The role of genetics and antibodies in sepsis

Giamarellos‐Bourboulis, Evangelos J.; Opal, Steven M.

doi:10.21037/atm.2016.08.63

Cited by 27 publications

(30 citation statements)

References 65 publications

(67 reference statements)

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“…However, in our small group of non-survivors, the percentage of lymphocytes rather than impaired kinetics over time was impressive. Recent studies have shown that patients with ARDS may respond differently to various therapy regimens [29,30], but whether this variability in response is due to genetic alterations [31], immune evasion by bacteria [32], or different stages of sepsis is unknown. This study has some limitations.…”

Section: Discussionmentioning

confidence: 99%

Intravenous immunoglobulin fails to improve ARDS in patients undergoing ECMO therapy

Prohaska¹,

Schirner²,

Bashota³

et al. 2018

j intensive care

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BackgroundAcute respiratory distress syndrome (ARDS) is associated with high mortality rates. ARDS patients suffer from severe hypoxemia, and extracorporeal membrane oxygenation (ECMO) therapy may be necessary to ensure oxygenation. ARDS has various etiologies, including trauma, ischemia-reperfusion injury or infections of various origins, and the associated immunological responses may vary. To support the immunological response in this patient collective, we used intravenous IgM immunoglobulin therapy to enhance the likelihood of pulmonary recovery.MethodsARDS patients admitted to the intensive care unit (ICU) who were placed on ECMO and treated with (IVIG group; n = 29) or without (control group; n = 28) intravenous IgM-enriched immunoglobulins for 3 days in the initial stages of ARDS were analyzed retrospectively.ResultsThe baseline characteristics did not differ between the groups, although the IVIG group showed a significantly reduced oxygenation index compared to the control group. We found no differences in the length of ICU stay or ventilation parameters. We did not find a significant difference between the groups for the extent of inflammation or for overall survival.ConclusionWe conclude that administration of IgM-enriched immunoglobulins as an additional therapy did not have a beneficial effect in patients with severe ARDS requiring ECMO support.Trial registrationClinical Trials: NCT02961166; retrospectively registered.

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Section: Discussionmentioning

confidence: 99%

Intravenous immunoglobulin fails to improve ARDS in patients undergoing ECMO therapy

Prohaska¹,

Schirner²,

Bashota³

et al. 2018

j intensive care

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“…There is a growing body of literature discussing genetic determinants as a cause of increased susceptibility to infection and sepsis [2,8,15,18,23,24]. Single nucleotide polymorphisms (SNPs) have garnered much interest as a potential diagnostic and prognostic tool for septic patients.…”

Section: Genetic Susceptibilitymentioning

confidence: 99%

“…Single nucleotide polymorphisms (SNPs) have garnered much interest as a potential diagnostic and prognostic tool for septic patients. Many of the gene SNPs associated with an increased predisposition to sepsis are involved in vital cellular functions such as pathogen recognition, phagocytosis, and cytokine production [24,25]. Polymorphisms in the Toll-like Receptor (TLR) 1 gene, an important component of the innate immune response to pathogens, are associated with increased organ dysfunction and mortality in sepsis.…”

Section: Genetic Susceptibilitymentioning

confidence: 99%

“…Gene SNPs can also confer a decreased susceptibility and survival benefit against sepsis and its complications [24]. A recent study from Rautanen and colleagues found that common variants in the FER gene, a non-transmembrane receptor tyrosine kinase involved in cell-cell adhesion, was associated with a significant decrease in 28-day mortality from pneumonia-derived sepsis.…”

Section: Genetic Susceptibilitymentioning

confidence: 99%

“…This limits their generalizability to populations that are disproportionately affected by these conditions [23,29,30]. Currently no study has correlated genomic data with long-term outcomes beyond 90-day mortality [24,25,27,28,31].…”

Section: Genetic Susceptibilitymentioning

confidence: 99%

See 2 more Smart Citations

Factors Underlying Racial Disparities in Sepsis Management

DiMeglio

Dubensky

Schadt

et al. 2018

Preprint

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Sepsis, a syndrome characterized by systemic inflammation during infection, continues to be one of the most common causes of patient mortality in hospitals across the United States. While standardized treatment protocols have been implemented, wide variability in clinical outcomes persist across racial groups. Specifically, Black and Hispanic populations are frequently associated with higher rates of morbidity and mortality in sepsis compared to the Caucasian population. While this is often attributed to systemic bias against minority groups, a growing body of literature has found patient, community, and hospital-based factors to be driving racial differences. In this article, we provide a focused review on some of the factors driving racial disparities in sepsis. We also suggest potential interventions aimed at reducing health disparities in the prevention, early identification, and clinical management of sepsis.

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Mathematical modeling of septic shock: an innovative tool for assessing therapeutic hypotheses

et al. 2019

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Septic shock is provoked by hyper-activation of the pro-inflammatory response after infection and the patient requires anti-inflammatory treatment. However, the immune system develops a compensatory mechanism where the resulting feedback leads to an anti-inflammatory response after the initial state, which is referred to as immunodeficiency. Therefore, the initial therapeutic treatment with anti-inflammatory intervention has failed for almost 20 years and it has been changed in the last 10 years based on modulation of the inflammatory response. Using in silico methods, it is possible to develop a new approach based on physiopathology for treating septic shock. According to our new mathematical model, we can consider the dysfunctional immune system in a patient with septic shock and modify two parameters at different times to determine a possible treatment, and bearing out the single nucleoid polymorphism (SNP) may predominate the further deterioration of sepsis. The result represents the initial anti-inflammatory treatment with interleukin-10 activation and an increased risk of mortality over time for the septic shock patient, excluding the early stages. However, a hypothetical treatment based on interleukin-10 inhibition can change the patient's immune stage and provide a new therapy according to our results, and show that the frequency of pro-inflammatory related gene SNP can be the possibility of increase sepsis risk. In conclusion, our proposed in silico method can explore therapeutic strategies and predict their associated efficacy and important factors, with the ultimate objective of improving treatments to reduce mortality.

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The role of genetics and antibodies in sepsis

Cited by 27 publications

References 65 publications

Intravenous immunoglobulin fails to improve ARDS in patients undergoing ECMO therapy

Intravenous immunoglobulin fails to improve ARDS in patients undergoing ECMO therapy

Factors Underlying Racial Disparities in Sepsis Management

Mathematical modeling of septic shock: an innovative tool for assessing therapeutic hypotheses

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