Patients with hypothermic sepsis have a unique gene expression profile compared to patients with fever and sepsis
The pathophysiology of hypothermia during sepsis is unclear. Using genomic profiling of blood leukocytes, we aimed to determine if hypothermia is associated with a different gene expression profile compared to fever during sepsis. Patients with sepsis and either hypothermia or fever within 24 hours...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Wiley
2022
|
| _version_ | 1826309000887533568 |
|---|---|
| author | Harmon, MBA Scicluna, BP Wiewel, MA Schultz, MJ Horn, J Cremer, OL Poll, T Wiersinga, WJ Juffermans, NP Mars Consortium |
| author_facet | Harmon, MBA Scicluna, BP Wiewel, MA Schultz, MJ Horn, J Cremer, OL Poll, T Wiersinga, WJ Juffermans, NP Mars Consortium |
| author_sort | Harmon, MBA |
| collection | OXFORD |
| description | The pathophysiology of hypothermia during sepsis is unclear. Using genomic profiling of blood leukocytes, we aimed to determine if hypothermia is associated with a different gene expression profile compared to fever during sepsis. Patients with sepsis and either hypothermia or fever within 24 hours after ICU admission were included in the study (n = 168). Hypothermia was defined as body temperature below 36 °C. Fever was defined as body temperature equal to or above 38.3°C. We compared blood gene expression (whole-genome transcriptome in leukocytes) in hypothermic septic compared to febrile septic patients in an unmatched analysis and matched for APACHE IV score and the presence of shock. In total, 67 septic patients were hypothermic and 101 patients were febrile. Hypothermia was associated with a distinct gene expression profile in both unmatched and matched analyses. There were significant differences related to the up- and downregulation of canonical signalling pathways. In the matched analysis, the top upregulated gene was cold-inducible mRNA binding protein (CIRBP) which plays a role in cold-induced suppression of cell proliferation. In addition, we found three signalling pathways significantly upregulated in hypothermic patients compared to febrile patients; tryptophan degradation X, phenylalanine degradation IV and putrescine degradation III. In conclusion, there are distinct signalling pathways and genes associated with hypothermia, including tryptophan degradation and CIRBP expression, providing a possible link to the modulation of body temperature and early immunosuppression. Future studies may focus on the canonical signalling pathways presented in this paper to further investigate spontaneous hypothermia in sepsis. |
| first_indexed | 2024-03-07T07:27:42Z |
| format | Journal article |
| id | oxford-uuid:a3c6c786-d989-496f-a176-807dab08d995 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:27:42Z |
| publishDate | 2022 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:a3c6c786-d989-496f-a176-807dab08d9952022-11-25T12:28:03ZPatients with hypothermic sepsis have a unique gene expression profile compared to patients with fever and sepsisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a3c6c786-d989-496f-a176-807dab08d995EnglishSymplectic ElementsWiley2022Harmon, MBAScicluna, BPWiewel, MASchultz, MJHorn, JCremer, OLPoll, TWiersinga, WJJuffermans, NPMars ConsortiumThe pathophysiology of hypothermia during sepsis is unclear. Using genomic profiling of blood leukocytes, we aimed to determine if hypothermia is associated with a different gene expression profile compared to fever during sepsis. Patients with sepsis and either hypothermia or fever within 24 hours after ICU admission were included in the study (n = 168). Hypothermia was defined as body temperature below 36 °C. Fever was defined as body temperature equal to or above 38.3°C. We compared blood gene expression (whole-genome transcriptome in leukocytes) in hypothermic septic compared to febrile septic patients in an unmatched analysis and matched for APACHE IV score and the presence of shock. In total, 67 septic patients were hypothermic and 101 patients were febrile. Hypothermia was associated with a distinct gene expression profile in both unmatched and matched analyses. There were significant differences related to the up- and downregulation of canonical signalling pathways. In the matched analysis, the top upregulated gene was cold-inducible mRNA binding protein (CIRBP) which plays a role in cold-induced suppression of cell proliferation. In addition, we found three signalling pathways significantly upregulated in hypothermic patients compared to febrile patients; tryptophan degradation X, phenylalanine degradation IV and putrescine degradation III. In conclusion, there are distinct signalling pathways and genes associated with hypothermia, including tryptophan degradation and CIRBP expression, providing a possible link to the modulation of body temperature and early immunosuppression. Future studies may focus on the canonical signalling pathways presented in this paper to further investigate spontaneous hypothermia in sepsis. |
| spellingShingle | Harmon, MBA Scicluna, BP Wiewel, MA Schultz, MJ Horn, J Cremer, OL Poll, T Wiersinga, WJ Juffermans, NP Mars Consortium Patients with hypothermic sepsis have a unique gene expression profile compared to patients with fever and sepsis |
| title | Patients with hypothermic sepsis have a unique gene expression profile compared to patients with fever and sepsis |
| title_full | Patients with hypothermic sepsis have a unique gene expression profile compared to patients with fever and sepsis |
| title_fullStr | Patients with hypothermic sepsis have a unique gene expression profile compared to patients with fever and sepsis |
| title_full_unstemmed | Patients with hypothermic sepsis have a unique gene expression profile compared to patients with fever and sepsis |
| title_short | Patients with hypothermic sepsis have a unique gene expression profile compared to patients with fever and sepsis |
| title_sort | patients with hypothermic sepsis have a unique gene expression profile compared to patients with fever and sepsis |
| work_keys_str_mv | AT harmonmba patientswithhypothermicsepsishaveauniquegeneexpressionprofilecomparedtopatientswithfeverandsepsis AT sciclunabp patientswithhypothermicsepsishaveauniquegeneexpressionprofilecomparedtopatientswithfeverandsepsis AT wiewelma patientswithhypothermicsepsishaveauniquegeneexpressionprofilecomparedtopatientswithfeverandsepsis AT schultzmj patientswithhypothermicsepsishaveauniquegeneexpressionprofilecomparedtopatientswithfeverandsepsis AT hornj patientswithhypothermicsepsishaveauniquegeneexpressionprofilecomparedtopatientswithfeverandsepsis AT cremerol patientswithhypothermicsepsishaveauniquegeneexpressionprofilecomparedtopatientswithfeverandsepsis AT pollt patientswithhypothermicsepsishaveauniquegeneexpressionprofilecomparedtopatientswithfeverandsepsis AT wiersingawj patientswithhypothermicsepsishaveauniquegeneexpressionprofilecomparedtopatientswithfeverandsepsis AT juffermansnp patientswithhypothermicsepsishaveauniquegeneexpressionprofilecomparedtopatientswithfeverandsepsis AT marsconsortium patientswithhypothermicsepsishaveauniquegeneexpressionprofilecomparedtopatientswithfeverandsepsis |