B1060 - Genes and Mechanisms in Type 1 Diabetes - 20/10/2010

B number: 
B1060
Principal applicant name: 
Dr John Todd (University of Cambridge, UK)
Co-applicants: 
Title of project: 
Genes and Mechanisms in Type 1 Diabetes.
Proposal summary: 

As part of our ongoing research into the soluble form of the interleukin-2 receptor alpha (sIL-2RA) and

type 1 diabetes (T1D) risk, we would like to measure sIL-2RA in plasma or serum of ALSPAC children

aged 7, 9 and 11 years old. This would provide the sIL-2RA measurements that we currently lack in

controls subjects. We would measure sIL-2RA in all available samples, or at least 500 samples per age

group. In particular, we would like to measure sIL-2RA in the 500 ALSPAC children bled at the 7, 9 and

11 year clinics, as this would be informative about how well the levels of sIL-2RA tracked in children,

that is, are children in the lower quartile for levels of sIL-2RA at 7 years old, more likely to be in the

lower quartile at subsequent assessments?

We have measured concentrations of sIL-2RA in plasma of 6,000 T1D patient (almost all under age 17

yrs) and 6,000 adult control samples using a reproducible and sensitive immunoassay. In control

subjects, sIL-2RA concentration does not increase with age at sample acquisition (age range 17-69) and

we would like to know whether children have similar concentrations of sIL-2RA. Currently, our data

indicate that T1D children have higher levels of sIL-2RA than adults and this is associated with age-atdiagnosis.

The exciting possibility, which we want to explore further, is the circulating sIL-2RA

concentration maybe a biomarker of T1D diagnosis.

Concentrations of sIL-2RA will be estimated using a commercially available sIL-2RA immunoassay,

OptEIA(tm) Human sIL-2R ELISA (BD Biosciences), with dissociation-enhanced lanthanide

fluoroimmunoassay (DELFIA) detection reagents. Duplicate dilutions of plasma and sera will be assayed

on the same 96 well plate containing a standard curve of recombinant human sIL-2RA. A minimum of 24

micro-l of plasma or sera is required for each sIL-2RA concentration estimate. However, we would like to

receive greater than 30 micro-l to allow for dead volume. We would require information on sex, body mass index (BMI),

age at sample acquisition, T1D status and age at T1D diagnosis information. Also, if asthma/allergy

status is recorded on the questionnaire this might affect sIL-2RA levels.

We would also like to apply for access to the circulating levels of vitamin D [25(OH)D] measured in

ALSPAC children aged 7, 9 and 11 years. The repeat 25(OH)D measures in about 500 ALSPAC children

would be informative about how well levels of 25(OH)D tracked in children. Also, the levels of

25(OH)D in ALSPAC children would be a useful population reference for our T1D patients with

25(OH)D measured. In addition to the 25(OH)D measurements, we would require sex, BMI, age at

sample acquisition, month of sample acquisition, year of sample acquisition, T1D status and age at T1D

diagnosis information.

Date proposal received: 
Wednesday, 20 October, 2010
Date proposal approved: 
Wednesday, 20 October, 2010
Keywords: 
Diabetes, Genetics
Primary keyword: