#2021 Effects of SARS-CoV2 mRNA vaccine on human kidney tubular epithelial cells

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Abstract Background and Aims Evidence suggests that the broad use of LNP-mRNA vaccines during COVID-19 pandemic might increase the incidence of kidney diseases, such as IgA nephropathy. However, the exact pathomechanism remains unclear. Therefore, we aimed to investigate how renal tubular epithelial cells interact with the monovalent Comirnaty vaccine, and whether spike protein (SP1) is expressed by treated cells. Method Human proximal tubular epithelial cells (HK2) were seeded on 6-well plates at a density of 100 000 cells/well and treated with Comirnaty at 1 µg/mL, 0.1 µg/mL and 0.01 µg/mL dose for 24 hours. Liposome treated cells served as controls. After RNA isolation, we used RT-qPCR to estimate the vaccine load by using primers specific for the BNT162b2 vaccine mRNA sequence and the expression of inflammatory and fibrosis-related genes. SP1 protein expression was depicted by immunocytochemistry. Data are presented as mean ± SD and were statistically evaluated with one-way ANOVA. Results HK2 cells treated at 1 µg/mL, 0.1 µg/mL and 0 µg/mL depicted 1348 ± 419-fold, 364 ± 25-fold or 19 ± 3-fold vaccine RNA load, respectively (P < 0.01). This was associated with dose-dependent C3 mRNA expression in HK2 cells (4.5 ± 2.6-fold, 1.6 ± 0.4-fold and 1.5 ± 0.3-fold, respectively, P < 0.05). MCP-1 mRNA expression showed similar vaccine dose-dependent pattern (4.7 ± 1.5-fold, 3.6 ± 1.1-fold and 1.6 ± 0.1-fold, respectively, P < 0.05). Along with the inflammatory response, we observed the induction of transcription factor EGR2 (3.2 ± 1.8-fold, 2.0 ± 0.5-fold and 1.6 ± 0.5-fold, respectively). Interestingly, ACTA2 mRNA expression was also induced by the vaccine at 1 µg/mL and 0.01 µg/mL doses (2.9 ± 0.9-fold and 2.0 ± 0.4-fold, respectively, P < 0.05) but not after 0.01 µg/mL. SP1 protein was visualized by immunocytochemistry in all vaccine treated cells. Conclusion Our data indicate that LNP-mRNA vaccines may enter kidney tubular cells and induce complex cellular responses even at lower doses. The changes in EGR2 activity and inflammatory gene expression could explain widely reported vaccine related long-term side effects.

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