RESUMO
El microquimerismo humano se define como la presencia dentro de un individuo de una pequeña población de células originadas en un individuo genéticamente distinto. El microquimerismo adquirido de forma natural se desarrolla a lo largo del embarazo, como una consecuencia del ampliamente demostrado tráfico bidireccional transplacentario de células. Esta trasferencia resulta en un estado microquimérico a décadas posparto, tanto para la madre (microquimerismo fetal) como para su progenie (microquimerismo materno). Aún más, el establecimiento de esta condición ocurre, iatrogénicamente, posterior al transplante de órganos y la transfusión de sangre. Actualmente el microquimerismo es un tema de gran interés alrededor del mundo, dadas sus múltiples posibles implicaciones en la salud y en la enfermedad. Su estudio comenzó a raíz del potencial para el desarrollo de técnicas de diagnóstico prenatal no invasivo, en le presente se tienen amplias expectativas de su utilidad en la terapia con células madre. Se ha propuesto que el microquimerismo podría estar implicado en la patogénesis de ciertas enfermedades autoinmunes, en la preparación de tejidos, el cáncer y la inducción de tolerancia...
Assuntos
Humanos , Doenças Autoimunes , Compartimento Celular , Movimento Celular , Genoma Humano , Placenta , Diagnóstico Pré-Natal , Células-Tronco , Costa RicaRESUMO
Remarkable achievements have been made for lymphocyte infusion of lymphoma and leukemia, especially of lymphoproliferative disease within twenty-first century. The donor lymphocyte infusion or mobilized donor lymphocyte infusion (DLI/DSI) offer an opportunity of second remission for relapse patients post-transplantation. Cytokine-induced killer/DC cytokine-induced killer play an anti-tumor activity beyond non-MHC restricted. Cytotoxic lymphocyte infusion activated by synthetic tumor antigen produces targeted effects of anti-tumor. Transgenic CTL of anti-tumor TCR has brought the dawn in lymphoma and leukemia patients with defective lymphocytes. Maternal lymphocyte infusion play an anti-tumor/viral activity by avoiding the immune barrier of HLA mismatch.
RESUMO
Objective To study the effect of feto-matemal microchimerism in the treatment of activated human leukocyte antigen (HLA) haploidentical mobilized peripheral blood cells against solid tumors. Methods Genomic DNA samples of 25 pairs of HLA haploidentical donors and recipients were extracted. The donor-derived HLA-DRB loci were detected with nested PCR-sequence specific primer(SSP) typing. The mixed lymphocyte proliferation action between the patients and respective donors, the engraftment of donor's cells and the serum levels of Th1/Th2 type of cytokines were measured with MTT,FISH and EIJSA method respectively. The survival time of patients with or without feto-matemal microchimerism were compared as well. Results Using nested PCR-SSP typing, the positive rates of feto-maternal microchimerism in the 25 pairs of HLA haploidentical donors and recipients were 40% in the maternal/children pairs and 0 in the paternal/children pairs. The chimerism positive patients showed less proliferation activity when cocultured with respective donors as compared with unrelated ones (P=0.03).Only one chimerism positive patient experienced the engraft of donor's cell 3 months after treatment as the donor derived XX chromosome was identified with FISH. When the data of chimerism positive patients were deleted, the serum levels of IFNγ 1 month after treatment dropped dramatically from 171.4 (26. 3～258.4) ng/L to 29. 4(1.2～39.9)ng/L. The survival time in chimerism positive patients of the maternal/children pairs was significantly longer than that in chimerism negative patients, which was (31.2±4. 3) months and (11.1±3.3) months, respectively (P=0.036). Conclusion Feto-maternal microchimerism might induce anergy in the HLA haploidentical donors, favor the engraftment of donor's progenitors and maintenance of positive microenvironment and prolong the survival time.