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-8999651-B2
Publication Date
2015-04-07
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 disclosure identifies transfusion related acute lung injury (TRALI)-relevant human neutrophil antigen HNA-3a and HNA-3b as CTL2 (SLC44A2) variants differentiated by the SNP rs2288904, with codon 154 having Arg in HNA-3a and Gln in HNA-3b.
The disclosure provides a method to detect anti-HNA-3b antibodies in a human blood, plasma or serum sample by contacting the sample with a bead-bound polypeptide comprising the amino acid sequence of SEQ ID NO: 2 or an antigenic fragment thereof and contacting the sample with an antibody having specific reactivity to a human antibody that is detectably labeled. Detecting the presence or absence of a complex is used to indicate the presence of anti-HNA-3b antibodies likely to induce TRALI or GVHD in the sample.
The disclosure further defines antigenic fragments of the HNA-3b polypeptide using specified SEQ ID NOs and describes optionally expanding the antigen panel to include additional polypeptides and corresponding antibodies. Such additional antigens include Fc-γ receptor Mb, CD177, CD11b/CD11a, and HLA, with complex detection indicating likelihood for TRALI or GVHD.
Claims Coverage
The document contains one independent claim directed to an immunoassay-style method using a bead-bound HNA-3b polypeptide, a detectably labeled anti-human antibody, and detecting complex formation to indicate anti-HNA-3b antibodies likely to induce TRALI or GVHD. Dependent claims further narrow fragment sequences, sample source, and detectable label, and optionally expand to additional antigens and antibody specificities for complex detection.
Bead-bound HNA-3b polypeptide complex detection for TRALI or GVHD indication
Contacting a human blood, plasma or serum sample with a polypeptide comprising the amino acid sequence of SEQ ID NO: 2 or an antigenic fragment thereof, wherein the polypeptide is bound to a bead; contacting the sample with an antibody with specific reactivity to a human antibody, wherein the anti-human antibody is detectably labeled; detecting the presence or absence of a complex, wherein the presence of the complex indicates the presence of anti-HNA-3b antibodies likely to induce TRALI or GVHD in the sample.
Specified HNA-3b antigenic fragment sequences
The method characterized in that the antigenic fragment includes an amino acid sequence selected from SEQ ID NO: 19, 20, 21, 22, 23, 24, and 26.
Recipient-derived sample prior to transplant or transfusion
The method wherein the sample is obtained from a human transplant or transfusion recipient before transplantation or transfusion.
Additional antigen panel complexes to indicate likelihood of TRALI or GVHD
The method further includes contacting a biological sample with Fc-γ receptor Mb, CD177, CD11b, CD11a, or an HLA antigen or antigenic fragments to form complexes with corresponding specific antibodies, and then detecting the complexes to indicate a likelihood for TRALI or GVHD.
Donor-derived sample
The method of claim 1 is performed using a sample obtained from a human transplant or transfusion donor.
Fluorescent detectably labeled anti-human antibody
The method of claim 1 is characterized in that the detectable label is a fluorescent label.
Overall, the claim coverage centers on detecting complexes formed with a bead-bound HNA-3b polypeptide using a detectably labeled anti-human antibody, where complex presence indicates anti-HNA-3b antibodies likely to induce TRALI or GVHD. Dependent features define allowable antigenic fragments, restrict sample source to donor or recipient timing, specify a fluorescent label, and expand complex detection to additional antigens for likelihood indication.
Stated Advantages
Detecting the presence of anti-HNA-3b antibodies likely to induce TRALI or GVHD in the sample.
Documented Applications
Screening of a human blood, plasma or serum sample for anti-HNA-3b antibodies likely to induce TRALI or GVHD, including use with a recipient sample obtained before transplantation or transfusion, and use with a donor-derived sample.
Expanded detection using additional antigenic polypeptides, including Fc-γ receptor Mb, CD177, CD11b, CD11a, and HLA, to indicate a likelihood for TRALI or GVHD based on presence of corresponding antibody complexes.
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