Allelic and haplotypic HLA frequency distribution in Spanish hematopoietic patients. Implications for unrelated donor searching

Abstract

Histocompatibility criteria for unrelated donor selection are based on high-resolution definition of HLA genes. In spite of the expansion of the unrelated donor registries, HLA matching remains a problem for many patients because of the great diversity of HLA alleles and haplotypes. The availability of matched donors at an allelic level depends on the frequency of the patient's alleles and haplotypes. Therefore, data regarding HLA distribution for each population are needed in order to evaluate the donor searching approach and, may be, even the therapeutic strategy. In the present report, we have analyzed 253 haematological Spanish patients awaiting unrelated haematopoietic stem cell (HSC) donors. HLA allele and haplotype frequencies have been defined at high resolution for the first time in this population. Significant differences in HLA distribution have been reported when comparing two patient groups, one that received full-match (10/10) unrelated donors and one that did not. Factors like rare alleles, presence of B*510101 (because of the association with multiple HLA-C alleles), as well as infrequent B-C and DRB1-DQB1 associations, showed a negative value for finding a suitable donor, whereas the presence of one of the six-gene haplotypes with a frequency ≥ 0.9% in our sample was a positive factor influencing donor searching. These differences will be useful in donor searching advising and in the use of different therapeutic strategies.

Host Genetic Factors in Susceptibility to Herpes Simplex Type 1 Virus Infection: Contribution of Polymorphic Genes at the Interface of Innate and Adaptive Immunity

“…1). Stratification of asymptomatic donors for presence or absence of HSV-1-specific Abs showed that HLA-A*02 was underrepresented solely in seronegative individuals (37.3%), whereas seropositive asymptomatic and symptomatic donors all had A*02 frequencies (52.1 and 49.4%, respectively) similar to those reported in Spanish individuals (45,46), but that difference was only close to significance (p = 0.072 for the comparison between HSV-1 seronegatives and all other donors). Comparison of the HLA allele distribution in the four subgroups of patients showed no other significant differences (Supplemental Table II).…”

“…Similarly, we have not considered quantitative differences in the affinity of KIR2DL2 for various HLA-C1, and even -C2, ligands (64). Of note in the latter regard, C*15:02, the predominant C*15 allele in Spain (46,52), encodes a C2 epitope for which KIR2DL2 lacks affinity, and it is recognized with average affinity by KIR2DL1 (64); functional effects of this interaction (e.g., inhibition, education) are yet to be defined. Current data thus provide no clues to understand a possible NK cell-mediated mechanism underlying the observed association of C*15 with HSV-1 infection.…”

A novel non-rapid-eye movement and rapid-eye-movement parasomnia with sleep breathing disorder associated with antibodies to IgLON5: a case series, characterisation of the antigen, and post-mortem study

“…The chronic clinical course in six patients, the lack of response to immunotherapy despite decrease of the antibody levels, and the neuropathological features would favor a primary neurodegenerative disorder. On the other hand, the frequency of HLA-DRB1*1001 and DQB1*0501 among the Spanish population is 1.6% and 14.4%, 24 arguing that the association noted in all four patients with these alleles represents a genetic susceptibility for autoimmune disease.…”

“…Several findings establish this disorder as a new entity, 1) the characteristic sleep disorder identified in the first three patients by investigators in the Sleep Disorders Unit (masked of information regarding autoantibodies), and in the other five patients by investigators in the Neuroimmunology Laboratory (masked of clinical information)after searching for cases with antibodies similar to those found in the three index patients, 2) the demonstration that patients’ antibodies recognized the same neuronal cell surface antigen (IgLON5), 3) the identification that all patients’ IgLON5 antibodies were mainly IgG4, an isotype considered involved in anti-inflammatory responses, 22 although in some disorders they can be pathogenic, 23 4) the demonstration in 4/4 patients of the same HLA DRB1*1001 and DQB1*0501 alleles which are uncommon among the Spanish population, 24 and 5) the presence of similar neuropathology in two patients, suggesting a novel tauopathy with predominant brainstem and hypothalamic involvement.…”

Clinical manifestations of the anti-IgLON5 disease

“…To calculate the risk ratio of the HLA-DRB1*10:01 and HLA-DQB1*05:01 alleles and the development of the anti-IgLON5 disease we compared the frequency of these alleles in the 15 HLA typed patients with the anti-IgLON5 disease and in the Spanish population that presents a similar allele frequency to other Caucasian populations (allelefrequencies.net). 4 Standard protocol approvals, registrations, and patient consents. The ethics committee of the Hospital Clinic approved the study.…”