Screening methods for transfusion related acute lung injury
Inventors
Greinacher, Andreas • Wesche, Jan • Bux, Juergen • Reil, Angelika
Assignees
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Publication Number
US-8435733-B2
Publication Date
2013-05-07
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 identifies neutrophil antigen HNA-3a and HNA-3b as allelic variants of CTL2 (SLC44A2), defined by a key SNP (rs2288904) that causes an Arg154 substitution in HNA-3a and a Gln154 substitution in HNA-3b. It relates these allelic forms to human recipient antibodies specific for the amino acid sequences and antigenic fragments of SEQ ID NO: 1, and provides nucleic acid and protein sequences for HNA-3a and HNA-3b using SEQ ID NO: 1 through SEQ ID NO: 4.
The invention addresses the problem of determining whether donor tissue intended for transplant or transfusion is likely to be rejected in a human recipient that expresses antibodies specific for HNA-3a. It provides methods that obtain a donor tissue sample, extract nucleic acids, and test for the presence of HNA-3a nucleic acid corresponding to nucleotide sequences encoding the amino acid sequence of SEQ ID NO: 1 or an antigenic fragment thereof.
Hybridization-based detection is disclosed using oligonucleotide probes that hybridize to a fragment of SEQ ID NO: 3, where detected hybridization indicates presence of HNA-3a nucleic acid associated with likely rejection. Amplification-based detection is also provided in which a fragment of HNA-3a nucleic acid of SEQ ID NO: 3 is amplified using at least one oligonucleotide primer specific for HNA-3a nucleic acid, followed by detection of the amplified fragment.
Claims Coverage
The partial content provides two independent claims. Across these claims, the coverage centers on determining likely rejection of donor tissue in a human recipient by detecting the presence of HNA-3a nucleic acid using either oligonucleotide probe hybridization or oligonucleotide primer-driven amplification.
Detecting HNA-3a nucleic acid with oligonucleotide probe hybridization to indicate likely rejection
Obtain a sample of tissue intended for transplant or transfusion, extract nucleic acids, contact the nucleic acids with oligonucleotide probes that hybridize to a fragment of SEQ ID NO: 3, and detect hybridization; hybridization indicates the presence of an HNA-3a nucleic acid comprising the nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 1 or an antigenic fragment thereof, wherein presence indicates the sample is likely to be rejected in a human recipient that expresses HNA-3a-specific antibodies.
Amplifying and detecting HNA-3a nucleic acid fragments with HNA-3a-specific primers to indicate likely rejection
Obtain a sample from tissue intended for transplant or transfusion, extract nucleic acids, amplify a fragment of HNA-3a nucleic acid of SEQ ID NO: 3 from the extracted nucleic acids using at least one oligonucleotide primer specific for HNA-3a nucleic acid, and detect the amplified fragment; wherein presence of HNA-3a nucleic acid indicates the sample is likely to be rejected in a human recipient that has HNA-3a specific antibodies.
The independent claims define a nucleic-acid-based rejection likelihood determination anchored to HNA-3a in donor tissue. The core inventive distinction is whether HNA-3a nucleic acid is identified by probe hybridization to a SEQ ID NO: 3 fragment or by primer-driven amplification followed by detection.
Stated Advantages
Indicates whether a donor tissue intended for transplant or transfusion is likely to be rejected in a human recipient expressing HNA-3a specific antibodies.
Documented Applications
Screening donor tissues intended for transplant or transfusion to determine likely rejection in a human recipient.
TRALI/GVHD-risk-focused screening and genotyping of donor tissues/recipients using antibody-based assays, aptamer-based detection, and nucleic-acid hybridization or PCR amplification concepts.
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