Screening methods for transfusion related acute lung injury (TRALI)
Inventors
Greinacher, Andreas • Wesche, Jan • Bux, Juergen • Reil, Angelika
Assignees
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Publication Number
US-9963741-B2
Publication Date
2018-05-08
Expiration Date
Abstract
The invention relates to the discovery that HNA-3a and HNA-3b are antigens within a polypeptide sequence that is highly similar to the CTL2 amino acid sequence. This invention provides methods and kits for screening for HNA-3a and HNA-3b specific antibodies, HNA-3a and HNA-3b polypeptides and HNA-3a and HNA-3b nucleic acids in a sample of a biological tissue intended for transplantation.
Core Innovation
The invention relates to transfusion related acute lung injury (TRALI) immunogenetics by identifying human platelet alloantigen (HNA) antigens and using HNA-3b nucleic acid as a genetic indicator in transplant or transfusion-related biological samples. The document identifies HNA-3b as a CTL2 (SLC44A2) variant with a single nucleotide polymorphism (SNP), rs2288904, that changes an amino acid at codon 154 (R in HNA-3a versus Q in HNA-3b).
The disclosed approach centers on detecting HNA-3b nucleic acid fragments in blood, plasma, or serum to determine recipient susceptibility or risk in transplant or transfusion settings. The presence of HNA-3b nucleic acid indicates adverse outcomes in recipients with HNA-3b antibodies.
In addition to HNA-3b, the document describes embodiments using antigenic nucleic acid targets from other HNA types and an HLA antigen nucleic acid, including HNA-1, HNA-2, HNA-4, and HNA-5, as part of multi-antigen panel logic for rejection, TRALI, and GVHD indications.
Claims Coverage
Two independent methods are described. Across the independent claims, there are 2 core inventive features centered on amplifying and detecting an HNA-3b nucleic acid fragment and detecting an HNA-3b nucleic acid fragment using HNA-3b-specific oligonucleotide probes, each tied to rejection, TRALI, and GVHD indications in recipients having corresponding antibodies.
Amplifying HNA-3b nucleic acid fragment and detecting for adverse-outcome indication
A method comprising amplifying a fragment of HNA-3b nucleic acid from blood, plasma, or serum using at least one oligonucleotide primer that amplifies a nucleotide sequence encoding amino acid sequences selected from SEQ ID NOs 19, 20, 21, 22, 23, 24, and 26, and detecting the presence of the HNA-3b nucleic acid in the blood, plasma, or serum to indicate that the human transfusion or transplant recipient is likely to be rejected, induce TRALI, or induce GVHD in a human recipient that has HNA-3b antibodies.
Detecting HNA-3b nucleic acid fragment using HNA-3b-specific probes and adverse-outcome indication
A method comprising detecting a fragment of HNA-3b nucleic acid in a blood, plasma, or serum sample using at least one oligonucleotide probe specific for HNA-3b nucleic acid, wherein the oligonucleotide probe comprises a nucleotide sequence that hybridizes to a nucleic acid sequence that encodes an amino acid sequence selected from SEQ ID NOs 19, 20, 21, 22, 23, 24, and 26, and detecting the presence of the HNA-3b nucleic acid in the blood, plasma, or serum to indicate that the human transfusion or transplant recipient is likely to be rejected, induce TRALI, or induce GVHD in a human recipient that has HNA-3b antibodies.
The claims coverage is directed to nucleic-acid-based detection of HNA-3b in blood, plasma, or serum, either by amplification with specified primer targets or by probe hybridization with HNA-3b-specific oligonucleotide probes, where detection is used to indicate likely rejection, TRALI, or GVHD in recipients with HNA-3b antibodies.
Stated Advantages
Indicates that a human transfusion or transplant recipient is likely to be rejected when HNA-3b nucleic acid is detected.
Indicates that a human transfusion or transplant recipient is likely to induce TRALI when HNA-3b nucleic acid is detected.
Indicates that a human transfusion or transplant recipient is likely to induce GVHD when HNA-3b nucleic acid is detected.
Documented Applications
Assessing likely rejection, TRALI, and/or GVHD risk in a human recipient associated with transfusion or transplant using detection of HNA-3b nucleic acid from blood, plasma, or serum samples.
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