Screening Methods for Transfusion Related Acute Lung Injury
AssigneesDrk Blutspendienst West GmbH, Ernst-Moritz-Arndt-Universitat Greifswald
InventorsANDREAS GREINACHER, JAN WESCHE, JUERGEN BUX, ANGELIKA REIL
Life of this patent
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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.
Claims43
1-16. (canceled)
A method of determining whether a donor tissue intended for transplant or transfusion is likely to be rejected in a human recipient wherein the human recipient expresses HNA-3a specific antibodies, comprising
- a) obtaining a sample of the tissue intended for transplant or transfusion,
- b) extracting nucleic acids from the sample,
- c) contacting the nucleic acids with oligonucleotide probes that hybridize to a fragment of SEQ ID NO:
- 3, and
- d) detecting hybridization of the probe to the nucleic acids, wherein hybridization of the probe indicates the presence of an HNA-3a nucleic acid and the presence of HNA-3a nucleic acid in the sample indicates that the sample is likely to be rejected in a human recipient that expresses HNA-3a specific antibodies.
A method of determining whether a donor tissue intended for transplant or transfusion is likely to be rejected in a human recipient wherein the human recipient expresses HNA-3b specific antibodies, comprising
- a) obtaining a sample of the tissue intended for transplant or transfusion,
- b) extracting nucleic acids from the sample,
- c) contacting the nucleic acids with oligonucleotide probes that hybridize to a fragment of SEQ ID NO:
- 4, and
- d) detecting hybridization of the probe to the nucleic acids, wherein hybridization of the probe indicates the presence of an HNA-3b nucleic acid and the presence of HNA-3b nucleic acid in the sample indicates that the sample is likely to be rejected in a human recipient that expresses HNA-3b specific antibodies.
A method of determining the susceptibility of a human transplant or transfusion recipient for developing transfusion related acute lung injury (TRALI) or graft versus host disease (GVHD), wherein the donor tissue contains HNA-3a specific antibodies, comprising
- a) obtaining a biological sample from the human transplant or transfusion recipient prior to transplantation or transfusion,
- b) extracting nucleic acids from the biological sample,
- c) contacting the nucleic acids with a oligonucleotide probe that hybridizes to a fragment of the nucleotide sequence of SEQ ID NO:
- 1, and
- d) detecting hybridization of the probe to the nucleic acid, wherein hybridization of the probe to the nucleic acids indicates the presence of HNA-3a nucleic acid in the biological sample and the presence of HNA-3a in the biological sample indicates that a human transfusion or transplant recipient is susceptible for developing TRALI or GVHD.
A method of determining the susceptibility of a human transplant or transfusion recipient for developing transfusion related acute lung injury (TRALI) or graft versus host disease (GVHD), wherein the donor tissue contains HNA-3b specific antibodies, comprising
- a) obtaining a biological sample from the human transplant or transfusion recipient prior to transplantation or transfusion,
- b) extracting nucleic acids from the biological sample,
- c) contacting the nucleic acids with a oligonucleotide probe that hybridizes to a fragment of the nucleotide sequence of SEQ ID NO:
- 2, and
- d) detecting hybridization of the probe to the nucleic acid, wherein hybridization of the probe to the nucleic acids indicates the presence of HNA-3b nucleic acid in the biological sample and the presence of HNA-3b in the biological sample indicates that a human transfusion or transplant recipient is susceptible for developing TRALI or GVHD.
29-31. (canceled)
A method of determining whether a donor tissue intended for transplant or transfusion is likely to be rejected in a human recipient wherein the human recipient has HNA-3a specific antibodies, comprising
- a) obtaining a sample from the tissue,
- b) extracting nucleic acids from the sample,
- c) amplifying 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
- c) detecting the fragment of HNA-3a nucleic acid in the sample, wherein the presence of HNA-3a nucleic acid in the sample indicates that the sample is likely to be rejected in a human recipient that has HNA-3a specific antibodies.
A method of determining whether a donor tissue intended for transplant or transfusion is likely to be rejected in a human recipient wherein the human recipient has HNA-3b specific antibodies, comprising
- a) obtaining a sample from the tissue,
- b) extracting nucleic acids from the sample,
- c) amplifying a fragment of HNA-3b nucleic acid of SEQ ID NO:
- 4 from the extracted nucleic acids using at least one oligonucleotide primer specific for HNA-3b nucleic acid, and
- c) detecting the fragment of HNA-3b nucleic acid in the sample, wherein the presence of HNA-3b nucleic acid in the sample indicates that the sample is likely to be rejected in a human recipient that has HNA-3b specific antibodies.
A method of determining the susceptibility of a human transplant or transfusion recipient for developing transfusion related acute lung injury (TRALI) or graft versus host disease (GVHD), wherein the donor tissue contains HNA-3a specific antibodies, comprising
- a) obtaining a biological sample from the human transplant or transfusion recipient prior to transplantation or transfusion,
- b) extracting nucleic acids from the biological sample,
- c) amplifying a fragment of the HNA-3a nucleic acid (SEQ ID NO:
- 3) from the extracted nucleic acids using at least one oligonucleotide primers specific for HNA-3a nucleic acid in the biological sample, and
- d) detecting the presence of HNA-3a nucleic acid in the biological sample, wherein the presence of HNA-3a nucleic acid in the biological sample indicates that the human transfusion or transplant recipient is susceptible for developing TRALI or GVHD.
A method of determining the susceptibility of a human transplant or transfusion recipient for developing transfusion related acute lung injury (TRALI) or graft versus host disease (GVHD), wherein the donor tissue contains anti-HNA-3b antibodies, comprising
- a) obtaining a biological sample from the human transplant or transfusion recipient prior to transplantation or transfusion,
- b) extracting nucleic acids from the biological sample,
- c) amplifying a fragment of the HNA-3b nucleic acid (SEQ ID NO:
- 4) from the extracted nucleic acids using at least one oligonucleotide primer specific for HNA-3b nucleic acid, and
- d) detecting the presence of HNA-3b nucleic acid in the biological sample, wherein the presence of HNA-3b nucleic acid in the biological sample indicates that the human transfusion or transplant recipient is susceptible for developing TRALI or GVHD.
42-64. (canceled)
A kit comprising
- a) an oligonucleotide probe that hybridizes to a fragment of the nucleic acid sequence of SEQ ID NO:
- 3, and
- b) one or more oligonucleotide probes that hybridizes to a fragment of a nucleic acid sequence selected from the group consisting of SEQ ID NO:
- 5, SEQ ID NO:
- 7, SEQ ID NO:
- 9, SEQ ID NO:
- 11 and an HLA nucleotide sequence.
A kit comprising
- a) an oligonucleotide probe that hybridizes to a fragment of the nucleic acid sequence of SEQ ID NO:
- 4, and
- c) one or more oligonucleotide probes that hybridize to a fragment of a nucleic acid sequence selected from the group consisting of SEQ ID NO:
- 5, SEQ ID NO:
- 7, SEQ ID NO:
- 9, SEQ ID NO:
- 11 and an HLA nucleotide sequence.
71-72. (canceled)
A kit comprising
- a) one or more oligonucleotide primers for amplifying a fragment of the HNA-3a nucleic acid of SEQ ID NO:
- 3, and
- c) one or more oligonucleotide primers for amplifying a fragment of a nucleic acid sequence selected from the group consisting of SEQ ID NO:
- 5, SEQ ID NO:
- 7, SEQ ID NO:
- 9, SEQ ID NO:
- 11 and an HLA nucleotide sequence.
A kit comprising
- a) one or more oligonucleotide primers for amplifying a fragment of the HNA-3b nucleic acid of SEQ ID NO:
- 4, and
- b) one or more oligonucleotide primers for amplifying a fragment of a nucleic acid sequence selected from the group consisting of SEQ ID NO:
- 5, SEQ ID NO:
- 7, SEQ ID NO:
- 9, SEQ ID NO:
- 11 and an HLA nucleotide sequence.
76-94. (canceled)
A method of screening for HNA-3b genotype in a human subject comprising
- a) obtaining a biological sample from the human subject,
- b) extracting nucleic acids from the biological sample, and
- b) detecting a fragment of a nucleic acid sequence of SEQ ID NO:
- 4 in the biological sample, wherein the fragment comprises codon 154 of SEQ ID NO:
- 4,
- wherein the detection of codon 154 of SEQ ID NO:
- 4 indicates that the human subject has the HNA-3b genotype.
99-107. (canceled)
A method of screening for HNA-3a genotype in a human subject comprising
- a) obtaining a biological sample from the human subject,
- b) extracting nucleic acids from the biological sample, and
- b) detecting a fragment of a nucleic acid sequence of SEQ ID NO:
- 3 in the biological sample, wherein the fragment comprises codon 154 of SEQ ID NO:
- 3,
- wherein the detection of codon 154 encoding the amino acid arginine indicates that the human subject has the HNA-3a genotype.
A method of determining the HNA-3 genotype in a human subject comprising
- a) obtaining a biological sample from the human subject,
- b) extracting nucleic acids from the biological sample, and
- b) detecting a fragment of a nucleic acid sequence of SEQ ID NO:
- 3 or SEQ ID NO:
- 4 in the biological sample, wherein the fragment comprises codon 154 of SEQ ID NO:
- 3 or SEQ ID NO:
- 4,
- wherein the detection of codon 154 encoding the amino acid arginine indicates that the human subject has the HNA-3a genotype and detection of codon 154 encoding amino acid glutamine indicates the human subject has the HNA-3b genotype.
Dependencies are inferred from the claim text.