Use of DPB1 T-cell epitope algorithm among italian transplant centers: A survey on behalf of Associazione Italiana di Immunogenetica e Biologia dei Trapianti.

The HLA-DPB1 locus has been demonstrated to have a significant role on patients' outcome after allogeneic HSCT, and the so-called T-cell epitope (TCE) algorithm has been incorporated in international guidelines for the selection of unrelated donors. The purpose of the present study is to measure, through a national survey conducted on behalf of the Associazione Italiana di Immunogenetica e Biologia dei Trapianti (AIBT), the extent of awareness and use of HLA-DPB1 TCE-based algorithms during the donor search. 89% of the HLA laboratories answered to a short questionnaire and the results showed a progressive increase of the laboratories typing DPB1 in patients and their potential donors during the search (from 44% to 79% during the 2010-2019 period) as well as the application of a TCE-based algorithm for the donor choice whenever possible (from 24% to 65% during the same period). The DP-permissiveness status is detailed in the official HLA typing report by 12%, 32% and 50% of laboratories in 2010, 2015 and 2019, respectively. The present data indicate an encouraging raise in the awareness of the HLA-DPB1 role in unrelated donor selection; noteworthy, mentioning the TCE-based permissiveness status in the HLA typing report of each potential unrelated donor represents a notable mean to raise awareness among transplant physicians and to support them in their task of choosing the best donor. Nonetheless, despite the compelling evidence of the predictive ability of TCE-based algorithms, further efforts are still needed to extend its application to all transplant centers in Italy.

Consequences of ABO incompatibility in multiple myeloma patients undergoing peripheral blood stem cell transplantation after reduced intensity conditioning.

BACKGROUND: Although the ABO blood group is one of two major antigen systems of relevance for transplantation in humans, there are still conflicting data concerning the influence of ABO-incompatibility on transplant outcome. This study investigated the effect of ABO incompatibility in recipients of haematopoietic progenitor cell transplants from related donors after reduced intensity conditioning (RIC) regimens. MATERIALS AND METHODS: We retrospectively analysed data from 19 multiple myeloma patients included in a prospective RIC allogeneic haematopoietic progenitor cell transplantation protocol, focusing on engraftment, transfusion requirement, Graft-versus-Host Disease, transplant-related mortality and survival. RESULTS: Five out of the 19 patients (26%) received an ABO-incompatible transplant, with minor ABO-mismatch in two patients (10%), major ABO-mismatch in one case (5%), and bidirectional incompatibility in two cases. Neutrophil recovery was not significantly different between the ABO-compatible and ABO-incompatible groups (p=0.85). At 30 days after transplantation, 12 of 19 patients tested (63%) had engraftment with all cells of donor origin (100% chimeric), and continued to be fully chimeric on day 100+ evaluations. Patients with major/bidirectional ABO incompatibility required more red blood cell and platelet units after transplantation and were transfused for longer periods of time, as compared with patients with minor or no ABO incompatibility. Transient, mild haemolysis was noted in one patient between days 10 and 30. Graft-versus-Host Disease, disease progression and transplant-related mortality were not affected by ABO matching. DISCUSSION: Although delayed red blood cell engraftment and increased transfusion requirements were documented, in this study ABO incompatibility after the RIC protocol used did not impair the clinical outcome.

A very rare association of three mutations of the HFE gene for hemochromatosis.

In the present paper, we describe a patient who is a compound heterozygote for three mutations in the HFE gene: C282Y, H63D, and E168Q. The patient's mother carries two copies of H63D and one copy of E168Q; the patient's father is heterozygous for C282Y. The family study indicates that the patient, as well as his sister, a maternal uncle, and a first cousin, all have inherited a single HFE allele that contains two mutations H63D and E168Q. The clinical symptoms and laboratory findings of the patient and his relatives are consistent with the conclusion that the E168Q mutation by itself is unlikely to result in hemochromatosis.

Frequency of the HFE gene mutations in five Italian populations.

Genetic hemochromatosis is an autosomal recessive disorder characterized by iron overload and a variety of clinical manifestations such as liver cirrhosis and arthropathy. It is the most common genetic disease of northern European populations. The principal gene responsible for hereditary hemochromatosis, designated HFE, is located on chromosome 6 in the HLA region. The single point mutation 845A, changing cysteine at position 282 to tyrosine (C282Y), in this gene has been identified as the main genetic basis of hereditary hemochromatosis. Two other mutations, 187G, a histidine to aspartate at amino acid 63 (H63D), and 193T, a serine to cysteine at amino acid 65 (S65C), appear to be associated with milder forms of hereditary hemochromatosis. There is a high prevalence of the C282Y mutation in northern European populations, whereas in those of the Mediterranean basin the prevalence seems low and almost absent in Far East countries. This mutation seems usually to occur on the ancestral haplotype 7.1. Accordingly, a Celtic origin of this mutation has been suggested. The aim of this study was to determine the frequency of HFE gene mutations in five geographic regions in Italy. Samples were tested for C282Y, H63D, and S65C mutations of the HFE gene according to methods of each laboratory and the results were standardized with the exchange of typed samples between the different laboratories. In addition, C282Y-positive DNA samples were typed for D6S105 allele 8 and HLA-A3 by ARMS-PCR. We have found that the allele frequency of the C282Y mutation decreases from northeast Italy (Friuli, 6%) to northwest Italy (Piedmont, 4.8%) and to central Italy (Emilia-Romagna, 1.7%). However, this mutation is lacking in the two regions of the Mediterranean basin's center (Sicily and Sardinia). Accordingly, a significant difference in the frequency of the mutation was observed between these Italian regions (P = 0.07 x 10(-3)). In contrast, no difference was observed in allele frequency of H63D in the five Italian regions. Finally, as regards the S65C mutation a very low frequency was observed in Friuli, Emilia-Romagna, and Sardinia, whereas in Sicily and Piedmont we have not found this mutation. In conclusion, these data are consistent with the hypothesis that the C282Y mutation occurred in Caucasian populations of Celtic origin, whereas the H63D mutation is more ancient as demonstrated by the ubiquitous distribution.