Genetic Variation and Immune Responses After Injury

NCT ID: NCT00294697

Last Updated: 2010-08-24

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 2000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2003-08-31
• Study Completion Date: 2011-10-31

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

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

Conditions

Sepsis; Pneumonia; Trauma; Burn; Injury

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Exclusion Criteria

-

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of General Medical Sciences (NIGMS)

NIH

Sponsor Role: lead

Responsible Party

UT Southwestern Medical Center

Principal Investigators

Fernando A Rivera-chavez, MD

Role: PRINCIPAL_INVESTIGATOR

Univ of Texas Southwestern Medical Center at Dallas

Locations

UT Southwestern Medical Center at Dallas

Dallas, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Fernando A Rivera-Chavez, MD

Role: CONTACT

fernando.rivera@utsouthwestern.edu

214-648-3534

References

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. doi: 10.1097/01.sla.0000133184.10676.26.

Reference Type: BACKGROUND

PMID: 15273551 (View on PubMed)

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. doi: 10.1136/jmg.2004.021600.

Reference Type: BACKGROUND

PMID: 15520404 (View on PubMed)

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. doi: 10.1097/01.shk.0000079425.52617.db.

Reference Type: BACKGROUND

PMID: 12923492 (View on PubMed)

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. doi: 10.1097/01.SLA.0000055274.56407.71.

Reference Type: BACKGROUND

PMID: 12616126 (View on PubMed)

Other Identifiers

5K08GM071646-03

Identifier Type: NIH

Identifier Source: org_study_id

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