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2017 ; 8
(ä): 182
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Major Histocompatibility Complex Class I Chain-Related A (MICA) Molecules:
Relevance in Solid Organ Transplantation
#MMPMID28293239
Baranwal AK
; Mehra NK
Front Immunol
2017[]; 8
(ä): 182
PMID28293239
show ga
An ever growing number of reports on graft rejection and/or failure even with
good HLA matches have highlighted an important role of non-HLA antigens in
influencing allograft immunity. The list of non-HLA antigens that have been
implicated in graft rejection in different types of organ transplantation has
already grown long. Of these, the Major Histocompatibility Complex class I
chain-related molecule A (MICA) is one of the most polymorphic and extensively
studied non-HLA antigenic targets especially in the kidney transplantation.
Humoral response to MICA antigens has repeatedly been associated with lower graft
survival and an increased risk of acute and chronic rejection following kidney
and liver transplantation with few studies showing conflicting results. Although
there are clear indications of MICA antibodies being associated with adverse
graft outcome, a definitive consensus on this relationship has not been arrived
yet. Furthermore, only a few studies have dealt with the impact of MICA
donor-specific antibodies as compared to those that are not donor specific on
graft outcome. In addition to the membrane bound form, a soluble isoform of MICA
(sMICA), which has the potential to engage the natural killer cell-activating
receptor NKG2D resulting in endocytosis and degradation of receptor-ligand
interaction complex leading to suppression of NKG2D-mediated host innate
immunity, has been a subject of intense discussion. Most studies on sMICA have
been directed toward understanding their influence on tumor growth, with limited
literature focusing its role in transplant biology. Furthermore, a unique
dimorphism (methionine to valine) at position 129 in the ?2 domain categorizes
MICA alleles into strong (MICA-129 met) and weak (MICA-129 val) binders of NKG2D
receptor depending on whether they have methionine or valine at this position.
Although the implications of MICA 129 dimorphism have been highlighted in
hematopoietic stem cell transplantation, its role in solid organ transplantation
is yet to be explored. This review summarizes the currently available information
on MICA antibodies, soluble MICA, and MICA-129 dimorphism in a setting of solid
organ transplantation.