Characterization of the Novel HLA-C*07:01:126 Allele by Sequencing-Based Typing.

HLA-C*07:01:126 differs from HLA-C*07:01:01:01 by one nucleotide substitution in codon 328 in exon 7.

Characterization of the Novel HLA-A*24:02:169 Allele by Sequencing-Based Typing.

HLA-A*24:02:169 differs from HLA-A*24:02:01:01 by one nucleotide substitution in codon -23 in exon 1.

Characterisation of the novel HLA-C*01:262 allele by sequencing-based typing.

HLA-C*01:262 differs from HLA-C*01:02:01:01 by one nucleotide substitution in codon 150 in exon 3.

Characterisation of the novel HLA-A*26:247 allele by sequencing-based typing.

HLA-A*26:247 differs from HLA-A*26:01:01:01 by one nucleotide substitution in codon 245 in exon 4.

Characterisation of the novel HLA-B*51:411 allele by sequencing-based typing.

HLA-B*51:411 differs from HLA-B*51:01:01:01 by one nucleotide substitution in codon 235 in exon 4.

Characterisation of the novel HLA-DPB1*1618:01 allele by sequencing-based typing.

HLA-DPB1*1618:01 differs from HLA-DPB1*18:01:01:01 by one nucleotide substitution in codon 215 in exon 4.

Characterisation of the novel HLA-DRB1*08:126 allele by sequencing-based typing.

HLA-DRB1*08:126 differs from HLA-DRB1*08:04:01:01 by one nucleotide substitution in codon 152 in exon 3.

Characterisation of the novel HLA-C*07:02:151 allele by sequencing-based typing.

HLA-C*07:02:151 differs from HLA-C*07:02:01:01 by one nucleotide substitution in codon 166 in exon 3.

Lessons from prospective longitudinal follow-up of a French APECED cohort.

BACKGROUND: APECED syndrome is a rare disease caused by biallelic mutations of the AIRE gene, usually presenting with the triad "hypoparathyroidism-adrenal failure-chronic mucocutaneous candidiasis (CMC)" and non-endocrine manifestations. The aim of this study was to determine the molecular profile of the AIRE gene, the prevalence of rare manifestations and to characterize immunological disturbances in a French cohort. PATIENTS AND METHODS: A national, multicenter prospective observational study to collect genetic, clinical, biological and immunological data (NCT03751683). RESULTS: 25 patients (23 families) were enrolled. Eleven distinct AIRE variants were identified, two of which were not previously reported: an intronic variant, c.653-70G > A, and a c.1066del (p.Arg356GlyfsX22) variant (exon 9). The most common was the Finnish variant c.769C > T (16 alleles), followed by the variant c.967_979del13 (15 alleles), which seemed associated with a less severe phenotype. 17/25 patients were homozygote. The median number of clinical manifestations was seven; 19/25 patients presented with the hypoparathyroidism-adrenal failure-CMC triad, 8/13 showed pulmonary involvement, 20/25 had ectodermal dystrophy, 8/25 had malabsorption, and 6/23 had asplenia. Fifteen out of 19 patients had NK cell lymphopenia with an increase in CD4+ and CD8+ T lymphocytes and an age-dependent alteration of B lymphocyte homeostasis compared with matched controls (p < 0.001), related to the severity of the disease. All tested sera (n = 18) were positive for anti-interferon-α, 15/18 for anti-interleukin-22 antibodies, and 13/18 for anti-interleukin-17F antibodies, without clear phenotypic correlation other than with CMC. CONCLUSION: This first prospective cohort showed a high AIRE genotype variability, with two new gene variants. The prevalence of potentially life-threatening non-endocrine manifestations, was higher with systematic screening. These manifestations could, along with age-dependent B-cell lymphopenia, contribute to disease severity. Systematic screening for all the manifestations of the syndrome would allow earlier diagnosis, supporting vaccination, and targeted therapeutic approaches.

Characterization of the novel HLA-B*14:121 allele by sequencing-based typing.

HLA-B*14:121 differs from HLA-B*14:01:01:01 by one nucleotide substitution in codon 319 in exon 6.

Characterization of the novel HLA-C*05:286 allele by sequencing-based typing.

HLA-C*05:286 differs from HLA-C*05:01:01:02 by one nucleotide substitution in codon 283 in exon 5.

Characterization of the novel HLA-B*51:394Q allele by sequencing-based typing.

HLA-B*51:394Q differs from HLA-B*51:01:01:05 by one nucleotide substitution in codon 339 in exon 7.

Characterization of the novel HLA-C*01:263 allele by sequencing-based typing.

HLA-C*01:263 differs from HLA-C*01:02:01:01 by one nucleotide substitution in codon 98 in exon 3.

Characterization of the novel HLA-B*40:539 allele by sequencing-based typing.

HLA-B*40:539 differs from HLA-B*40:01:01 by one nucleotide substitution in codon 46 in exon 2.

Characterization of the novel HLA-C*06:176:02 allele by sequencing-based typing.

HLA-C*06:176:02 differs from HLA-C*06:176:01 by two nucleotide substitutions in codons 236 and 237 in exon 4.

Impact of Preformed Donor-Specific Anti-HLA-Cw and Anti-HLA-DP Antibodies on Acute Antibody-Mediated Rejection in Kidney Transplantation.

Given the risk of rejection, the presence of preformed donor specific antibodies (DSA) contraindicates transplantation in most allocation systems. However, HLA-Cw and -DP DSA escape this censorship. We performed a multicentric observational study, in which the objective was to determinate risk factors of acute antibody-mediated rejection (aABMR) in recipients transplanted with preformed isolated Cw- or DP-DSA. Between 2010 and 2019, 183 patients were transplanted with a preformed isolated Cw- or DP-DSA (92 Cw-DSA; 91 DP-DSA). At 2 years, the incidence of aABMR was 12% in the Cw-DSA group, versus 28% in the DP-DSA group. Using multivariable Cox regression model, the presence of a preformed DP-DSA was associated with an increased risk of aABMR (HR = 2.32 [1.21-4.45 (p = 0.001)]) compared with Cw-DSA. We also observed a significant association between the DSA's MFI on the day of transplant and the risk of aABMR (HR = 1.09 [1.08-1.18], p = 0.032), whatever the DSA was. Interaction term analysis found an increased risk of aABMR in the DP-DSA group compared with Cw-DSA, but only for MFI below 3,000. These results may plead for taking these antibodies into account in the allocation algorithms, in the same way as other DSA.

Characterization of the novel HLA-DPB1*1463:01N allele by sequencing-based typing.

HLA-DPB1*1463:01N differs from HLA-DPB1*02:01:02:04 by one nucleotide substitution in codon 128 in exon 3.

Characterization of the novel HLA-B*44:324:02 allele by sequencing-based typing.

HLA-B*44:324:02 differs from HLA-B*44:324:01 by one nucleotide substitution in codon 99 in exon 3.

Characterization of the novel HLA-C*12:384 allele by sequencing-based typing.

HLA-C*12:384 differs from HLA-C*12:03:01:02 by one nucleotide substitution in codon 42 in exon 2.