Method of diagnosing and treating Epstein Barr virus-based myalgic encephalomyelitis chronic fatigue syndrome patients

• US 10,215,755 B2
• Filed: 10/29/2015
• Issued: 02/26/2019
• Est. Priority Date: 10/04/2012
• Status: Active Grant

• Current Assignee: CFS, LLC, Ohio State University
• Original Assignee: CFS, LLC, Ohio State University
• Inventors: Lerner, A. Martin, Glaser, Ronald M.
• Primary Examiner(s): Boesen, Agnieszka
• Application Number:
  US14/926,989
• Publication Number:
  US 20170146534A1
• Time in Patent Office: 1,216 Days
• Field of Search: None
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/662 Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
• CPC Class Codes: A61K 31/7056 containing five-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: G01N 2333/05 Epstein-Barr virus
• CPC Class Codes: G01N 33/56994 Herpetoviridae, e.g. cytomegalovirus, Epstein-Barr virus
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

A method of diagnosing a subset of Epstein Barr Virus, Myalgic Encephalomyelitis Chronic Fatigue Syndrome (ME/CFS) patients through a multi-prong clinical/serological analysis is provided wherein Epstein Barr Virus Abortive Lytic Replication (EBV) is determined as the specific causal agent through the use of serum antibodies to EBV encoded dUTPase and serum antibodies to EBV DNA Polymerase as molecular markers. A method of treating patients diagnosed with Epstein Barr Virus Abortive Lytic Replication (EBV), Myalgic Encephalomyelitis Chronic Fatigue Syndrome (ME/CFS) with specific antiviral nucleosides is also provided, to alleviate the condition.

Claims

1. A method of identifying a Epstein-Barr virus (EBV) subset of Myalgic Encephalomyelitis-Chronic Fatigue Syndrome patients, the method comprising the step of:

incubating EBV Early Antigen, Diffuse and at least one of EBV encoded DNA polymerase or EBV encoded dUTPase with a sample from a Myalgic Encephalomyelitis-Chronic Fatigue Syndrome patient, where the EBV Early Antigen, Diffuse are covalently coupled to microspheres and the at least one of EBV encoded DNA polymerase or EBV encoded dUTPase are covalently coupled to microspheres that are different from the EBV Early Antigen, Diffuse coupled microspheres;

detecting binding of serum antibodies from the sample to the EBV Early Antigen, Diffuse and the at least one of EBV encoded DNA polymerase or EBV encoded dUTPase; and

identifying the patient with Epstein Barr Abortive Lytic Replication when binding of the serum antibodies to the EBV Early Antigen, Diffuse and the at least one of EBV encoded DNA polymerase or EBV encoded dUTPase is detected.

2. The method of claim 1, further comprising the steps of determining an Energy Index Point Score value of the patient and obtaining the sample from the patient when the Energy Index Point Score value is 5 or less.

3. The method of claim 2, wherein the incubating step includes incubating EBV Early Antigen, Diffuse, EBV encoded DNA polymerase, and EBV encoded dUTPase with the sample, where the EBV encoded DNA polymerase are covalently coupled to microspheres that are different from the EBV Early Antigen Diffuse coupled microspheres and the EBV encoded dUTPase are covalently coupled to microspheres that are different from the EBV encoded DNA polymerase coupled microspheres and the EBV Early Antigen Diffuse coupled microspheres;

the detecting step includes detecting binding of serum antibodies to the EBV Early Antigen Diffuse, the EBV encoded DNA polymerase, and the EBV encoded dUTPase; and

the identifying step includes identifying the patient with Epstein Barr Abortive Lytic Replication when binding of the serum antibodies to the EBV Early Antigen Diffuse, the EBV encoded DNA polymerase, and the EBV encoded dUTPase is detected.

4. The method of claim 1, wherein the patient has an Energy Index Point Score value of 5 or less.

5. The method of claim 1, wherein the EBV Early Antigen, Diffuse coupled microspheres have a color that is different from a color of the at least one of the EBV encoded DNA polymerase or the EBV encoded dUTPase coupled microspheres.

6. The method of claim 3, wherein the EBV Early Antigen, Diffuse coupled microspheres, the EBV encoded DNA polymerase coupled microspheres, and the EBV encoded dUTPase coupled microspheres each have a color that is different from the other microspheres.

7. The method of claim 1 further comprising testing the patient for abnormal cardiac functionality, where the identifying step includes identifying the patient with Epstein Barr Abortive Lytic Replication when the patient has abnormal cardiac functionality.

8. The method of claim 1, wherein the identifying step includes identifying the patient with Epstein Barr Abortive Lytic Replication when binding of the serum antibodies to the EBV Early Antigen, Diffuse is detected at an antibody titer of 20 or more.

9. The method of claim 1, wherein the incubating step includes incubating EBV structural antigen with the sample, where the EBV structural antigen are covalently counted to microspheres that are different from the EBV Early Antigen, Diffuse coupled microspheres and the at least one of EBV encoded DNA polymerase or EBV encoded dUTPase coupled microspheres;

the detecting step includes detecting binding of IgM antibodies from the sample to the EBV structural antigen; and

the identifying step includes identifying the patient with Epstein Barr Abortive Lytic Replication when binding of the IgM antibodies to the EBV structural antigen is detected at an antibody titer of less than 20.

10. The method of claim 9, wherein the EBV structural antigen is at least one of EBV viral capsid antigen (VCA) or EBV VCA p18 peptide.

11. The method of claim 3, wherein the incubating step includes incubating EBV structural antigen with the sample, where the EBV structural antigen are covalently coupled microspheres that are different from the EBV Early Antigen, Diffuse coupled microspheres, the EBV encoded DNA polymerase coupled microspheres, and the EBV encoded dUTPase coupled microspheres;

the detecting step includes detecting binding of IgM antibodies from the sample to the EBV structural antigen; and

the identifying step includes identifying the patient with Epstein Barr Abortive Lytic Replication when binding of the IgM antibodies to the EBV structural antigen is detected at an, antibody titer of less than 20.

12. The method of claim 1, wherein the serum antibodies are IgG antibodies.

13. The method of claim 1 further comprising the step of treating the patient identified as having Epstein Barr Abortive Lytic Replication with an antiviral agent.

14. The method of claim 13, wherein the antiviral agent is an antiviral nucleoside.

15. The method of claim 13, wherein the antiviral agent is one or more of valacyclovir, valganciclovir, maribavir, famciclovir, or foscarnet.