Observational studyThe journal of trauma and acute care surgery2015
An FcγRIIa polymorphism with decreased C-reactive protein binding is associated with sepsis and decreased monocyte HLA-DR expression in trauma patients.
Observational study in The journal of trauma and acute care surgery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- Human Fcγ-receptors selectively respond to C-reactive protein isoforms.Frontiers in immunology · 2025Article
- The Trajectory of Alterations in Immune-Cell Counts in Severe-Trauma Patients Is Related to the Later Occurrence of Sepsis and Mortality: Retrospective Study of 917 Cases.Frontiers in immunology · 2020Article
- Genetic Variation in Low-To-Medium-Affinity Fcγ Receptors: Functional Consequences, Disease Associations, and Opportunities for Personalized Medicine.Frontiers in immunology · 2019Review
- Pentraxins and Fc Receptor-Mediated Immune Responses.Frontiers in immunology · 2018Review
- The role of genetics and antibodies in sepsis.Annals of translational medicine · 2016Review
- Identification of Haplotype Tag Single-Nucleotide Polymorphisms within the PPAR Family Genes and Their Clinical Relevance in Patients with Major Trauma.International journal of environmental research and public health · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 3 countries.
Funding
Abstract
backgroundA dysregulated immune response leading to sepsis is the most frequent cause of late posttraumatic deaths. We have found a novel anti-inflammatory pathway that is initiated by the acute phase protein, C-reactive protein (CRP), interacting with Fcγ receptor (FcγR) on monocytes. This pathway is protective in animal models of endotoxin shock. We hypothesized that genetic polymorphisms in the FcγR might contribute to monocyte responses and susceptibility to infectious complications after severe trauma.
methodsWe conducted an observational study on a prospectively identified cohort of adult patients with convenience enrollment admitted after severe trauma. We enrolled 66 patients and collected blood samples at enrollment and again at 48 hours and 72 hours. Patients were followed through their hospital stay, and any septic events before 14 days were recorded. Cytokine and CRP levels were determined in the plasma from all three blood draws. In addition, DNA was extracted from blood and analyzed for the 131 H/R FcγRIIa polymorphism that strongly affects the binding of IgG and CRP to this receptor.
resultsElevated levels of interleukin 8 (IL-8), IL-6, IL-10, monocyte chemotactic protein 1, and CRP were associated with reduced time to posttraumatic sepsis in Cox regression analysis. Expression of monocyte human leukocyte antigen DR less than 45% on patient monocytes was also associated with sepsis (hazard ratio, 3.15; 95% confidence interval, 1.45-6.93). Genetic analysis found that individuals with the polymorphism of the FcγRIIa receptor that binds CRP poorly were also more likely to have decreased monocyte human leukocyte antigen DR and posttraumatic sepsis. In vitro studies showed that CRP could attenuate monocyte deactivation in volunteers with the polymorphism of the FcγRIIa receptor that binds CRP.
conclusionOur findings suggest that a common genetic variation in the FcγRIIa receptor may contribute to infectious susceptibility in trauma patients. In vitro experiments suggest that this association is related to the inability of CRP to bind to this FcγRIIa receptor variant. LEVEL OF EVIDENCE: Prognostic study, level III.
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