ACE2 and TMPRSS2 Potential Involvement in Genetic Susceptibility to SARS-COV-2 in Cancer Patients

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. One open question is whether genetics could influence the severity of symptoms. Considering the limited data on cancer patients, we analyzed public data repositories limited to investigate angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) expressions and genetic variants to identify the basis of individual susceptibility to SARS-CoV-2. Gene expression and variant data were retrieved from Tissue Cancer Genome Atlas, Genotype-Tissue Expression, and gnomAD. Differences in gene expression were tested with Mann-Whitney U-test. Allele frequencies of germline variants were explored in different ethnicities, with a special focus on ACE2 variants located in the binding site to SARS-CoV-2 spike protein. The analysis of ACE2 and TMPRSS2 expressions in healthy tissues showed a higher expression in the age class 20 to 59 years (false discovery rate [FDR] < 0.0001) regardless of gender. ACE2 and TMPRSS2 were more expressed in tumors from males than females (both FDR < 0.0001) and, opposite to the regulation in tissues from healthy individuals, more expressed in elderly patients (FDR = 0.005; FDR < 0.0001, respectively). ACE2 and TMPRSS2 expressions were higher in cancers of elderly patients compared with healthy individuals (FDR < 0.0001). Variants were present at low frequency (range 0% to 3%) and among those with the highest frequency, the variant S19P belongs to the SARS-CoV-2 spike protein binding site and it was exclusively present in Africans with a frequency of 0.2%. The mechanisms of ACE2 and TMPRSS2 regulation could be targeted for preventive and therapeutic purposes in the whole population and especially in cancer patients. Further studies are needed to show a direct correlation of ACE2 and TMPRSS2 expressions in cancer patients and the incidence of COVID-19

人間の海洋移動にともなう分散がフィリピン列島における媒介蚊ネッタイシマ蚊の集団遺伝構造に影響

長崎大学学位論文 [学位記番号]博（医歯薬）甲第794号 [学位授与年月日]平成27年9月18

Cytokeratin 20-expressing M cells in tonsils take up particulate antigen. A site for the delivery of vaccines against oral pathogens?

Quantitative and qualitative control of oral bacterial flora is a major issue in oral pathology and in the prophylaxis against cavities. Recent findings suggest that it is possible to induce local immune responses delivering antigens on palatine tonsils. M cells play an important role in the start of the immune response. These cells are located in the epithelia overlaying mucosal lymphoid follicles and are responsible for the uptake of particulate antigens. The identification of reliable markers for M cell is therefore extremely important. Since it has been reported that tonsillar immunization leads to the secretion of high levels of specific salivary antibody, we undertook a study to identify a marker for tonsillar M cells in order to plan strategies of oral immunization against oral pathogens. We studied cytokeratin 20 expression in rabbit tonsils by immunofluorescence and confocal microscopy. Cytokeratin 20 immunoreactive cells were observed in all samples examined. These cells were identified as M cells as they co-expressed vimentin, a well-known marker of rabbit M cells, and they actively uptook particulate material. It is therefore possible to hypothesize the use of tonsil M cells as a possible site for antigen delivery of particle-based vaccines against oral pathogens