. Recent work suggests that the basis for observed autoimmune
complications of SARS-CoV-2 infection resides in the high degree of sequence overlap between viral proteins
and native tissue antigens. Given this sequence overlap and the potential for molecular mimicry/induction of
autoimmunity in the setting of SARS-CoV-2 infection, there is concern that vaccines geared towards the
generation of protective immune responses against the SARS-CoV-2 spike protein may increase the risk of
autoreactivity—particularly in patients with pre-existing autoimmune disease and associated immune
dysregulation. Because patients with underlying autoimmune diseases such as idiopathic inflammatory
myopathy, systemic sclerosis, rheumatoid arthritis, and primary Sjogren’s syndrome were not included in the
original trials of vaccines targeting the SARS-CoV-2 spike protein, there is a clear unmet need to better
understand the consequences of SARS-CoV-2 vaccination in these patient populations—both in terms of vaccine
response as well as the potential for disease exacerbation/development of de novo autoimmune manifestations.
Coupled with our well-established, longitudinal rheumatic disease database/biorepository that includes an
integrated data management system (RDMS=Rheumatic Disease Data Management System), our experience
with the use of remote digital platforms and assessment of patient reported outcomes (PROs) makes us uniquely
positioned to conduct successful observational studies of vaccine-induced clinical/immunological responses. To
evaluate the relationship between changes in clinical disease activity and vaccine-induced autoreactivity, we
have 3 specific aims. In Specific Aim 1, we will use general as well as disease-specific PROs at defined time
points pre- and post-vaccination to assess changes in disease activity over a 12 month period—and compare
these changes to pre-vaccination fluctuations in disease activity over a parallel time frame. In Specific Aim 2,
we will apply novel, radiolabel-free methods of immunoprecipitation and Difference in Gel Electrophoresis to
assess corresponding serum samples collected at pre- and post-vaccination time points and define vaccine-
induced shifts in autoantibody profile as well as the development of anti-spike protein antibodies. In Specific
Aim 3, we will use different statistical models to evaluate the relationship between these antibody profiles and
changes in clinical disease activity/de novo autoimmune manifestations. Successful completion of these aims
will directly address the existing knowledge gap surrounding vaccine responses in understudied rheumatic
disease patient populations and establish a clinical cohort/biorepository that will serve as an unparalleled
resource for biomarker development as well as future research in vaccine-associated immune alterations.
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