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Pre-Existing Maternal Antibodies Cause Rapid Prenatal Rejection of Allotransplants in the Mouse Model of In Utero Hematopoietic Cell Transplantation

Riley, John S; McClain, Lauren E; Stratigis, John D; Coons, Barbara E; Li, Haiying; Hartman, Heather A; Peranteau, William H
In utero hematopoietic cell transplantation (IUHCT) is a nonmyeloablative nonimmunosuppressive alternative to postnatal hematopoietic stem cell transplantation for the treatment of congenital hemoglobinopathies. Anti-HLA donor-specific Abs (DSA) are associated with a high incidence of graft rejection following postnatal hematopoietic stem cell transplantation. We determine if DSA present in the mother can similarly cause graft rejection in the fetus following IUHCT. Ten million C57BL/6 (B6, H2kb) bone marrow cells were transplanted in utero into gestational day 14 BALB/c (H2kd) fetuses. The pregnant BALB/c dams carrying these fetuses either had been previously sensitized to B6 Ag or were injected on gestational days 13-15 with serum from B6-sensitized BALB/c females. Maternal-fetal Ab transmission, Ab opsonization of donor cells, chimerism, and frequency of macrochimeric engraftment (chimerism >1%) were assessed by flow cytometry. Maternal IgG was transmitted to the fetus and rapidly opsonized donor cells following IUHCT. Donor cell rejection was observed as early as 4 h after IUHCT in B6-sensitized dams and 24 h after IUHCT in dams injected with B6-sensitized serum. Efficient opsonization was strongly correlated with decreased chimerism. No IUHCT recipients born to B6-sensitized dams or dams injected with B6-sensitized serum demonstrated macrochimeric engraftment at birth compared with 100% of IUHCT recipients born to naive dams or dams injected with naive serum (p < 0.001). In summary, maternal donor-specific IgG causes rapid, complete graft rejection in the fetus following IUHCT. When a third-party donor must be used for clinical IUHCT, the maternal serum should be screened for DSA to optimize the chance for successful engraftment.
PMCID:6103848
PMID: 30021770
ISSN: 1550-6606
CID: 5653382

The impact of redistributing power to disadvantaged families in Hungary

Kósa, K; Coons, B; Molnár, Á
The Commission on Social Determinants of Health (CSDH) formulated recommendations along which health inequalities can be successfully tackled anywhere in the world. The situation of the Roma minority in Europe provides countless opportunities for the translation of these guidelines into action that should be guided by coherent and evidence-based strategies integrating lessons learned in smaller-scale field projects. Our paper describes the long-term evaluation of a locally initiated housing project in Hungary carried out more than a decade after implementation, which highlights the salience of the CSDH's recommendations and critical factors for success and sustainability. The project provides evidence for the long-term positive impact on education of the social housing project implemented by an empowered community through delegating decision making to a board of representatives of the beneficiaries in all decisions, including financial ones. Educational level greatly improved, and all houses–inhabited by 17 out of 20 families who initially entered the project—remained in good condition, properly equipped and decorated after 13 years of implementation, in spite of an increase of unemployment during the same period which led to reduced income and deterioration of the families' economic situation. Better housing conditions for vulnerable people can be sustained and result in increased educational level if incremental improvement is aimed for and coupled with the redistribution of power at the local level.
PMID: 28180260
ISSN: 1460-2245
CID: 5653372