Diagnostic and Treatment of Chronic Pathologies Such as Lyme Disease
AssigneesCentre National De La Recherche Scientifique, Institut National de la Sante et de la Recherche Medicale
InventorsHugues Gascan, Marc Michaël Bransten, Sylvie Chevalier, Hans Yssel
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Abstract
The present invention relates to several biomarkers, including IL-1RA, IFN-γ and GM-CSF, whose expressions at the mRNA level and at the protein level, correlate with chronic pathologies, such as Lyme disease, in particular the late chronic form of Lyme disease. More specifically, the invention provides methods and kits for the diagnosis of such chronic pathologies and for the assessment of a patient's response to a treatment, as well as methods and therapeutic agents for the treatment of such chronic pathologies.
Claims20
1-15. (canceled)
An in vitro method for diagnosing a chronic pathology in a subject, said method comprising steps of:
- (a) determining, in a biological sample obtained from said subject, the expression level of interleukin-1 receptor antagonist (IL-1RA);
- and
- (b) comparing the expression level of IL-1RA determined in step (a) with the expression level of IL-1RA determined in a biological sample obtained from a healthy subject or with a predetermined threshold [IL-1RA]0,
- wherein an expression level of IL-1RA determined in step (a) that is higher than the expression level of IL-1RA determined for the healthy subject, or that is higher than the predetermined threshold [IL-1RA]0, is indicative of the chronic pathology, and/or comprising steps of:
- (a′) determining, in a biological sample obtained from said subject, the expression level of interferon-gamma (IFN-γ);
- and
- (b′) comparing the expression level of IFN-γ determined in step (a′) with the expression level of IFN-γ determined in a biological sample obtained from a healthy subject or with a predetermined threshold [IFN-γ]0,
- wherein an expression level of IFN-γ determiner in step (a′) that is lower than the expression level of IFN-γ determined for the healthy subject, or that is lower than the predetermined threshold [IFN-γ]0, is indicative of the chronic pathology,
- and/or comprising steps of:
- (a″) determining, in a biological sample obtained from said subject, the expression level of granulocyte-macrophage colony stimulating factor (GM-CSF);
- and
- (b″) comparing the expression level of GM-CSF determined in step (a″) with the expression level of GM-CSF determined in a biological sample obtained from a healthy subject or with a predetermined threshold [GM-CSF]0,
- wherein an expression level of GM-CSF determiner in step (a″) that is lower than the expression level of GM-CSF determined for the healthy subject, or that is lower than the predetermined threshold [GM-CSF]0, is indicative of the chronic pathology.
An in vitro method for diagnosing a chronic pathology in a subject, said method comprising steps of:
- (a) determining, in a biological sample obtained from said subject, the expression level of IL-1RA and the expression level of IFN-γ;
- and
- (b) calculating the ratio [IL-1RA]/[IFN-γ] between the expression level of IL-1RA and the expression level of IFN-γ determined in step (a);
- and
- (c) comparing the ratio [IL-1RA]/[IFN-γ] calculated in step (b) with the ratio [IL-1RA]/[IFN-γ] determined using a biological sample obtained from a healthy subject or with a predetermined threshold ratio [IL-1RA]/[IFN-γ]0, wherein a ratio [IL-1RA]/[IFN-γ] calculated in step (b) that is higher than the ratio [IL-1RA]/[IFN-γ] determined for the healthy subject, or that is higher than the predetermined threshold ratio [IL-1RA]/[IFN-γ]0, is indicative of the chronic pathology;
- and/or comprising steps of:
- (a′) determining, in a biological sample obtained from said subject, the expression level of IL-1RA and the expression level GM-CSF;
- (b′) calculating the ratio [IL-1RA]/[GM-CSF] between the expression level of IL-1RA and the expression level of GM-CSF determined in step (a′);
- and
- (c′) comparing the ratio [IL-1RA]/[GM-CSF] calculated in step (b′) with the ratio [IL-1RA]/[GM-CSF] determined using a biological sample obtained from a healthy subject or with a predetermined threshold [IL-1RA]/[GM-CSF]0,
- wherein a ratio [IL-1RA]/[GM-CSF] calculated in step (b′) that is higher than the ratio [IL-1RA]/[GM-CSF] determined for a healthy subject, or that is higher than the predetermined threshold ratio [IL-1RA]/[GM-CSF]0, is indicative of the chronic pathology.
A kit for the in vitro diagnosis of a chronic disease, said kit comprising a reagent that specifically reacts with IL-1RA mRNA or protein, or with IFN-γ mRNA or protein, or with GM-CSF mRNA or protein.
A method for treating a chronic pathology in a subject comprising a step of administering, to the subject, a therapeutically effective amount of a therapeutic agent or a pharmaceutical composition thereof, wherein said therapeutic agent is selected from the group consisting of IL-1RA therapeutic agents, TLR10 therapeutic agents, GM-CSF, INF-γ and IL-2.
Dependencies are inferred from the claim text.