RESUMO
Anti-denatured HLA-Cw antibodies are highly prevalent, whereas anti-native HLA-Cw antibodies seem to lead to random flow cytometry crossmatch results. We aimed to reassess crossmatch prediction for anti-HLA-Cw using 2 types of single antigen flow beads (classical beads and beads with diminished expression of denatured HLA), and to compare the pathogenicity of preformed anti-denatured and anti-native HLA-Cw antibodies in kidney transplantation. We performed 135 crossmatches with sera reacting against donor HLA-Cw (classical beads fluorescence ≥500); only 20.6% were positive. Forty-three (31.6%) were anti-denatured HLA antibodies (beads with diminished expression of denatured HLA fluorescence <300); all were crossmatch negative. The correlation between classical beads fluorescence and the crossmatch ratio was low (ρ = 0.178), and slightly higher with beads with diminished expression of denatured HLA (ρ = 0.289). We studied 52 kidney recipients with preformed anti-HLA-Cw donor-specific antibodies. Those with anti-native HLA antibodies experienced more acute and chronic antibody-mediated rejections (P = .006 and .03, respectively), and displayed a lower graft survival (P = .04). Patients with anti-native HLA-Cw antibodies more frequently had previous sensitizing events (P < .000001) or plausibility of their antibody profile according to known anti-native HLA-Cw eplets (P = .0001). Anti-native but not anti-denatured HLA-Cw antibodies are deleterious, which underscores the need for reagents with diminished expression of denatured HLA.
Assuntos
Transplante de Rim , Citometria de Fluxo , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Antígenos HLA , Teste de Histocompatibilidade , Humanos , Isoanticorpos , Doadores de TecidosRESUMO
HLA-DQA1*02:32 differs from DQA1*02:01:01 by one nucleotide substitution in codon 210 in exon 4.
Assuntos
Alelos , Éxons , Cadeias alfa de HLA-DQ , Sequenciamento de Nucleotídeos em Larga Escala , Teste de Histocompatibilidade , Humanos , Cadeias alfa de HLA-DQ/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Teste de Histocompatibilidade/métodos , Sequência de Bases , Códon , Análise de Sequência de DNA/métodosRESUMO
HLA-DRB1*14:253 differs from DRB1*14:54:01 by one nucleotide substitution in codon 233 in exon 5.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cadeias HLA-DRB1/genética , Alelos , Códon , Éxons/genéticaRESUMO
HLA-DQB1*03:512 differs from DQB1*03:02:01 by one nucleotide substitution in codon 89 in exon 2.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Alelos , Cadeias beta de HLA-DQ/genética , CódonRESUMO
HLA-DRB1*11:324 differs from HLA-DRB1*11:62:02 by one nucleotide substitution in codon 38 in exon 2.
Assuntos
Cadeias HLA-DRB1 , Humanos , Cadeias HLA-DRB1/genética , Sequência de Bases , Alelos , Éxons/genética , CódonRESUMO
HLA-C*06:176:02 differs from HLA-C*06:176:01 by two nucleotide substitutions in codons 236 and 237 in exon 4.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Teste de Histocompatibilidade , Éxons/genética , Análise de Sequência de DNARESUMO
HLA-DRB1*13:03:13 differs from HLA-DRB1*13:03:01:01 by one nucleotide substitution in codon 180 in exon 3.
Assuntos
Cadeias HLA-DRB1 , Humanos , Cadeias HLA-DRB1/genética , Sequência de Bases , Alelos , Éxons/genética , CódonRESUMO
HLA-C*07:02:151 differs from HLA-C*07:02:01:01 by one nucleotide substitution in codon 166 in exon 3.
Assuntos
Alelos , Sequência de Bases , Códon , Éxons , Antígenos HLA-C , Teste de Histocompatibilidade , Análise de Sequência de DNA , Humanos , Antígenos HLA-C/genética , Teste de Histocompatibilidade/métodos , Análise de Sequência de DNA/métodos , Alinhamento de SequênciaRESUMO
HLA-DRB4*01:182 differs from HLA-DRB4*01:03:01:01 by one nucleotide substitution in codon 172 in exon 3.
Assuntos
Alelos , Sequência de Bases , Éxons , Cadeias HLA-DRB4 , Teste de Histocompatibilidade , Análise de Sequência de DNA , Humanos , Teste de Histocompatibilidade/métodos , Análise de Sequência de DNA/métodos , Cadeias HLA-DRB4/genética , Códon , Alinhamento de SequênciaRESUMO
HLA-B*14:121 differs from HLA-B*14:01:01:01 by one nucleotide substitution in codon 319 in exon 6.
Assuntos
Genes MHC Classe I , Antígenos HLA-B , Humanos , Alelos , Teste de Histocompatibilidade , Códon , Antígenos HLA-B/genética , Análise de Sequência de DNARESUMO
HLA-C*05:286 differs from HLA-C*05:01:01:02 by one nucleotide substitution in codon 283 in exon 5.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Teste de Histocompatibilidade , Códon , Análise de Sequência de DNARESUMO
HLA-B*51:394Q differs from HLA-B*51:01:01:05 by one nucleotide substitution in codon 339 in exon 7.
Assuntos
Antígenos HLA-B , Humanos , Alelos , Teste de Histocompatibilidade , Códon , Antígenos HLA-B/genética , Análise de Sequência de DNARESUMO
HLA-C*01:263 differs from HLA-C*01:02:01:01 by one nucleotide substitution in codon 98 in exon 3.
Assuntos
Genes MHC Classe I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Teste de Histocompatibilidade , Códon , Análise de Sequência de DNARESUMO
HLA-DRB4*01:01:12 differs from HLA-DRB4*01:01:01:01 by one nucleotide substitution in codon 175 in exon 3.
Assuntos
Alelos , Sequência de Bases , Éxons , Cadeias HLA-DRB4 , Teste de Histocompatibilidade , Análise de Sequência de DNA , Humanos , Teste de Histocompatibilidade/métodos , Análise de Sequência de DNA/métodos , Cadeias HLA-DRB4/genética , Códon , Alinhamento de SequênciaRESUMO
HLA-B*14:122 differs from HLA-B*14:02:01:01 by one nucleotide substitution in codon 102 in exon 3.
Assuntos
Genes MHC Classe I , Antígenos HLA-B , Humanos , Alelos , Teste de Histocompatibilidade , Códon , Antígenos HLA-B/genética , Análise de Sequência de DNARESUMO
HLA-A*32:177 differs from HLA-A*32:01:01:01 by one nucleotide substitution in codon -16 in exon 1.
Assuntos
Antígenos HLA-A , Nucleotídeos , Humanos , Alelos , Éxons/genética , Análise de Sequência de DNA , Antígenos HLA-A/genéticaRESUMO
HLA-DPB1*1516:01 differs from HLA-DPB1*1229:01 by seven nucleotide substitutions in exon 3.
Assuntos
Sequência de Bases , Humanos , Alelos , Cadeias beta de HLA-DP/genética , Éxons/genéticaRESUMO
HLA-DQA1*01:03:11 differs from HLA-DQA1*01:03:01:02 by one nucleotide substitution in codon 59 in exon 2.
Assuntos
Nucleotídeos , Humanos , Alelos , Cadeias alfa de HLA-DQ/genética , Éxons/genéticaRESUMO
HLA-DRB1*04:04:20 differs from HLA-DRB1*04:04:01:04 by one nucleotide substitution in codon 135 in exon 3.
Assuntos
Nucleotídeos , Humanos , Alelos , Éxons/genética , Cadeias HLA-DRB1/genéticaRESUMO
T-cell mediated rejection (TCMR), de novo anti-HLA donor-specific antibodies (dnDSAs) and ensuing antibody-mediated rejection (ABMR) reduce kidney transplantation (KT) survival. The immunomodulatory effects of 25-hydroxyvitamin D [25(OH)D] could be beneficial for KT outcomes. We aimed to evaluating the association between 25(OH)D levels, the development of dnDSAs, clinical TCMR and ABMR, and graft survival. This single center retrospective study included 253 KT recipients (KTRs) transplanted without preformed DSA between 2010 and 2013. We measured 25(OH)D in successive serum samples: at KT (M0) and M12 for the entire cohort, and additionally at M24 and/or M36 when sera were available. We assessed graft outcomes up to 5 years post-KT. The proportion of KTRs having sufficient 25(OH)D at KT (M0) was high (81.4%) and then dropped at M12 (71.1%). KTRs with sufficient 25(OH)D at M0 experienced less clinical TCMR (HR, 0.41; 95% CI, 0.19-0.88 in multivariate analysis). A sufficient 25(OH)D at M12 was independently associated with a longer dnDSA-free survival (HR, 0.34; 95% CI, 0.17-0.69). There was no association between 25(OH)D and clinical AMBR. Studying the KTRs with 25(OH)D measurements at M12, M24 and M36 (n = 203), we showed that 25(OH)D sufficiency over the 3 first-years post-KT was associated with a longer graft survival in multivariate analyses (HR, 0.39; 95% CI, 0.22-0.70). To our knowledge, this study is the first showing an association between 25(OH)D sufficiency post-KT and dnDSA occurrence in KTRs. Moreover, we reinforce previously published data showing an association between 25(OH)D, TCMR and graft survival in KT.