Citations

ABSTRACT The novel HLA‐DQA1*01:217 allele differs from DQA1*01:01:01:12 by a single non‐synonymous change in exon 3′.

ABSTRACT HLA‐C*03:760 differs from HLA‐C*03:04:01:01 by a single nucleotide substitution in exon 4 at codon 236.

ABSTRACT Three novel HLA‐B alleles, HLA‐B*27:297, ‐B*41:97 and ‐B*44:436 , were identified by next‐generation sequencing.

ABSTRACT HLA‐A*02:1040:02 differs from HLA‐A*02:01:01:01 by a single nucleotide substitution in codon 283 (CCC>TCC) in exon 5.

ABSTRACT The novel HLA‐DQB1*02:02:01:28Q shows a point mutation in the intron 3 splice site.

ABSTRACTHLA‐C*06:402 differs from HLA‐C*06:02:01:01 by a nine‐nucleotide (TCCTGGCTG) insertion in exon 5.

Aim Vedolizumab is a humanized monoclonal antibody that binds to α4β7 integrin expressed on most leukocytes and is used for treatment of inflammatory bowel disease. The objective of this study was to assess the effect of recombinant anti-vedolizumab treatment in vitro on allogeneic T and B cell flow cytometry crossmatches (FCXM) in solid organ transplantation. Methods Serum samples from kidney transplant recipients that received parenteral therapeutic vedolizumab monoclonal antibody injection 5 days prior to collection were used in the study. All serum samples were tested for the presence of HLA donor-specific antibodies (DSA) by Luminex single antigen beads assay (Thermo Fisher-One lambda). FCXM were performed using surrogate lymphocytes and sera were treated with heat inactivation (HI, 56°C for 30 mins), dithiothreitol (DTT, 5 mM at 37°C for 15 mins), and inhibitory anti-idiotypic recombinant anti-vedolizumab antibodies (HCA292, Bio-Rad, at 0.1, 0.05, and 0.025 mg/ml at room temperature for 30 min). Results Parenteral administration of therapeutic vedolizumab monoclonal antibodies caused false-positive allogeneic T and B cell FCXM in the absence of HLA DSA. HI and DTT treatment of sera had no effect on the false-positive T and B cell FCXM. However, recombinant anti-vedolizumab antibodies successfully abrogated the false-positive T and B cell FCXM at 0.1 mg/ml and 0.05 mg/ml concentrations (Table 1). Anti-vedolizumab antibodies at 0.1 mg/ml concentration had no effect on the negative and positive crossmatch control serum. Table 1.Serum treatmentFlow cytometry crossmatchT cellB cellHeat inactivationpositivepositiveDTTpositivepositiveAnti-vedoluzimab 0.1mg/mlnegativenegativeAnti-vedoluzimab 0.05mg/mlnegativenegativeAnti-vedoluzimab 0.025mg/mlpositivepositive Conclusions This is the first report showing that therapeutic administration of vedolizumab monoclonal antibodies cause false-positive T and B cell FCXM in absence of HLA DSA, which can preclude from proceeding with allogeneic transplantation. In addition, recombinant anti-vedolizumab antibodies abrogated false-positive allogeneic T and B cell FCXM.

ABSTRACT HLA‐B*38:125 differs from HLA‐B*38:02:01:01 by one nucleotide substitution in codon 248 (GTG>ATG) in exon 4.

ABSTRACT HLA‐DQA1*05:01:21 differs from HLA‐DQA1*05:01:01:02 by one nucleotide substitution in codon 198 (TGC > TGT) in exon 4.

ABSTRACT HLA‐B*07:528 differs from HLA‐B*07:02:01:26 by one nucleotide substitution in codon 286 (GGC>GAC) in exon 5.