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-8084216-B2
Publication Date
2011-12-27
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 disclosure identifies TRALI-associated HNA-3 antigens as CTL2-derived polypeptides, specifically HNA-3a and HNA-3b, where the antigens differ by a SNP rs2288904 at codon 154 (Arg vs Gln). The document describes antigenic fragments of these polypeptides and provides sequence-defined targets associated with SEQ ID NO: 1 (HNA-3a) and SEQ ID NO: 2 (HNA-3b), including enumerated antigenic fragments referenced by SEQ ID NOs.
The disclosure provides methods in which a donor tissue intended for transplant or transfusion is assessed for likelihood to induce TRALI or GVHD in a human recipient that expresses the HNA-3a antigen. The method includes obtaining a donor sample, contacting the sample with a polypeptide comprising the amino acid sequence of SEQ ID NO: 1 or an antigenic fragment thereof to form a complex with HNA-3a specific antibodies, and detecting the complex, where presence of the complex indicates that the donor tissue is likely to induce TRALI or GVHD.
The disclosure further provides methods for determining susceptibility of a human transplant or transfusion recipient to rejecting transplanted or transfused tissue by detecting complexes formed between polypeptides comprising the amino acid sequence of SEQ ID NO: 1 or an antigenic fragment thereof and HNA-3a specific antibodies in a recipient sample. The document additionally expands the antigen targets beyond HNA-3a by including other HNA antigens, such as HNA-1, HNA-2, HNA-4, and HNA-5, and an HLA antigen, with corresponding antibody complexes detected to indicate likelihood or susceptibility.
Claims Coverage
The partial content includes two independent methods. Both independent claims rely on forming and detecting antigen-antibody complexes using CTL2-derived HNA-3a polypeptides (SEQ ID NO: 1) or antigenic fragments, and both treat the presence of detected complexes as an indicator for a clinical likelihood or susceptibility.
Donor likelihood assay using HNA-3a polypeptide complex detection
Obtaining a sample from the donor of tissue intended for transplant or transfusion in a human subject; contacting the sample with a polypeptide comprising the amino acid sequence of SEQ ID NO: 1 or an antigenic fragment thereof to form a complex with HNA-3a specific antibodies in the sample; detecting the complex, wherein the presence of the complex indicates that the donor tissue is likely to induce transfusion related acute lung injury (TRALI) or graft versus host disease (GVHD) in a human recipient that expresses the HNA-3a antigen.
Recipient susceptibility assay using HNA-3a polypeptide complex detection
Obtaining a biological sample from the human transplant or transfusion recipient prior to transplantation or transfusion; contacting the biological sample with polypeptide comprising the amino acid sequence of SEQ ID NO: 1 or an antigenic fragment thereof to form a complex with HNA-3a specific antibodies in the biological sample; detecting the complex, wherein the presence of the complex in the biological sample indicates that the human transplant or transfusion recipient is susceptible for rejecting the transplanted or transfused tissue.
Across the two independent claims, the core coverage is directed to detecting complexes formed between HNA-3a specific antibodies and CTL2-derived HNA-3a polypeptides (SEQ ID NO: 1) or enumerated antigenic fragments, where such detection is used to indicate either donor-induced likelihood of TRALI/GVHD or recipient susceptibility to rejection.
Stated Advantages
Indicates whether donor tissue intended for transplant or transfusion is likely to induce TRALI or GVHD in a recipient expressing the HNA-3a antigen.
Indicates whether a transplant or transfusion recipient is susceptible for rejecting transplanted or transfused tissue.
Documented Applications
Determining whether donor tissue intended for transplant or transfusion will induce TRALI or GVHD in a human recipient expressing the HNA-3a antigen.
Determining susceptibility of a transplant or transfusion recipient for rejecting transplanted or transfused tissue prior to transplantation or transfusion.
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