Hypothesis of IgAN caused by COVID-19 vaccination. The most common systemic symptoms in IgAN patients caused by COVID-19 vaccination were fever, fatigue and pain, and renal symptoms were GH, proteinuria and AKI. COVID-19 vaccination stimulates antigen-presenting cells (APCs), eliciting innate and subsequent adaptive immune responses. The first hypothesis for the development of IgAN in patients is the production of multiple antiglycan antibodies that cross-react with pre-existing galactose-deficient O-glycans (Gd-IgA1, A). The second hypothesis is an increase in pathogenic IgA production similar to influenza vaccine (B). The third hypothesis is that the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein (S) acts as a superantigen, causing cytokine storms (C). The data indicated that the COVID-19 mRNA vaccine was effective in inducing spike antigen-specific IgA and IgG production and, after the second vaccination, elicited strong CD4+ T-cell and CD8+ T-cell responses and a strong antibody response. The CD4+ T-cell response is mainly of helper T-cell type 1, producing IFN-c, TNF-α and IL-2. The main responses of CD8+ T cells are IFN-γ and TNF.