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2018 ; 3
(5
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
A peripheral blood transcriptomic signature predicts autoantibody development in
infants at risk of type 1 diabetes
#MMPMID29515040
Mehdi AM
; Hamilton-Williams EE
; Cristino A
; Ziegler A
; Bonifacio E
; Le Cao KA
; Harris M
; Thomas R
JCI Insight
2018[Mar]; 3
(5
): ä PMID29515040
show ga
Autoimmune-mediated destruction of pancreatic islet ? cells results in type 1
diabetes (T1D). Serum islet autoantibodies usually develop in genetically
susceptible individuals in early childhood before T1D onset, with multiple islet
autoantibodies predicting diabetes development. However, most at-risk children
remain islet-antibody negative, and no test currently identifies those likely to
seroconvert. We sought a genomic signature predicting seroconversion risk by
integrating longitudinal peripheral blood gene expression profiles collected in
high-risk children included in the BABYDIET and DIPP cohorts, of whom 50
seroconverted. Subjects were followed for 10 years to determine time of
seroconversion. Any cohort effect and the time of seroconversion were corrected
to uncover genes differentially expressed (DE) in seroconverting children. Gene
expression signatures associated with seroconversion were evident during the
first year of life, with 67 DE genes identified in seroconverting children
relative to those remaining antibody negative. These genes contribute to T cell-,
DC-, and B cell-related immune responses. Near-birth expression of ADCY9, PTCH1,
MEX3B, IL15RA, ZNF714, TENM1, and PLEKHA5, along with HLA risk score predicted
seroconversion (AUC 0.85). The ubiquitin-proteasome pathway linked DE genes and
T1D susceptibility genes. Therefore, a gene expression signature in infancy
predicts risk of seroconversion. Ubiquitination may play a mechanistic role in
diabetes progression.
|Autoantibodies/blood/immunology
[MESH]
|Child, Preschool
[MESH]
|Diabetes Mellitus, Type 1/blood/*diagnosis/immunology
[MESH]