Influence of the HLA characteristics of Italian patients on donor search outcome in unrelated hematopoietic stem cell transplantation

Abstract

The information regarding the probability of finding a matched unrelated donor (MUD) within a relatively short time is crucial for the success of hematopoietic stem cell transplantation (HSCT), particularly in patients with malignancies. In this study, we retrospectively analyzed 315 Italian patients who started a search for a MUD, in order to assess the distribution of human leukocyte antigen (HLA) alleles and haplotypes in this population of patients and to evaluate the probability of finding a donor. Comparing two groups of patients based on whether or not a 10/10 HLA-matched donor was available, we found that patients who had a fully-matched MUD possessed at least one frequent haplotype more often than the others (45.6% vs 14.3%; P = 0.000003). In addition, analysis of data pertaining to the HLA class I alleles distribution showed that, in the first group of patients, less common alleles were under-represented (20.2% vs 40.0%; P = 0.006). Therefore, the presence of less frequent alleles represents a negative factor for the search for a potential compatible donor being successful, whereas the presence of one frequent haplotype represents a positive predictive factor. Antigenic differences between patient and donor observed at C and DQB1 loci, were mostly represented by particular B/C or DRB1/DQB1 allelic associations. Thus, having a particular B or DRB1 allele, linked to multiple C or DQB1 alleles, respectively, might be considered to be associated with a lower probability of a successful search. Taken together, these data may help determine in advance the probability of finding a suitable unrelated donor for an Italian patient.

The increase of the global donor inventory is of limited benefit to patients of non-Northwestern European descent

“…A similar observation was reported by Testi et al, 27 who identified a 9/10-or 10/10-matched donor for 75% of their 315 patients, who had a high frequency allele. In contrast Grubic et al 28 reported having found a 9/10-or 10/10-matched donor for 95% of 105 Croatian patients, but their cohort only consisted of patients who were actually transplanted.…”

ERAP1 Regulates Natural Killer Cell Function by Controlling the Engagement of Inhibitory Receptors

“…44), and enter into ER as NH 2 terminal-extended precursors that are trimmed before assembly with MHC-I molecules (26,29,37). The MHC-I consensus motif with a proline at position 2 accounts for mouse L d and more than 33% and 36% of all known human HLA-B and HLA-C motifs in the Italian population (45). Thus, one third of individuals carrying these HLA class I alleles will react with reduced surface expression upon ERAP1 inhibition.…”

Endoplasmic reticulum aminopeptidase 1 function and its pathogenic role in regulating innate and adaptive immunity in cancer and major histocompatibility complex class I‐associated autoimmune diseases

“…Like MHC class I, TAP prefers peptides with hydrophobic or basic residues at the carboxy ends, and transports peptides with proline at position 2 inefficiently . However, since over 33% and 36% of all known human leukocyte antigen (HLA)‐B and HLA‐C alleles in the Caucasian population bind peptides with proline in position 2 (Table ) , it is plausible that these epitopes gain access to the ER as longer precursors with additional N‐terminal flanking residues that will be removed before assembly with HLA class I molecules. Consistent with this hypothesis, ERAP1 and ERAP2 poorly trim proline residue at position 2 causing an accumulation of peptides with these characteristics .…”