Compositions and methods relating to lyme disease

Patent metadata

Field	Value
Publication number	US-9383360-B2
Application number	US-201314372171-A
Country	US
Kind code	B2
Filing date	Jan 21, 2013
Priority date	Jan 20, 2012
Publication date	Jul 5, 2016
Grant date	Jul 5, 2016

Abstract

Compositions and methods of the present invention relating to B. burgdorferi HtrA sensu lato (BbHtrA) protease activity, its substrates, cleavage products, biological effects and use in detection, diagnosis and/or treatment of Lyme disease are provided.

First claim

The invention claimed is:

1. A method of aiding in the diagnosis of Lyme disease, comprising: assaying a first sample obtained from a subject having, or suspected of having, Lyme disease for one or more peptides selected from the group consisting of: peptides of SEQ ID NOs: 56, 59, 60, 61, 62, 63, 64, 66 and the product of cleavage at cleavage sites 108 and 124, produced by proteolytic activity of Borrelia burgdorferi sensu lato HtrA on at least one host protein substrate, to produce an assay result wherein detection of the one or more peptides is indicative of an active Borrelia burgdorferi sensu lato infection in the subject.

2. The method of claim 1 , further comprising:
assaying a second sample obtained from the subject having, or suspected of having, Lyme disease to detect at least one inflammatory cytokine or chemokine selected from: CXCL1, CCL1, sICAM-1, IL-6, IL-8, CCL2, and CCL5, wherein detection of the one or more peptides in combination with an increase in CXCL1, CCL1, sICAM-1, IL-6, IL-8, CCL2, and CCL5 compared to a standard is indicative of an active Borrelia burgdorferi sensu lato infection in the subject.

3. The method of claim 1 , further comprising: assaying a further sample obtained from a subject having, or suspected of having, Lyme disease for one or more of the peptides.

4. The method of claim 1 , wherein the first sample is selected from: whole blood, plasma, serum, urine, cerebrospinal fluid, synovial fluid and/or a biopsy sample, wherein the biopsy sample is skin or joint tissue.

5. The method of claim 2 , wherein the second sample is selected from: whole blood, plasma, serum, urine, cerebrospinal fluid, synovial fluid and/or a biopsy sample, wherein the biopsy sample is skin or joint tissue.

6. The method of claim 1 , wherein detecting the one or more peptides produced by proteolytic activity of Borrelia burgdorferi sensu lato HtrA on at least one host protein substrate comprises an immunoassay and/or mass spectrometry.

7. A commercial package for aiding in the diagnosis of Lyme disease in a subject comprising:
a reagent selected from the group consisting of: one or more peptides selected from the group consisting of: peptides of SEQ ID NOs: 56, 59, 60, 61, 62, 63, 64, 66 and the product of cleavage at cleavage sites 108 and 124, containing a neoepitope produced by proteolytic activity of Borrelia burgdorferi sensu lato HtrA on a host substrate; and one or more substrates for Borrelia burgdorferi sensu lato HtrA protease.

8. The commercial package of claim 7 , wherein the one or more substrates is selected from the group consisting of: one or more substrates for Borrelia burgdorferi sensu lato HtrA protease selected from the group consisting of: aggrecan, fibronectin, biglycan, cartilage oligomeric matrix protein (COMP).

9. The commercial package of claim 7 wherein the one or more peptides are arrayed on a support.

10. The method of claim 3 , wherein the further sample is selected from: whole blood, plasma, serum, urine, cerebrospinal fluid, synovial fluid and/or a biopsy sample, wherein the biopsy sample is skin or joint tissue.

Assignees

• Us Health

Inventors

• Russell Theresa M
• Johnson Barbara J B

Classifications

• G01N2469/10

  Detection of antigens from microorganism in sample from host · CPC title

• G01N2469/20

  Detection of antibodies in sample from host which are directed against antigens from microorganisms · CPC title

• G01N2800/26

  Infectious diseases, e.g. generalised sepsis · CPC title

• G01N2333/952

  derived from bacteria · CPC title

• G01N33/581

  with enzyme label (including co-enzymes, co-factors, enzyme inhibitors or substrates) · CPC title