Characterization of the novel HLA-DQA1*01:03:11 allele by sequencing-based typing.

HLA-DQA1*01:03:11 differs from HLA-DQA1*01:03:01:02 by one nucleotide substitution in codon 59 in exon 2.

Resolving unknown nucleotides in the IPD-IMGT/HLA database by extended and full-length sequencing of HLA class I and II alleles.

In the past, identification of HLA alleles was limited to sequencing the region of the gene coding for the peptide binding groove, resulting in a lack of sequence information in the HLA database, challenging HLA allele assignment software programs. We investigated full-length sequences of 19 HLA class I and 7 HLA class II alleles, and we extended another 47 HLA class I alleles with sequences of 5' and 3' UTR regions that were all not yet available in the IPD-IMGT/HLA database. We resolved 8638 unknown nucleotides in the coding sequence of HLA class I and 2139 of HLA class II. Furthermore, with full-length sequencing of the 26 alleles, more than 90 kb of sequence information was added to the non-coding sequences, whereas extension of the 47 alleles resulted in the addition of 5.5 kb unknown nucleotides to the 5' UTR and > 31.7 kb to the 3' UTR region. With this information, some interesting features were observed, like possible recombination events and lineage evolutionary origins. The continuing increase in the availability of full-length sequences in the HLA database will enable the identification of the evolutionary origin and will help the community to improve the alignment and assignment accuracy of HLA alleles.

Characterization of the novel HLA-DQA1*02:01:14 allele by sequencing-based typing.

HLA-DQA1*02:01:14 differs from HLA-DQA1*02:01:01:02 by one nucleotide substitution in codon 105 in exon 3.

Human leukocyte antigen evolutionary divergence influences outcomes of paediatric patients and young adults affected by malignant disorders given allogeneic haematopoietic stem cell transplantation from unrelated donors.

High genetic heterogeneity in the human leukocyte antigen (HLA) increases the likelihood of efficient immune response to pathogens and tumours. As measure of HLA diversity, HLA evolutionary divergence (HED) has been shown to predict the response of tumours to immunotherapy and haematopoietic stem cell transplantation (HSCT) in adults. We retrospectively investigated the association of HED with outcomes of 153 paediatric/young adults patients, treated for malignant disorders with HSCT from 9-10/10 HLA-matched unrelated donors. HED was calculated as pairwise genetic distance between alleles in patient HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1, using the locus median to stratify patients with 'high' or 'low' HED. Patients with high HED-B and -DRB1 showed significantly improved disease-free survival (DFS), especially when combined (70.8% vs 53.7% p = 0.008). High HED-B + -DRB1 was also associated with improved overall survival (OS) (82.1 vs 66.4% p = 0.014), and concomitant reduction of non-relapse-mortality (5.1% vs 21.1% p = 0.006). The impact on OS and DFS of combined HED-B + -DRB1 was confirmed in multivariate analysis [hazard ratio (HR) 0.39, p = 0.009; and HR 0.45, p = 0.007 respectively]. Only high HED scores for HLA-DPB1 were associated, in univariate analysis, with reduced incidence of relapse (15.9% vs 31.1%, p = 0.03). These results support HED as prognostic marker in allogeneic HSCT and, if confirmed in larger cohorts, would allow its use to inform clinical risk and potentially influence clinical practice.

Characterization of the novel HLA-DQA1*05:53 allele by sequencing-based typing.

HLA-DQA1*05:53 differs from HLA-DQA1*05:05:01:01 by one nucleotide substitution in codon 221 in exon 4.

Characterization of the novel HLA-DRB1*11:04:21 allele by sequencing-based typing.

HLA-DRB1*11:04:21 differs from HLA-DRB1*11:04:01 by one nucleotide substitution in codon 69 in exon 2.

Identification of the novel HLA-A*30:181 allele by next-generation sequencing.

HLA-A*30:181 differs from HLA-A*30:01:01 by one nucleotide substitution in Exon 4832 G to A.

Disability assessment using Google Maps.

OBJECTIVES: To evaluate the concordance between Google Maps® application (GM®) and clinical practice measurements of ambulatory function (e.g., Ambulation Score (AS) and respective Expanded Disability Status Scale (EDSS)) in people with multiple sclerosis (pwMS). MATERIALS AND METHODS: This is a cross-sectional multicenter study. AS and EDSS were calculated using GM® and routine clinical methods; the correspondence between the two methods was assessed. A multinomial logistic model is investigated which demographic (age, sex) and clinical features (e.g., disease subtype, fatigue, depression) might have influenced discrepancies between the two methods. RESULTS: Two hundred forty-three pwMS were included; discrepancies in AS and in EDDS assessments between GM® and routine clinical methods were found in 81/243 (33.3%) and 74/243 (30.4%) pwMS, respectively. Progressive phenotype (odds ratio [OR] = 2.8; 95% confidence interval [CI] 1.1-7.11, p = 0.03), worse fatigue (OR = 1.03; 95% CI 1.01-1.06, p = 0.01), and more severe depression (OR = 1.1; 95% CI 1.04-1.17, p = 0.002) were associated with discrepancies between GM® and routine clinical scoring. CONCLUSION: GM® could easily be used in a real-life clinical setting to calculate the AS and the related EDSS scores. GM® should be considered for validation in further clinical studies.

Characterization of the novel HLA-DRB4*01:151 allele by sequencing-based typing.

HLA-DRB4*01:151 differs from DRB4*01:01:01:01 by one nucleotide substitution in codon 178 in exon 3.

Characterization of the novel HLA-DPA1*01:60 allele by sequencing-based typing.

HLA-DPA1*01:60 differs from HLA-DPA1*01:03:01:04 by one nucleotide substitution in codon 224 in exon 4.

Identification of the novel HLA-DRB1*03:01:32 in an Italian patient.

The novel HLA-DRB1*03:01:32 allele differs from HLA-DRB1*03:01:01:01 by one nucleotide substitution in exon 4.

Characterization of the novel HLA-DRB3*03:49 allele by sequencing-based typing.

HLA-DRB3*03:49 differs from DRB3*03:01:01:01 by one nucleotide substitution in codon 191 in exon 4.

Identification of the novel HLA-DPB1*1149:01.

The new allele HLA-DPB1*1149:01 differs from HLA-DPB1*09:01:01 by one nucleotide substitution in Exon 4.

Identification of a new HLA-B*44 allele, HLA-B*44:02:68, by next generation sequencing.

HLA-B*44:02:68 differs from B*44:02:01:01 by one synonmous nucleotide substitution in codon-10 GGG- > GGA.

Characterization of the novel HLA-DRB3*02:02:25 allele by sequencing-based typing.

HLA-DRB3*02:02:25 differs from HLA-DRB3*02:02:01:02 by one nucleotide substitution in codon 116 in exon 3.

Characterization of the novel HLA-DPA1*01:03:16 allele by sequencing-based typing.

HLA-DPA1*01:03:16 differs from HLA-DPA1*01:03:01:03 by one nucleotide substitution in codon 171 in exon 3.

Characterization of the novel HLA-DQA1*01:22 allele by sequencing-based typing.

HLA-DQA1*01:22 differs from HLA-DQA1*01:05:01 by one nucleotide substitution in codon 8 in exon 2.

Identification of the novel HLA-A*01:289 allele in an Italian patient.

The new allele HLA-A*01:289 differs from HLA-A*01:95 by one nucleotide substitution in exon 2.

Characterization of the novel HLA-DQA1*05:14 allele by sequencing-based typing.

HLA-DQA1*05:14 differs from HLA-DQA1*05:05:01:01 by one nucleotide substitution at codon 90 in exon 3.