[CIS PIDD] [cis-pidd] Foetomaternal interface problems in DiGeorge Syndrome

[CIS-PIDD]

​Dear All
Any reflections or comments on this query are welcomed:
*Our lab has received and analysed placenta from a TOP at 19.3 weeks for
Di-George syndrome.  It shows perivillous fibrin deposition/chronic
histiocytic intervillousitis for which we cannot find a reference in the
literature. Given that DiGeorge syndrome often has T-cell immunity problems
and CHIV/PVFD and villitis of unknown etiology (VUE) are a group of
conditions whose pathogenesis is believed to involve disturbance of immune
tolerance at the fetomaternal interface, we wondered whether there could be
a link. *

*The question raises the issue of whether the shaping of the maternofoetal
interface is adversely influenced by a foetus with incomplete T cell
function. I wondered about a proposed pathogenic pathway such as
this:"Early during implantation, the decidua is invaded by trophoblastic
cells expressing HLA-C, a ligand for the immunoglobulin receptor (KIR) on
the uterine natural killer cells (uNK). The uNK provide regulation of the
neovascularization of the decidua, via proangiogenic and endothelial
factors, which in turn modulate the spiral arteries. When executed
correctly, this process guarantees proper blood flow to the developing
fetus, whilst at the same time reducing alloimmune tendencies towards
foetal rejection. However, to be successful, this tolerance process at the
maternofoetal interface requires assistance from other immune effectors,
such as T regulatory cells, and a relative defect in foetally-derived Treg
function may result in a skewed balance away from an adaptive tolerogenic
immune response towards a pathogenic reaction such as that seen with the
diffuse infiltration of mononuclear cells  of maternal origin into the
placental intervillous space of CHIV, culminating in severe intrauterine
growth restriction, miscarriage or stillbirth. I thought that analysis of
placental tissue for foetal-derived t regs might be of interest. Any other
thoughts? "*
*Regards*
*A/Prof Glenn Reeves*
*Immunologist/Immunopathologist*
*John Hunter Hospital / University of Newcastle*
*NSW Australia*

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