Anellovirus genome quantification as a biomarker of immune suppression
AssigneesInstitut Pasteur, Université Paris Cité, Assistance Publique-Hopitaux de Paris, Pathoquest, Ecole Nationale Veterinaire D' Alfort
InventorsMarc ELOIT, Justine CHEVAL, Charles HEBERT, Marc LECUIT
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Abstract
The present invention relates to the use of the measure of anelloviral load for the determination of immunosuppression. More precisely, the present invention provides a method for characterizing the immunosuppressed or non-immunosuppressed status of a subject, comprising the steps of determining the anelloviral load from a biological sample of the said subject, and determining from the said comparison the immunosuppressed or non-immunosuppressed status. The determination of the immunosuppressed status of the subject can then be used to design or adapt a therapeutic treatment.
Claims18
A method, comprising:
- 1) obtaining a biological sample from a human subject who is or is suspected of being immunosuppressed;
- and
- 2) measuring the number of anellovirus DNA sequences in the sample by a method comprising detecting Torque teno virus (TTV) DNA, Torque teno midi virus (TTMDV) DNA, and Torque teno mini virus (TTMV) DNA, wherein measuring the number of anellovirus DNA sequences in the sample comprises at least one amplification step or sequencing step with a primer comprising at least 12 consecutive bases of SEQ ID NO:
- 4, which hybridizes specifically to TTV, TTMDV, and TTMV DNA within position +121 to +151 relative to the TATA box consensus or at least 12 consecutive bases of SEQ ID NO:
- 5, which hybridizes specifically to TTV, TTMDV, and TTMV DNA within position +20 to +53 relative to the TATA box consensus, with the proviso that the primer does not have the sequence of SEQ ID No. 6 or SEQ ID No. 7, using a nucleic acid amplification instrument and/or a sequencing instrument;
- 3) measuring the number of total DNA sequences in the sample, wherein measuring the number of total DNA sequences in the sample comprises using a nucleic acid amplification instrument and/or a sequencing instrument;
- and
- 4) generating a ratio of the measured number of anellovirus DNA sequences in the sample to the measured number of total DNA sequences in the sample, wherein the ratio of the measured number of anellovirus DNA sequences in the sample to the measured number of total DNA sequences in the sample is higher than 0.2×10−4 in the sample;
- responsive to measuring the ratio at higher than 0.2×10−4, determining that the human subject is immunosuppressed.
A method of preparing a value indicative of an immunosuppressed status in a human subject who is or is suspected of being immunosuppressed, comprising:
- 1) obtaining a biological sample from the human subject;
- 2) using a nucleic acid amplification instrument and/or a sequencing instrument with a primer comprising at least 15 consecutive bases of SEQ ID NO:
- 4 or SEQ ID NO:
- 5, with the proviso that the primer does not have the sequence of SEQ ID No. 6 or SEQ ID No. 7 to measure the number of anellovirus DNA sequences in the sample by detecting Torque teno virus (TTV) DNA, Torque teno midi virus (TTMDV) DNA, and Torque teno mini virus (TTMV) DNA in the sample to generate a combined value of the measured number of anellovirus;
- and
- 3) using a nucleic acid amplification instrument and/or a sequencing instrument to measure the number of total DNA sequences in the sample;
- 4) generating the value by determining a ratio of the measured number of anellovirus DNA sequences to the measured number of total DNA sequences in the sample,
- wherein if the value is higher than 0.2×10−4 in the sample, the human subject is immunosuppressed.
Dependencies are inferred from the claim text.