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

Detalhes bibliográficos
Autor(a) principal: Souza, Bruna Maria Bereta de
Data de Publicação: 2022
Outros Autores: Silva, Marcos Vinícius da, Oliveira, Leonardo Rodrigues de, Rodrigues-Júnior, Virmondes, Vito, Fernanda Bernadelli de, Moraes-Souza, Hélio
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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spelling 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)
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instname_str Instituto Superior de Educação Vera Cruz (VeraCruz)
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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
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dc.identifier.doi.none.fl_str_mv 10.34117/bjdv8n12-026