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The field of genomics is an exciting new field being applied in medicine. Its use in treating some cancers, sepsis and burn patients has been very promising. As knowledge of genomics and application of microarrays expands, researchers are developing more intelligent ways to provide individualized care for patients. The plan of this research study is to apply the use of genomics as a tool for transplant in several capacities.
This research study is designed to develop methods of isolating relevant cell types via microarray plates, then extracting mRNA samples of those cell types and capturing their genetic profile. This will be done with the blood of up to ten healthy donors. Once this ability has been demonstrated, the next step will be to use these testing in several capacities in transplant patients. The research study plan involves following the genetic profile of 26 kidney transplant patients. One group will be followed prospectively starting at baseline, and then at various set time points. A second group will be sampled with the occurrence of clinical events. These events include viral, bacterial, and fungal infection, WBC < 2.5 or biopsy proven rejection episodes or normal graft function. Thus, the intention of the study is to demonstrate how immunosuppression alters the expression of this genetic expression of these T cells. In doing so, the study will provide a better understanding of the specific and true immunosuppressed state for any given patient.
The two specific aims of the research study are as follows: 1) Proof of concept with two parts. Firstly, the study plan is to prove that T cells that are very commonly involved in the immune response: CD2, CD3, CD4, and CD8 populations can be captured. These cells will be captured, lysed and their mRNA genomics will be mapped. The second part of the proof of concept will involve exposing the CD2, CD3, CD4 and CD8 populations ex vivo to various serum concentrations of tacrolimus - the main cornerstone immunosuppressive medication in solid organ transplant. Exposure of the three cell types to the various tacrolimus concentrations will demonstrate that there is testing that can detect mRNA transcripts corresponding to under, optimal and over immunosuppressed states. The quantify IL2 production of the three cell types under the various immunosuppressive conditions will then be measured. With these 2 parts of the first specific aim of the study, a technique that can readily and easily isolate the cell populations of interest from the transplant patients and can capture how these cell populations respond to immunosuppression at various concentrations will have been demonstrated. 2) The second specific aim of the research study is running this genomic profiling on kidney transplant recipients. For this portion of the study, there will be two cohorts. A cohort identified as the "prospective" group and a cohort labeled as the "event" group. For the prospective cohort, blood will be obtained from the patients at specific time points. Specifically, blood samples will be obtained in the pre-transplant setting when the patients present to the hospital for their transplant, then at post-kidney transplant day 0, 1, 2, 3 and 7 (+/- 1 day) and at day 14, 21, and 28 (+/-3 days). Blood samples will be obtained again at months 2, 3, 6, 9, and 12 (+/- 1 week ). For the second group, blood samples will be obtained at the time of "events", such as rejection, infection, etc., and apply the same series of tests to their blood. For this group, blood draws will be done at time 0(+/-1 day), at then at one week (+/-2 days), and at one, two and three months (+/-1 week) post time 0. There will be five blood samples collected per patient. For all patients, there will be a comparison of the standard collected clinical information on the patient - graft function, rejection, infection, immunosuppression levels - to the results of our transcriptomics. The culmination of the project will involve revealing how genomics of the specific types of T cells can more precisely reflect a patient's true immunosuppressed state by corresponding to high, optimal and low immunosuppressive clinical phenotypes, and thus allow transplant clinicians to more intelligently and accurately administer immunosuppressive medications.
This study will involve obtaining blood samples on the kidney transplant patients at the time in which they would otherwise have blood collected for standard clinical care. Consent will be obtained for the testing on their blood, but the patients will not suffer any additional pain or inconvenience of the testing. In coordination with the equipment and supplies currently being used by the trauma and critical care department's research, the investigators will organize the collection and running of the labs in a time efficient and minimally expensive way
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy Controls | Participants in this group will have a one time blood sample taken. |
| |
| Kidney Transplant Group | Participants in this group have had a kidney transplant and blood samples will be obtained as described in study plan |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Blood Sample | Other | A one time blood sample will be provided. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Genomics of the T-cells will be compared to the immunosuppressed state of kidney transplant patient. | Standard collected clinical information of patients will identify over, optimal and under immunosuppressive states (IS) in kidney transplant (txp) recipients. In txp care, the definition of IS is defined by the clinical picture of the patient. Patients who have infections are over immunosuppressed, patients who have rejection are under immunosuppressed. Patients with neither and good graft function with normal Cr & good urine output have optimal IS. The investigators hope to identify a genomic pattern of the mRNA of T cells that correlates with the clinical picture of over, under or optimal IS in a kidney txp patient. Blood will be collected at the time of the events & genomics will be run on the T cell mRNA from that blood of each type of patient. The specific T cell used (CD3, CD4 or CD8) will be determined by the proof of concept portion of the study. The investigators will update this portion of the study as this information is obtained after the proof of concept is completed. | 12 months |
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Inclusion Criteria:
Healthy Controls
Kidney Transplant Group
Exclusion criteria:
Healthy Control
Kidney Transplant Group
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Healthy Controls and Kidney Transplant Patients
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| Name | Affiliation | Role |
|---|---|---|
| Ali Zarrinpar, MD, PhD | University of Florida | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Florida | Gainesville | Florida | 32610 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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400 microliters of blood
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| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |