Pretransplantation fetal-maternal microchimerism in pediatric liver transplantation from mother

Abstract

AIMTo investigate the rates of pretransplantation fetal-maternal microchimerism (MC) and its effect on rejection in children receiving maternal liver grafts.METHODSDNA or blood samples before liver transplantation (LT) were available in 45 pediatric patients and their mothers. The presence of pretransplantation MC to non-inherited maternal antigens (NIMAs) (NIMA-MC) in the peripheral blood was tested using nested PCR-single-strand conformation polymorphism analysis for the human leukocyte antigen (HLA)-DRB1 alleles. NIMA-MC was successfully evaluated in 26 of the 45 children. Among these 45 pediatric LT recipients, 23 children (51.1%) received transplants from maternal donors and the other 22 from non-maternal donors.RESULTSAmong these 26 children, pretransplantation NIMA-MC was detected in 23.1% (n = 6), 6.1 (range, 0.8-14) years after birth. Among the children with a maternal donor, the rate of biopsy-proven cellular rejection (BPCR) was 0% in patients with NIMA-MC positivity (0/3) and those with HLA-DR identity with the mother (0/4), but it was 50% in those with NIMA-MC negativity (5/10). Patients with NIMA-MC positivity or HLA-DR identity with the mother showed significantly lower BPCR rate compared with NIMA-MC-negative patients (0% vs 50%, P = 0.04). NIMA-MC-positive patients tended to show lower BPCR rate compared with NIMA-MC-negative patients (P = 0.23).CONCLUSIONThe presence of pretransplantation NIMA-MC or HLA-DR identity with the mother could be associated with BPCR-free survival in pediatric recipients of LT from maternal donors.

Immunologic benefit of maternal donors in pediatric living donor liver transplantation

“…51 Interestingly, this very tolerance to NIMA that potentially resulted in biliary damage may also modulate the offspring's adaptive immune response, resulting in maternal graft immunologic benefit post-LT. 51 While this concept has yet to be investigated directly in maternal donor LDLT, a small study has corroborated that the presence of pretransplant NIMA in the peripheral blood was associated with significantly reduced rates of biopsy-proven rejection in pediatric recipients of maternal grafts. 19 In this study, there was no difference in the age of transplant in NIMA-positive compared to NIMA-negative recipients to suggest that timing between birth and transplantation plays a role in maternal tolerance. 19…”

“…19 In this study, there was no difference in the age of transplant in NIMA-positive compared to NIMA-negative recipients to suggest that timing between birth and transplantation plays a role in maternal tolerance. 19…”

“…More recently, several groups have reported an unexpected finding: improved graft and patient survival in pediatric recipients of maternal living donor liver allografts (Table ) . This is in contrast to modern era observations in kidney transplantation, in which maternal living donor allografts have been associated with worse outcomes .…”

“…16 More recently, several groups have reported an unexpected finding: improved graft and patient survival in pediatric recipients of maternal living donor liver allografts (Table 1). [17][18][19][20][21] This is in contrast to modern era observations in kidney transplantation, in which maternal living donor allografts have been associated with worse outcomes. 22 However, the lower rate of graft survival in maternal kidney transplantation could be attributed to non-immunologic donor-related factors such as smaller graft size and nephron underdosing as observed in prior studies of donor-recipient sex-mismatched allografts.…”

Maternal and Fetal Immune Response to In Utero Stem Cell Transplantation

“…In addition to alloantibodies, maternal cell microchimerism resulting from maternal→fetal cellular trafficking may also be a source of graft rejection in prenatal transplants. Bi-directional cellular trafficking has been recognized to occur in normal pregnancy(17, 18) and the clinical implications of maternal microchimerism in tolerance to solid organ transplantation(19, 20), autoimmunity and bone marrow transplantation have been described (21, 22). More recently, maternal microchimerism was demonstrated to play a pivotal role in promoting cross-generational reproductive fitness thereby providing a rationale for the natural persistence of this phenomenon (23).…”