Indicators of Immune and Neurohumoral Profile in Women of Fertile Age with Functional Disorders of the Autonomic Nervous System Associated with Polymorphic Variants of the HTR2A (rs7997012) and TP53 (rs1042522) Genes

Dolgikh, O.V.; Зайцева, Н. В.; Nikonoshina, N. A.; Алексеев, В. Б.

doi:10.1007/s10517-022-05523-1

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“…Large part of the investigations addressed its role on cancer ( De Souza et al, 2021 ), but interesting correlations on metabolic pathways, immune cells, and immune response have been recently suggested in COVID-19 ( Milani et al, 2022 ). Our results are in line with the differentially expressed role of P72- and R72-allele on immune checkpoint inhibitors and on the association of the G-allele or GG-genotype with imbalanced immune regulation ( Dolgikh et al, 2022 ) and immune dysfunction, ascribing to TP53 gene a crucial role in the immune response. In general, R72 carrying population is more susceptible to viral infection because the pro-inflammatory immune response is not as strong as the P72 population ( Lodhi et al, 2021 ).…”

Section: Discussionsupporting

confidence: 88%

Host genetics impact on SARS-CoV-2 vaccine-induced immunoglobulin levels and dynamics: The role of TP53, ABO, APOE, ACE2, HLA-A, and CRP genes

et al. 2022

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Background: Development and worldwide availability of safe and effective vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to fight severe symptoms of coronavirus disease 2019 (COVID-19) and block the pandemic have been a great achievement and stimulated researchers on understanding the efficacy and duration of different vaccine types.Methods: We investigated the levels of anti-SARS-CoV-2 antibodies (IgG) and neutralizing antibodies (NAbs) in 195 healthy adult subjects belonging to the staff of the University-Hospital of Ferrara (Italy) starting from 15 days up to 190 days (about 6 months) after the second dose of the BNT162b2 (Pfizer–BioNTech) mRNA-based vaccine (n = 128) or ChAdOx1 (AstraZeneca) adenovirus-based vaccine (n = 67) using a combined approach of serological and genomics investigations.Results: A strong correlation between IgG and NAb levels was detected during the 190 days of follow-up (r2 = 0.807; p < 0.0001) and was confirmed during the first 90 days (T1) after vaccination (r2 = 0.789; p = 0.0001) and 91–190 days (T2) after vaccination (r2 = 0.764; p = 0.0001) for both vaccine types (r2 = 0.842; p = 0.0001 and r2 = 0.780; p = 0.0001 for mRNA- and adenovirus-based vaccine, respectively). In addition to age (p < 0.01), sex (p = 0.03), and type of vaccine (p < 0.0001), which partially accounted for the remarkable individual differences observed in the antibody levels and dynamics, interesting genetic determinants appeared as significant modifiers of both IgG and NAb responses among the selected genes investigated (TP53, rs1042522; APOE, rs7412/rs429358; ABO, rs657152; ACE2, rs2285666; HLA-A rs2571381/rs2499; CRP, rs2808635/rs876538; LZTFL1, rs35044562; OAS3, rs10735079; SLC6A20, rs11385942; CFH, rs1061170; and ACE1, ins/del, rs4646994). In detail, regression analysis and mean antibody level comparison yielded appreciable differences after genotype stratification (P1 and P2, respectively, for IgG and NAb distribution) in the whole cohort and/or in the mRNA-based vaccine in the following genes: TP53, rs1042522 (P1 = 0.03; P2 = 0.04); ABO, rs657152 (P1 = 0.01; P2 = 0.03); APOE, rs7412/rs429358 (P1 = 0.0018; P2 = 0.0002); ACE2, rs2285666 (P1 = 0.014; P2 = 0.009); HLA-A, rs2571381/rs2499 (P1 = 0.02; P2 = 0.03); and CRP, rs2808635/rs876538 (P1 = 0.01 and P2 = 0.09).Conclusion: High- or low-responsive subjects can be identified among healthy adult vaccinated subjects after targeted genetic screening. This suggests that favorable genetic backgrounds may support the progression of an effective vaccine-induced immune response, though no definite conclusions can be drawn on the real effectiveness ascribed to a specific vaccine or to the different extent of a genotype-driven humoral response. The interplay between data from the polygenic predictive markers and serological screening stratified by demogeographic information can help to recognize the individual humoral response, accounting for ethnic and geographical differences, in both COVID-19 and anti-SARS-CoV-2 vaccinations.

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