Immune System Responses Related to Environmental Uranium Exposure

1
Immune System Responses Related to Environmental
Uranium Exposure DiNEH Project Results

• E. Erdei J. Lewis
• University of New Mexico, Health Sciences Center,
  
• College of Pharmacy, Community Environmental
  Health Program
• Navajo Nation Human Research Review Board
  Conference
• Window Rock, AZ
• November 16, 2011

2
(No Transcript)
3
Environmental Legacy Exposures Increase the
Likelihood of Several Diseases Autoimmune Disease

• Figures below show similar increases in risks
  for autoimmune disease (self-reported) based on
  an increase from 1 to 2 activities

4
DiNEH Survey Responses
5
Goal of this portion of the study

• Direct response to community members requests
  for research on immune system function during the
  capacity building and environmental risk
  evaluation work
• Address possible pathways within the human body
  in association with environmental uranium and
  other heavy metal exposures
• Find early indicators of
• health effects

6
DiNEH biological sample collection

• DiNEH project participants from 20 chapters
• Samples collected from 267 individuals
• A subset has been analyzed for immune biomarkers
  (N65)
• Early markers, showing alterations
• in immune cell distribution and activity

7
Flow cytometry measurements

• Lymphocyte subpopulations from whole blood
  samples.
• Becton Dickinson Simultest IMK Plus lymphocyte
  kit was used.
• 6 cell populations were measured
• T cells (CD3), T helpers (CD4), T suppressors
  (CD8)
• B cells (CD19)
• HLA-DR cell activation in T cells and
• B cells and other cell types NK cells
  (CD3-/CD16/CD56).

8
UNM HSC Core Facility

• Director Dr. Bruce Edwards
• Flow cytometry machine
• FACScan 2 lasers, 2-color
• simultaneous detection of lymphocytes
• Membrane markers, CD coding

9
Flow cytometry results I.
10
Flow cytometry results II.

• Increased percentage of activated T cells
• Decreased percentage of activated B cells
• Decoupling of T cell and B cell activities
  suggest altered immune response among this subset
  of participants
• Can lead to lower production of protective
  antibodies
• Preliminary interpretation of data more complex
  modeling incorporating other variables pending

11
Serum cytokines

• Cytokines are small molecular weight proteins
  produced by immune cells and other cells through
  the human body
• Their role is to promote communication,
  activation processes in the immune system
• Cytokine productions show immune status and
  disease developmental pathways

12
Serum cytokine measurements

• Applied xMAP multiplexing technology
• UNM HSC Core Facility- Luminex 100 detection
  (96-well format)
• Detection of 10 human serum cytokines (IL-1ß,
  IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, INF-?,
  TNF-a, and GM-CSF) high sensitivity assay
• Uses only 50 µl of serum sample/ participant

13
Serum cytokine concentrations related to
environmental uranium waste exposures
14
Serum cytokine concentrations (pg/ml) related to
environmental uranium waste exposures (N47)

• Percent of variance by exposure for IL-4 and
  IL-1ß suggests a potential inflammatory process

15
Conclusions

• Based on our preliminary analysis
• DiNEH participants with increased exposure to
  uranium waste had increased number of activated T
  cells and decreased activity of B cells and other
  antigen-producing cells
• If consistent w/ other modeling results (e.g.
  water source) indication of the decoupling of
  the immune response
• Alterations in cytokine production indicative of
  the presence of an inflammatory response

16
Future directions

• These results are based on our preliminary
  analyses work in progress
• To continue to complete immune assays for entire
  sample set
• Further modeling works will allow us more
  detailed evaluation of suggestive inflammatory
  response
• In connection with other pathway analyses
  cardiovascular process

17
DiNEH Acknowledgements

• NIEHS, EPA and UNM for financial support
• Community Advisory Board
• Ed Carlisle, Jay DeGroat, Herbert Enrico, Thomas
  Manning,Sr., Lynnea Smith, Jean Whitehorse,
• UNM-HSC Community Environmental Health Program
  Clinical and Translational Science Center
• Johnnye L. Lewis, PhD Miranda Cajero, BCH
  Matthew Campen, PhD Jeremy DeGroat Mallery
  Downs, RN Eszter Erdei, PhD Molly Harmon
  Gabriel Huerta, PhD Curtis Miller Bernadette
  Pacheco Glenn Stark Mary Woodruff research
  nursing support
• Crownpoint Service Unit, I H S
• Virgil Davis
• Navajo Area IHS
• Lisa Allee, CNM John Hubbard Ryan Johnson, MD
  Doug Peter, MD
• UT-Houston Nephrology
• Donald Molony, MD
• Southwest Research Information Center
• Chris Shuey, MPH, Sarah Henio-Adeky, Teddy Nez,
  Sandy Ramone

• Students
• Jamie deLemos, PhD Tufts Univ.
• Christine George Stanford Univ.
• Tommy Rock, MA, UNM Health Policy Student
• Christine Samuel-Nakamura, PhD Candidate, UCLA
• Dartmouth
• Ben Bostick, PhD
• University of Arizona Cancer Center Northern
  Arizona University, NACRP
• Jani Ingram, PhD, Margaret Briehl, PhD
• USEPA Region IX
• Harry Allen, Rich Bauer, Clancy Tenley
• State of New Mexico Diagnostic Laboratory
• Navajo Nation EPA Air Quality Division, Public
  Water Supply Supervision Program, Superfund
  Program
• Navajo Nation Division of Health
• Former Contributors
• Bess Seschillie, Bernice Norton, Jerry Elwood,
  Harrison Gorman, Harris Arthur (in memoriam),
  Alta McCabe, Margaret Menache, PhD, Alexis
  Kaminsky, PhD Eastern Navajo Health Board
• Thanks to the many others whove contributed

18
Project funding support

• DiNEH project supported through the following
  grants
• NIEHS, RO1 ES014565 R25  ES013208 P30
  ES-012072
• USEPA/ERRG pass through contract with support
  from DHHS/NIH/NCRR 1UL1RR031977-01 

19
Questions?
THANK YOU!