Persistent mixed chimerism represents a state in which recipient and donor cells stably co-exist after hematopoietic stem cell transplantation. However, since in most of the studies reported in ...literature the engraftment state was observed in the nucleated cells, in this study we determined the donor origin of the mature erythrocytes of patients with persistent mixed chimerism after transplantation for hemoglobinopathies. Results were compared with the engraftment state observed in singly picked out burst-forming unit - erythroid colonies and in the nucleated cells collected from the peripheral blood and from the bone marrow.
The donor origin of the erythrocytes was determined analyzing differences on the surface antigens of the erythrocyte suspension after incubation with anti-ABO and/or anti-C, -c, -D, -E and -e monoclonal antibodies by a flow cytometer. Analysis of short tandem repeats was used to determine the donor origin of nucleated cells and burst-forming unit - erythroid colonies singly picked out after 14 days of incubation.
The proportions of donor-derived nucleated cells in four transplanted patients affected by hemoglobinopathies were 71%, 46%, 15% and 25% at day 1364, 1385, 1314 and 932, respectively. Similar results were obtained for the erythroid precursors, analyzing the donor/recipient origin of the burst-forming unit - erythroid colonies. In contrast, on the same days of observation, the proportions of donor-derived erythrocytes in the four patients with persistent mixed chimerism were 100%, 100%, 73% and 90%. Conclusions Our results showed that most of the erythrocytes present in four long-term transplanted patients affected by hemoglobinopathies and characterized by the presence of few donor engrafted nucleated cells were of donor origin. The indication that small proportions of donor engrafted cells might be sufficient for clinical control of the disease in patients affected by hemoglobinopathies is relevant, although the biological mechanisms underlying these observations need further investigation.
1 Laboratory of Immunogenetics and Transplant Biology, IME Foundation, Polyclinic of Tor Vergata, Rome
2 International Center for Transplantation in Thalassemia and SCA, IME Foundation, Polyclinic of ...Tor Vergata (PTV), Rome
3 Department of Laboratory Medicine, Polyclinic of Tor Vergata (PTV), Rome
4 Medical Genetics, Exp Medicine Dept, "Sapienza-University of Rome", S. Camillo Hospital, Rome, Italy
Correspondence: Marco Andreani, Ph.D., Laboratorio di Immunogenetica e Biologia dei Trapianti, Fondazione IME, Policlinico Tor Vergata, Viale Oxford 81 00133 Rome. E-mails: m.andreani{at}fondazioneime.org
Hepcidin is a 25-amino acid peptide, derived from cleavage of an 84 amino acid pro-peptide produced predominantly by hepatocytes. This molecule, encoded by the hepcidin antimicrobial peptide ( HAMP ) gene shows structural and functional properties consistent with a role in innate immunity. Moreover, as demonstrated in mice and humans, hepcidin is a major regulator of iron metabolism, and acts by binding to ferroportin and controlling its concentration and trafficking. In this study we investigated the influence that mutations in HAMP and/or hemocromatosis ( HFE ) genes might exert on iron metabolism in a group of poly-transfused thalassemic patients in preparation for bone marrow transplantation. Our results showed that the presence of the c.-582 A>G polymorphism (rs10421768) placed in HAMP promoter (HAMP-P) might play a role in iron metabolism, perhaps varying the transcriptional activation that occurs through E-boxes located within the promoter.
Key words: HAMP, HFE, iron metabolism, liver iron concentration, β-thalassemia.
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Genetic variation in hepcidin expression and its implications for phenotypic differences in iron metabolism
Henry K. Bayele, Surjit Kaila S. Srai
Haematologica 2009 94: 1185-1188.
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In the present study we investigated the role of donor specific HLA antibodies (DSA) and donor KIR repertoire characteristics in a group of 18 patients affected by haemoglobinopathies who underwent ...haploidentical T cell depleted transplantation. Among these patients, 8 rejected the transplant while 10 had complete donor chimerism (CC). Five out of 8 patients (62.5%) who rejected graft had anti-HLA antibodies in the sera collected before transplant, while only 1 patient out of 10 (10%) with CC showed their presence (p=0,042). Notably, of the 5 HLA antibodies positive patients who rejected the graft 3 had DSA (2 for class I and 1 for class I and II) while none of the patients with CC had DSA. Among the 8 patients that experienced graft failure 4 were transplanted with a donor characterized by the lack of NK alloreactivity and 5 with a donor with a B content value <2. Although we analyzed a small cohort of patients, our data indicated that the presence of anti-HLA antibodies in patient sera, but not donor KIR characteristics, correlates with graft failure thus suggesting that analysis of anti-HLA antibodies should be taken into account in haploidentical transplant setting.
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