Genetic Sequence Variants in <i>TLR4</i>, <i>MBL</i> or <i>IL-1</i> Receptor Antagonist is not Associated to Increased Risk for Febrile Neutropenia in Children with ALL
Sequence variants in genes involved in the immune system have previously been linked to neutropenia as well as infections in cancer patients. Sequence variants in genes coding for <i>TLR4</i>, <i>MBL</i>, and <i>IL-1Ra</i> were investigated in relation to clinical...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Children |
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| Online Access: | https://www.mdpi.com/2227-9067/7/12/296 |
| _version_ | 1797544466122276864 |
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| author | Martina Wahlund Malin Lindqvist Appell Ida Hed Myrberg Anna Berggren Anna Nilsson |
| author_facet | Martina Wahlund Malin Lindqvist Appell Ida Hed Myrberg Anna Berggren Anna Nilsson |
| author_sort | Martina Wahlund |
| collection | DOAJ |
| description | Sequence variants in genes involved in the immune system have previously been linked to neutropenia as well as infections in cancer patients. Sequence variants in genes coding for <i>TLR4</i>, <i>MBL</i>, and <i>IL-1Ra</i> were investigated in relation to clinical utility of identifying severe episodes of febrile neutropenia (FN) in a cohort of children undergoing treatment for acute lymphoblastic leukemia. The study included 122 children, where data on FN and microbiological findings were retrospectively collected from medical records. Sequence variants in genes coding for <i>MBL</i>, <i>TLR4</i>, and <i>IL-1Ra</i> were identified by pyrosequencing, TaqMan SNP genotyping assay, and gel electrophoresis. A total of 380 episodes of FN were identified and in 139 episodes, there was a microbiological defined infection. Age and treatment intensity were all associated with the risk of developing FN. No sequence variant was associated to increased numbers of FN episodes. Two sequence variants in the <i>TLR4</i> gene increased the risk of viral infection, whilst sequence variants in the <i>IL-1Ra</i> gene were associated to a decreased risk of bacterial blood-stream infection (BSI). The investigated sequence variants did not associate with increased risk for FN or to severe infections, as to why the clinical utility as a risk-stratification tool is low. Most episodes of FN were classified as fever with unknown origin, emphasizing the need for improved microbial detection methods. |
| first_indexed | 2024-03-10T14:00:55Z |
| format | Article |
| id | doaj.art-460ea7f90fe9474abbfe79b3638aa233 |
| institution | Directory Open Access Journal |
| issn | 2227-9067 |
| language | English |
| last_indexed | 2024-03-10T14:00:55Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Children |
| spelling | doaj.art-460ea7f90fe9474abbfe79b3638aa2332023-11-21T01:07:35ZengMDPI AGChildren2227-90672020-12-0171229610.3390/children7120296Genetic Sequence Variants in <i>TLR4</i>, <i>MBL</i> or <i>IL-1</i> Receptor Antagonist is not Associated to Increased Risk for Febrile Neutropenia in Children with ALLMartina Wahlund0Malin Lindqvist Appell1Ida Hed Myrberg2Anna Berggren3Anna Nilsson4Department of Medicine Solna, Division of Infectious Diseases, Karolinska Institutet, 171 64 Stockholm, SwedenDepartment of Medical and Health Sciences, Division of Drug Research, Linkoping University, 581 83 Linkoping, SwedenChildhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, 171 65 Stockholm, SwedenDepartment of Medicine Solna, Division of Infectious Diseases, Karolinska Institutet, 171 64 Stockholm, SwedenChildhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, 171 65 Stockholm, SwedenSequence variants in genes involved in the immune system have previously been linked to neutropenia as well as infections in cancer patients. Sequence variants in genes coding for <i>TLR4</i>, <i>MBL</i>, and <i>IL-1Ra</i> were investigated in relation to clinical utility of identifying severe episodes of febrile neutropenia (FN) in a cohort of children undergoing treatment for acute lymphoblastic leukemia. The study included 122 children, where data on FN and microbiological findings were retrospectively collected from medical records. Sequence variants in genes coding for <i>MBL</i>, <i>TLR4</i>, and <i>IL-1Ra</i> were identified by pyrosequencing, TaqMan SNP genotyping assay, and gel electrophoresis. A total of 380 episodes of FN were identified and in 139 episodes, there was a microbiological defined infection. Age and treatment intensity were all associated with the risk of developing FN. No sequence variant was associated to increased numbers of FN episodes. Two sequence variants in the <i>TLR4</i> gene increased the risk of viral infection, whilst sequence variants in the <i>IL-1Ra</i> gene were associated to a decreased risk of bacterial blood-stream infection (BSI). The investigated sequence variants did not associate with increased risk for FN or to severe infections, as to why the clinical utility as a risk-stratification tool is low. Most episodes of FN were classified as fever with unknown origin, emphasizing the need for improved microbial detection methods.https://www.mdpi.com/2227-9067/7/12/296febrile neutropeniaacute lymphoblastic leukemia<i>TLR4</i><i>MBL</i><i>IL-1Ra</i> |
| spellingShingle | Martina Wahlund Malin Lindqvist Appell Ida Hed Myrberg Anna Berggren Anna Nilsson Genetic Sequence Variants in <i>TLR4</i>, <i>MBL</i> or <i>IL-1</i> Receptor Antagonist is not Associated to Increased Risk for Febrile Neutropenia in Children with ALL Children febrile neutropenia acute lymphoblastic leukemia <i>TLR4</i> <i>MBL</i> <i>IL-1Ra</i> |
| title | Genetic Sequence Variants in <i>TLR4</i>, <i>MBL</i> or <i>IL-1</i> Receptor Antagonist is not Associated to Increased Risk for Febrile Neutropenia in Children with ALL |
| title_full | Genetic Sequence Variants in <i>TLR4</i>, <i>MBL</i> or <i>IL-1</i> Receptor Antagonist is not Associated to Increased Risk for Febrile Neutropenia in Children with ALL |
| title_fullStr | Genetic Sequence Variants in <i>TLR4</i>, <i>MBL</i> or <i>IL-1</i> Receptor Antagonist is not Associated to Increased Risk for Febrile Neutropenia in Children with ALL |
| title_full_unstemmed | Genetic Sequence Variants in <i>TLR4</i>, <i>MBL</i> or <i>IL-1</i> Receptor Antagonist is not Associated to Increased Risk for Febrile Neutropenia in Children with ALL |
| title_short | Genetic Sequence Variants in <i>TLR4</i>, <i>MBL</i> or <i>IL-1</i> Receptor Antagonist is not Associated to Increased Risk for Febrile Neutropenia in Children with ALL |
| title_sort | genetic sequence variants in i tlr4 i i mbl i or i il 1 i receptor antagonist is not associated to increased risk for febrile neutropenia in children with all |
| topic | febrile neutropenia acute lymphoblastic leukemia <i>TLR4</i> <i>MBL</i> <i>IL-1Ra</i> |
| url | https://www.mdpi.com/2227-9067/7/12/296 |
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