ABSTRACT
HLA-DRB4*01:01:12 differs from HLA-DRB4*01:01:01:01 by one nucleotide substitution in codon 175 in exon 3.
Subject(s)
Alleles , Base Sequence , Exons , HLA-DRB4 Chains , Histocompatibility Testing , Sequence Analysis, DNA , Humans , Histocompatibility Testing/methods , Sequence Analysis, DNA/methods , HLA-DRB4 Chains/genetics , Codon , Sequence AlignmentABSTRACT
HLA-DQA1*01:03:11 differs from HLA-DQA1*01:03:01:02 by one nucleotide substitution in codon 59 in exon 2.
Subject(s)
Nucleotides , Humans , Alleles , HLA-DQ alpha-Chains/genetics , Exons/geneticsABSTRACT
HLA-DRB1*04:04:20 differs from HLA-DRB1*04:04:01:04 by one nucleotide substitution in codon 135 in exon 3.
Subject(s)
Nucleotides , Humans , Alleles , Exons/genetics , HLA-DRB1 Chains/geneticsABSTRACT
HLA-B*14:121 differs from HLA-B*14:01:01:01 by one nucleotide substitution in codon 319 in exon 6.
Subject(s)
Genes, MHC Class I , HLA-B Antigens , Humans , Alleles , Histocompatibility Testing , Codon , HLA-B Antigens/genetics , Sequence Analysis, DNAABSTRACT
HLA-C*05:286 differs from HLA-C*05:01:01:02 by one nucleotide substitution in codon 283 in exon 5.
Subject(s)
Genes, MHC Class I , HLA-C Antigens , Humans , HLA-C Antigens/genetics , Alleles , Histocompatibility Testing , Codon , Sequence Analysis, DNAABSTRACT
HLA-B*51:394Q differs from HLA-B*51:01:01:05 by one nucleotide substitution in codon 339 in exon 7.
Subject(s)
HLA-B Antigens , Humans , Alleles , Histocompatibility Testing , Codon , HLA-B Antigens/genetics , Sequence Analysis, DNAABSTRACT
HLA-C*01:263 differs from HLA-C*01:02:01:01 by one nucleotide substitution in codon 98 in exon 3.
Subject(s)
Genes, MHC Class I , HLA-C Antigens , Humans , HLA-C Antigens/genetics , Alleles , Histocompatibility Testing , Codon , Sequence Analysis, DNAABSTRACT
HLA-DRB3*02:194 differs from HLA-DRB3*02:02:01:02 by one nucleotide substitution in codon 78 in exon 2.
Subject(s)
Base Sequence , Humans , HLA-DRB3 Chains/genetics , Alleles , Histocompatibility Testing , Codon , Sequence Analysis, DNA , HLA-DRB1 ChainsABSTRACT
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.
Subject(s)
Kidney Transplantation , Vitamin D/analogs & derivatives , Humans , Retrospective Studies , Risk Factors , HLA Antigens , Alleles , Antibodies , Graft Rejection , IsoantibodiesABSTRACT
HLA-C*16:98:02 differs from HLA-C*16:98:01 by one nucleotide substitution in codon 132 in exon 3.
Subject(s)
Genes, MHC Class I , HLA-C Antigens , Humans , HLA-C Antigens/genetics , Alleles , Histocompatibility Testing , Codon , Sequence Analysis, DNAABSTRACT
HLA-B*39:06:09 differs from HLA-B*39:06:02:01 by one nucleotide substitution in codon 135 in exon 3.
Subject(s)
Genes, MHC Class I , HLA-B Antigens , Humans , Alleles , Histocompatibility Testing , Codon , HLA-B Antigens/genetics , Sequence Analysis, DNAABSTRACT
HLA-B*40:539 differs from HLA-B*40:01:01 by one nucleotide substitution in codon 46 in exon 2.
Subject(s)
Genes, MHC Class I , HLA-B Antigens , Humans , Alleles , Histocompatibility Testing , Codon , HLA-B Antigens/genetics , Sequence Analysis, DNAABSTRACT
HLA-C*06:176:02 differs from HLA-C*06:176:01 by two nucleotide substitutions in codons 236 and 237 in exon 4.
Subject(s)
Genes, MHC Class I , HLA-C Antigens , Humans , HLA-C Antigens/genetics , Alleles , Histocompatibility Testing , Exons/genetics , Sequence Analysis, DNAABSTRACT
Granulomatous disease is a serious complication of common variable immunodeficiency (CVID-GD) that occurs in 8-22% of these patients and can mimic sarcoidosis, with which it shares certain clinical, biological, and radiological features. However, few studies to date have compared the two pathologies immunologically and histologically. Therefore, we analyzed the immunological-histological findings for different tissue samples from ten patients with CVID-GD and compared them to those of biopsy-proven sarcoidosis. Specifically, we wanted to know whether or not the signaling abnormalities observed in sarcoidosis granulomas are also present in CVID-GD. Morphological differences were found between CVID-GD histology and classical sarcoidosis: mainly, the former's notable lymphoid hyperplasia associated with granulomas not observed in the latter. All CVID-GD involved organs contained several follicular helper-T (TFH) cells within the granulomatosis, while those cells were inconstantly and more weakly expressed in sarcoidosis. Moreover, CVID and sarcoidosis granulomas expressed the phosphorylated-signal transducer and activator of transcription (pSTAT)1 and pSTAT3 factors, regardless of the organ studied and without any significant difference between entities. Our results suggest that the macrophage-activation mechanism in CVID resembles that of sarcoidosis, thereby suggesting that Janus kinase (JAK)-STAT-pathway blockade might be useful in currently difficult-to-treat CVID-GD.
Subject(s)
Common Variable Immunodeficiency , Sarcoidosis , Humans , Common Variable Immunodeficiency/complications , Sarcoidosis/complications , Granuloma/etiology , Biopsy , Signal TransductionABSTRACT
ABSTRACT: Chronic graft-versus-host disease (cGVHD) is a debilitating, autoimmune-like syndrome that can occur after allogeneic hematopoietic stem cell transplantation. Constitutively activated B cells contribute to ongoing alloreactivity and autoreactivity in patients with cGVHD. Excessive tissue damage that occurs after transplantation exposes B cells to nucleic acids in the extracellular environment. Recognition of endogenous nucleic acids within B cells can promote pathogenic B-cell activation. Therefore, we hypothesized that cGVHD B cells aberrantly signal through RNA and DNA sensors such as Toll-like receptor 7 (TLR7) and TLR9. We found that B cells from patients and mice with cGVHD had higher expression of TLR7 than non-cGVHD B cells. Using ex vivo assays, we found that B cells from patients with cGVHD also demonstrated increased interleukin-6 production after TLR7 stimulation with R848. Low-dose B-cell receptor (BCR) stimulation augmented B-cell responses to TLR7 activation. TLR7 hyperresponsiveness in cGVHD B cells correlated with increased expression and activation of the downstream transcription factor interferon regulatory factor 5. Because RNA-containing immune complexes can activate B cells through TLR7, we used a protein microarray to identify RNA-containing antigen targets of potential pathological relevance in cGVHD. We found that many of the unique targets of active cGVHD immunoglobulin G (IgG) were nucleic acid-binding proteins. This unbiased assay identified the autoantigen and known cGVHD target Ro-52, and we found that RNA was required for IgG binding to Ro-52. Herein, we find that BCR-activated B cells have aberrant TLR7 signaling responses that promote potential effector responses in cGVHD.
Subject(s)
Bronchiolitis Obliterans Syndrome , Nucleic Acids , Humans , Mice , Animals , Toll-Like Receptor 7/metabolism , Receptors, Antigen, B-Cell/metabolism , RNA , Immunoglobulin GABSTRACT
Our objective was to calculate an immunosuppressant possession ratio (IPR) to diagnose non-adherence at the time of antibody-mediated rejection (ABMR). IPR was defined as the ratio of number of pills collected at the pharmacy to the number of pills prescribed over a defined period. In a first cohort of 91 kidney transplant recipients (KTRs), those with an IPR < 90% had more frequently a tacrolimus through level coefficient of variation >30% than patients with an IPR = 100% (66.7% vs. 29.4%, p = 0.05). In a case-control study, 26 KTRs with ABMR had lower 6 months IPRs than 26 controls (76% vs. 99%, p < 0.001). In KTRs with ABMR, non-adherence was more often diagnosed by a 6 months IPR < 90% than by clinical suspicion (73.1% vs 30.8%, p = 0.02). In the multivariable analysis, only de novo DSA and 6 months IPR < 90% were independently associated with ABMR, whereas clinical suspicion was not (odds ratio, 4.73; 95% CI, 1.17-21.88; p = 0.03; and odds ratio, 6.34; 95% CI, 1.73-25.59; p = 0.007, respectively). In summary, IPR < 90% is a quantifiable tool to measure immunosuppressant non-adherence. It is better associated with ABMR than clinical suspicion of non-adherence.
Subject(s)
Immunosuppressive Agents , Kidney Transplantation , Humans , Immunosuppressive Agents/therapeutic use , Case-Control Studies , Pharmacists , Antibodies , Graft Rejection/prevention & control , Graft Rejection/diagnosis , IsoantibodiesABSTRACT
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.
Subject(s)
Kidney Transplantation , Humans , Antibodies , Graft Rejection , Graft Survival , Histocompatibility Testing , HLA Antigens , Kidney Transplantation/adverse effects , Tissue DonorsABSTRACT
HLA-DRB3*02:192 differs from DRB3*02:02:01:02 by one nucleotide substitution in codon 204 in exon 4.
ABSTRACT
HLA-DPA1*01:159 differs from HLA-DPA1*01:03:01:03 by one nucleotide substitution in codon 120 in exon 3.
Subject(s)
HLA-DP alpha-Chains , Humans , Alleles , Sequence Alignment , Histocompatibility Testing , HLA-DP alpha-Chains/genetics , Sequence Analysis, DNAABSTRACT
HLA-DRB1*11:01:01:12N differs from HLA-DRB1*11:01:01:03 by one nucleotide substitution in intron 3 at position c.652+1G>C, hg19.