Impaired NK cell cytotoxicity in multiple myeloma caused by the homozygous A91V polymorphism in the perforin gene: a case report: Citotoxicidade de células NK prejudicada no mieloma múltiplo causada pelo polimorfismo A91V em homozigose no gene da perforina: um relato de caso
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Revista Veras |
DOI: | 10.34117/bjdv8n12-026 |
Texto Completo: | https://ojs.brazilianjournals.com.br/ojs/index.php/BRJD/article/view/54977 |
Resumo: | We describe a 58-year-old man diagnosed with IgG/Kappa multiple myeloma (International Staging System III) treated for eight years with polychemotherapy (VAD schee) and autologous peripheral hematopoietic stem cell transplantation. The patient studied was homozygous C272T polymorphism (PRF1272T/T) by analysis of perforin gene by direct sequencing. This SNP is considered pathogenic and leads to the substitution of the amino acid alanine for valine in codon 91 of the perforin protein. The cytotoxic lymphocytes (CLs) of the patient and of the healthy wild homozygous individual were evaluated for their cytotoxic capacity. Our results show that PRF1272T/T effector cells had significantly reduced ability to induce specific lysis of K562 cells. The NK cells of the patient had three times less intracellular perforin than observed in the wild-type individual. The gene expression of PRF1 and FAS did not differ between the individuals, however the expression of GZMB was approximately 2.5 times higher in the patient. It was also observed that the T-BET expression was approximately 1.7-fold higher and IFN-γ expression was 4.5-fold higher in the PRF1272T/T patient. In conclusion, functional analysis of the CLs of the patient revealed a significant decrease in their cytolytic capacity as well as the amount of perforin present in NK cell granules. |
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Impaired NK cell cytotoxicity in multiple myeloma caused by the homozygous A91V polymorphism in the perforin gene: a case report: Citotoxicidade de células NK prejudicada no mieloma múltiplo causada pelo polimorfismo A91V em homozigose no gene da perforina: um relato de casoperforin, granzyme bmultiple myelomanatural killer cellcase reportWe describe a 58-year-old man diagnosed with IgG/Kappa multiple myeloma (International Staging System III) treated for eight years with polychemotherapy (VAD schee) and autologous peripheral hematopoietic stem cell transplantation. The patient studied was homozygous C272T polymorphism (PRF1272T/T) by analysis of perforin gene by direct sequencing. This SNP is considered pathogenic and leads to the substitution of the amino acid alanine for valine in codon 91 of the perforin protein. The cytotoxic lymphocytes (CLs) of the patient and of the healthy wild homozygous individual were evaluated for their cytotoxic capacity. Our results show that PRF1272T/T effector cells had significantly reduced ability to induce specific lysis of K562 cells. The NK cells of the patient had three times less intracellular perforin than observed in the wild-type individual. The gene expression of PRF1 and FAS did not differ between the individuals, however the expression of GZMB was approximately 2.5 times higher in the patient. It was also observed that the T-BET expression was approximately 1.7-fold higher and IFN-γ expression was 4.5-fold higher in the PRF1272T/T patient. In conclusion, functional analysis of the CLs of the patient revealed a significant decrease in their cytolytic capacity as well as the amount of perforin present in NK cell granules.Brazilian Journals Publicações de Periódicos e Editora Ltda.2022-12-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://ojs.brazilianjournals.com.br/ojs/index.php/BRJD/article/view/5497710.34117/bjdv8n12-026Brazilian Journal of Development; Vol. 8 No. 12 (2022); 77154-77163Brazilian Journal of Development; Vol. 8 Núm. 12 (2022); 77154-77163Brazilian Journal of Development; v. 8 n. 12 (2022); 77154-771632525-8761reponame:Revista Verasinstname:Instituto Superior de Educação Vera Cruz (VeraCruz)instacron:VERACRUZenghttps://ojs.brazilianjournals.com.br/ojs/index.php/BRJD/article/view/54977/40571Copyright (c) 2022 Bruna Maria Bereta de Souza, Marcos Vinícius da Silva, Leonardo Rodrigues de Oliveira, Virmondes Rodrigues-Júnior, Fernanda Bernadelli de Vito, Hélio Moraes-Souzainfo:eu-repo/semantics/openAccessSouza, Bruna Maria Bereta deSilva, Marcos Vinícius daOliveira, Leonardo Rodrigues deRodrigues-Júnior, VirmondesVito, Fernanda Bernadelli deMoraes-Souza, Hélio2022-12-28T18:57:44Zoai:ojs2.ojs.brazilianjournals.com.br:article/54977Revistahttp://site.veracruz.edu.br:8087/instituto/revistaveras/index.php/revistaveras/PRIhttp://site.veracruz.edu.br:8087/instituto/revistaveras/index.php/revistaveras/oai||revistaveras@veracruz.edu.br2236-57292236-5729opendoar:2024-10-15T16:25:35.966474Revista Veras - Instituto Superior de Educação Vera Cruz (VeraCruz)false |
dc.title.none.fl_str_mv |
Impaired NK cell cytotoxicity in multiple myeloma caused by the homozygous A91V polymorphism in the perforin gene: a case report: Citotoxicidade de células NK prejudicada no mieloma múltiplo causada pelo polimorfismo A91V em homozigose no gene da perforina: um relato de caso |
title |
Impaired NK cell cytotoxicity in multiple myeloma caused by the homozygous A91V polymorphism in the perforin gene: a case report: Citotoxicidade de células NK prejudicada no mieloma múltiplo causada pelo polimorfismo A91V em homozigose no gene da perforina: um relato de caso |
spellingShingle |
Impaired NK cell cytotoxicity in multiple myeloma caused by the homozygous A91V polymorphism in the perforin gene: a case report: Citotoxicidade de células NK prejudicada no mieloma múltiplo causada pelo polimorfismo A91V em homozigose no gene da perforina: um relato de caso Impaired NK cell cytotoxicity in multiple myeloma caused by the homozygous A91V polymorphism in the perforin gene: a case report: Citotoxicidade de células NK prejudicada no mieloma múltiplo causada pelo polimorfismo A91V em homozigose no gene da perforina: um relato de caso Souza, Bruna Maria Bereta de perforin, granzyme b multiple myeloma natural killer cell case report Souza, Bruna Maria Bereta de perforin, granzyme b multiple myeloma natural killer cell case report |
title_short |
Impaired NK cell cytotoxicity in multiple myeloma caused by the homozygous A91V polymorphism in the perforin gene: a case report: Citotoxicidade de células NK prejudicada no mieloma múltiplo causada pelo polimorfismo A91V em homozigose no gene da perforina: um relato de caso |
title_full |
Impaired NK cell cytotoxicity in multiple myeloma caused by the homozygous A91V polymorphism in the perforin gene: a case report: Citotoxicidade de células NK prejudicada no mieloma múltiplo causada pelo polimorfismo A91V em homozigose no gene da perforina: um relato de caso |
title_fullStr |
Impaired NK cell cytotoxicity in multiple myeloma caused by the homozygous A91V polymorphism in the perforin gene: a case report: Citotoxicidade de células NK prejudicada no mieloma múltiplo causada pelo polimorfismo A91V em homozigose no gene da perforina: um relato de caso Impaired NK cell cytotoxicity in multiple myeloma caused by the homozygous A91V polymorphism in the perforin gene: a case report: Citotoxicidade de células NK prejudicada no mieloma múltiplo causada pelo polimorfismo A91V em homozigose no gene da perforina: um relato de caso |
title_full_unstemmed |
Impaired NK cell cytotoxicity in multiple myeloma caused by the homozygous A91V polymorphism in the perforin gene: a case report: Citotoxicidade de células NK prejudicada no mieloma múltiplo causada pelo polimorfismo A91V em homozigose no gene da perforina: um relato de caso Impaired NK cell cytotoxicity in multiple myeloma caused by the homozygous A91V polymorphism in the perforin gene: a case report: Citotoxicidade de células NK prejudicada no mieloma múltiplo causada pelo polimorfismo A91V em homozigose no gene da perforina: um relato de caso |
title_sort |
Impaired NK cell cytotoxicity in multiple myeloma caused by the homozygous A91V polymorphism in the perforin gene: a case report: Citotoxicidade de células NK prejudicada no mieloma múltiplo causada pelo polimorfismo A91V em homozigose no gene da perforina: um relato de caso |
author |
Souza, Bruna Maria Bereta de |
author_facet |
Souza, Bruna Maria Bereta de Souza, Bruna Maria Bereta de Silva, Marcos Vinícius da Oliveira, Leonardo Rodrigues de Rodrigues-Júnior, Virmondes Vito, Fernanda Bernadelli de Moraes-Souza, Hélio Silva, Marcos Vinícius da Oliveira, Leonardo Rodrigues de Rodrigues-Júnior, Virmondes Vito, Fernanda Bernadelli de Moraes-Souza, Hélio |
author_role |
author |
author2 |
Silva, Marcos Vinícius da Oliveira, Leonardo Rodrigues de Rodrigues-Júnior, Virmondes Vito, Fernanda Bernadelli de Moraes-Souza, Hélio |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Souza, Bruna Maria Bereta de Silva, Marcos Vinícius da Oliveira, Leonardo Rodrigues de Rodrigues-Júnior, Virmondes Vito, Fernanda Bernadelli de Moraes-Souza, Hélio |
dc.subject.por.fl_str_mv |
perforin, granzyme b multiple myeloma natural killer cell case report |
topic |
perforin, granzyme b multiple myeloma natural killer cell case report |
description |
We describe a 58-year-old man diagnosed with IgG/Kappa multiple myeloma (International Staging System III) treated for eight years with polychemotherapy (VAD schee) and autologous peripheral hematopoietic stem cell transplantation. The patient studied was homozygous C272T polymorphism (PRF1272T/T) by analysis of perforin gene by direct sequencing. This SNP is considered pathogenic and leads to the substitution of the amino acid alanine for valine in codon 91 of the perforin protein. The cytotoxic lymphocytes (CLs) of the patient and of the healthy wild homozygous individual were evaluated for their cytotoxic capacity. Our results show that PRF1272T/T effector cells had significantly reduced ability to induce specific lysis of K562 cells. The NK cells of the patient had three times less intracellular perforin than observed in the wild-type individual. The gene expression of PRF1 and FAS did not differ between the individuals, however the expression of GZMB was approximately 2.5 times higher in the patient. It was also observed that the T-BET expression was approximately 1.7-fold higher and IFN-γ expression was 4.5-fold higher in the PRF1272T/T patient. In conclusion, functional analysis of the CLs of the patient revealed a significant decrease in their cytolytic capacity as well as the amount of perforin present in NK cell granules. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-12-02 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://ojs.brazilianjournals.com.br/ojs/index.php/BRJD/article/view/54977 10.34117/bjdv8n12-026 |
url |
https://ojs.brazilianjournals.com.br/ojs/index.php/BRJD/article/view/54977 |
identifier_str_mv |
10.34117/bjdv8n12-026 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
https://ojs.brazilianjournals.com.br/ojs/index.php/BRJD/article/view/54977/40571 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Brazilian Journals Publicações de Periódicos e Editora Ltda. |
publisher.none.fl_str_mv |
Brazilian Journals Publicações de Periódicos e Editora Ltda. |
dc.source.none.fl_str_mv |
Brazilian Journal of Development; Vol. 8 No. 12 (2022); 77154-77163 Brazilian Journal of Development; Vol. 8 Núm. 12 (2022); 77154-77163 Brazilian Journal of Development; v. 8 n. 12 (2022); 77154-77163 2525-8761 reponame:Revista Veras instname:Instituto Superior de Educação Vera Cruz (VeraCruz) instacron:VERACRUZ |
instname_str |
Instituto Superior de Educação Vera Cruz (VeraCruz) |
instacron_str |
VERACRUZ |
institution |
VERACRUZ |
reponame_str |
Revista Veras |
collection |
Revista Veras |
repository.name.fl_str_mv |
Revista Veras - Instituto Superior de Educação Vera Cruz (VeraCruz) |
repository.mail.fl_str_mv |
||revistaveras@veracruz.edu.br |
_version_ |
1822183704652414976 |
dc.identifier.doi.none.fl_str_mv |
10.34117/bjdv8n12-026 |