Post Vaccination Transcriptomic Profiling in Sarcoidosis Yields Pathways Associated with Decreased Immune Response

ABSTRACT

Introduction/Background Sarcoidosis is a T cell mediated systemic disease of unknown etiology that results in granulomatous inflammation and multiorgan dysfunction. Individuals with sarcoidosis have been shown to be at increased risk for infection arguing the importance of vaccination as a primary prevention strategy. However, current knowledge as to how individuals with sarcoidosis respond to vaccination is limited. Furthermore, proteomic and transcriptomic profiling post vaccination will offer integrated insight into the immune mechanisms that drive sarcoidosis disease. Objective(s) The objective of this study is to determine the quantitative antibody response to COVID-19 vaccination to correlate to the unique proteomic and transcriptomic profiles underlying the immune response. Methods With local institutional review board approval, a prospective case control study was conducted to compare the proteomic and transcriptomic profiles of subjects with and without sarcoidosis before and after vaccination with the BNT162b2 mRNA vaccine. Recruited subjects included individuals -18 years who received two doses of the vaccine at the University of Illinois (UIC). Sixteen subjects with biopsy proven sarcoidosis were recruited, six of whom were not on any treatment while 10 were on immunosuppressive therapy, while 23 age-gender matched healthy controls were recruited. Blood was sampled prior to each vaccine dose as well as one and seven days after vaccination. Anti-spike protein IgG titers and serum cytokine profiles were quantified with ELISA while bulk RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs). Results Sarcoidosis subjects had significantly less antibody production after two doses of the BNT162b2 mRNA vaccine than controls (p-val 0.0040). A multivariate regression analysis indicated that a sarcoidosis diagnosis (p-val 0.026) was significantly and independently predictive with lower follow up antibody titers, which was more pronounced if subjects were on immunosuppressive therapy (p-val 0.00013). Differential gene expression will compare temporal individual variation after vaccination and identify group differences to identify transcriptomic pathways associated with the diminished antibody response. Weighted gene co-expression analysis will identify likely expressed genes to determine distinct profiles that may be predictive of sarcoidosis disease. Conclusion Subjects with sarcoidosis mount a decreased antibody response to the BNT162b2 mRNA COVID-19 vaccine supporting a dysregulated immune response inherent to sarcoidosis pathogenesis. Correlated transcriptomic and proteomic profiling offers a unique opportunity to comprehensively study the genes and pathways underlying the immune response to vaccination in sarcoidosis.