Genetic Variation and Immune Responses After Injury

Study Description

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Brief Summary:

Our overall hypothesis is that genetic variations in innate immunity genes predispose patients to varying responses after injury by altering the systemic and local inflammatory responses. In addition, we hypothesize that these genetic differences are associated with different clinical outcomes

Condition or disease
Sepsis; Pneumonia; Trauma; Burn; Injury

Detailed Description:

The goal of this research proposal is to identify relationships that exist between specific genetic markers, immune responses to injury and infection (sepsis), and post injury clinical outcomes. Specifically, we will investigate the clinical impact of mutations involved in the innate immune response, which likely influence host response. To accomplish this goal we will collect and analyze data from patients with acute thermal injury, the most quantitative inflammatory stimulus experienced by humans. In addition, we propose to further characterize the immunologic response parameters to injury and infection, and their role in complicated sepsis. In this way, we will identify parameters associated with unfavorable clinical outcomes, and determine how these parameters differ among individuals with different genotypes. We propose to 1) evaluate associations between candidate SNPs within the NOD2/RIP2 signaling pathway and clinical outcome following burn injury, 2) evaluate the functional effects of alternate alleles at candidate SNPs; finally 3), we will use genetically engineered animal models to determine whether mutations in the NOD2 or RIP2 genes alter myocardial signal transduction mechanisms shown to play a role in myocardial inflammation/dysfunction after burn trauma. These approaches should allow us to evaluate more extensively clinically relevant interactions between specific genetic polymorphisms, the cellular expression of immune mediators, and burn-induced immune dysfunction. The proposed research should uncover genetic and/or acute immune-inflammatory parameters that identify patients who are at "high risk" and could as a result make possible the targeted design of pharmacologic intervention strategies that will inhibit the toxic effects of LPS and other bacterial pathogen components without paralyzing the host immunity of patients

Study Design

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Study Type :	Observational
Estimated Enrollment :	2000 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Genetics of Innate Immune Response After Burn Trauma
Study Start Date :	August 2003
Estimated Study Completion Date :	October 2011

Groups and Cohorts

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Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Biospecimen Retention:   Samples With DNA

Blood, Tissue, Fluids

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
Sampling Method:	Probability Sample

Study Population

Burn, Trauma, and Surgical Patients

Criteria

Inclusion Criteria: All burn,trauma, or acute surgery victims admitted to the surgical, burn or trauma units within 24 hours of injury will be considered for inclusion.

Exclusion Criteria:severe immunosuppression, DNR, severe trauma, terminal diseases.

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Fernando A Rivera-Chavez, MD	214-648-3534	fernando.rivera@utsouthwestern.edu

Locations

United States, Texas
UT Southwestern Medical Center at Dallas	Recruiting
Dallas, Texas, United States, 75390-9160
Principal Investigator: Fernando A Rivera, MD

Sponsors and Collaborators

National Institute of General Medical Sciences (NIGMS)

Investigators

Principal Investigator:	Fernando A Rivera-chavez, MD	Univ of Texas Southwestern Medical Center at Dallas

More Information

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Publications:

Rivera-Chavez FA, Peters-Hybki DL, Barber RC, Lindberg GM, Jialal I, Munford RS, O'Keefe GE. Innate immunity genes influence the severity of acute appendicitis. Ann Surg. 2004 Aug;240(2):269-77.

Barber RC, Aragaki CC, Rivera-Chavez FA, Purdue GF, Hunt JL, Horton JW. TLR4 and TNF-alpha polymorphisms are associated with an increased risk for severe sepsis following burn injury. J Med Genet. 2004 Nov;41(11):808-13.

Rivera-Chavez FA, Peters-Hybki DL, Barber RC, O'Keefe GE. Interleukin-6 promoter haplotypes and interleukin-6 cytokine responses. Shock. 2003 Sep;20(3):218-23.

Rivera-Chavez FA, Wheeler H, Lindberg G, Munford RS, O'Keefe GE. Regional and systemic cytokine responses to acute inflammation of the vermiform appendix. Ann Surg. 2003 Mar;237(3):408-16.

Responsible Party:	Perry Adams, UT Southwestern Medical Center
ClinicalTrials.gov Identifier:	NCT00294697 History of Changes
Other Study ID Numbers:	5K08GM071646-03 ( U.S. NIH Grant/Contract )
First Posted:	February 22, 2006
Last Update Posted:	August 24, 2010
Last Verified:	August 2010

Keywords provided by National Institute of General Medical Sciences (NIGMS):

polymorphisms; innate immune response; immunomonitoring; immuno paralysis

Additional relevant MeSH terms:

Pneumonia; Lung Diseases; Respiratory Tract Diseases; Respiratory Tract Infections