ashley moffett: new approaches to maternal mortality in africa
TRANSCRIPT
How does the mother’s immune system affect the outcome of
pregnancy?
Ashley Moffett
The Norwegian Mother-Baby study
A cohort consisting of ~800 000 pregnancies
The Norwegian MoBa study
A cohort consisting of ~800 000 pregnancies
The Norwegian MoBa study
A cohort consisting of ~800 000 pregnancies
Pre-eclampsiaStillbirthPrematurity
The Norwegian MoBa study
A cohort consisting of ~800 000 pregnancies
ObstructedlabourHaemorrhageSepsis
Obstructedlabour
William Smellie‘s Sett of Anatomical Tables, 1752
“Perhaps the most clear-cut example of a human character subject to stabilizing (balancing)
selection is birth weight”from Cavalli-Sforza, L.L. &Bodmer, W.F. In The genetics of human populations (Freeman Press, San Francisco, 1971).
(n=13,730)
Birth weight and neonatal mortality rate
The maternal-fetal interface
NK cells and the success of human pregnancy
Failure of invasion of extravillous trophoblast cells in pre-eclampsia
Moffett
The immune system has evolved to discriminate between
self & non-self
Recipient immune cell
Transplantation
self
self label
non-self
non-self labelreceptor
Maternal immune cellPaternalnon-selflabel
Maternalselflabel
Pregnancy
self & non-self labels = HLA
Failure of invasion of extravillous trophoblast cells in pre-eclampsia
Moffett
Uterine NK cells Placenta
Maternal population
NK cells
Paternalnon-selflabels onplacenta
Placenta
NK cells
Placenta
NK cells
Placenta
Risk
NK cells
HLA-C2
HLA-C*07:02 = C1 group
9.0
0.0
58.7
18.0
30.0
(%)
Distribution of Neanderthal HLA-C*0702 allele (group C1) in modern populations
Abi-Rached et alScience 2011
Inverse correlation in human populations between C2 epitope and KIR A haplotype.
Parham 2012. Extending Hiby et al 2004, JEM.
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
0 1000 2000 3000 4000 5000 6000 7000 8000
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
0 1000 2000 3000 4000 5000 6000 7000 8000
Birth weight (grams)
Birth weight frequency
Neonate transfer frequency
The distributions of birth weight and transfer to neonatal special care units.1999-2009 Norway (MoBa)
% f
req
uen
cy