Transcriptome Profiles of IgA Nephropathy after COVID-19 mRNA Vaccination

Background: The onset of IgA nephropathy has not been fully understood, however, tonsillitis is known to associate with gross hematuria and disease progression. In the previous several years, we have experienced COVID-19 vaccines which have triggered IgA nephropathy with gross hematuria. Methods: We assessed the clinical features of 13 patients with vaccine-associated IgA nephropathy. Then we measured RNA expressions of peripheral blood mononuclear cells in patients with tonsillitis-associated (n=3) and vaccine-associated IgA nephropathy (n=3). Differential expression analysis and enrichment analysis were performed. Results: Most of gross hematuria in vaccine-associated IgA nephropathy occurred within one day after vaccinations and all cases of hematuria appeared after the second and subsequent shot. RNA sequencing identified 76 differentially expressed genes (DEGs) between tonsillitis-associated and vaccine-associated IgA nephropathy, which were enriched in gene ontology terms “MHC protein complex” and “MHC class I protein complex”. DEGs upregulated in tonsillitis-associated IgA nephropathy were related to regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell. However, the upregulated gene set of vaccine-associated IgA nephropathy was related to positive regulation of T cell activation. Conclusion: The antigen presenting process could be different between tonsillitis-associated and vaccine-associated IgA nephropathy which may be crucial for their pathogenesis. Immune reaction of antigen presenting cells to extracellular vesicles containing mRNA vaccine could be a key to understand vaccine-associated IgA nephropathy.