Causative agents and diagnostic methods relating to rheumatoid arthritis

Patent metadata

Field	Value
Publication number	US-10011883-B2
Application number	US-201214351622-A
Country	US
Kind code	B2
Filing date	Oct 15, 2012
Priority date	Oct 14, 2011
Publication date	Jul 3, 2018
Grant date	Jul 3, 2018

Abstract

Methods, reagents and compositions thereof for predicting RA onset in susceptible individuals, diagnosing RA onset, and/or evaluating efficacy of a therapeutic regimen for treating RA are described herein. Determining the amount of a particular bacterial species comprising SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3 (SEQ ID NO: 1+ bacteria) serves as a biomarker for the above indications.

First claim

What is claimed is:

1. A method for diagnosing and treating new onset rheumatoid arthritis (NORA) in a subject, the method comprising:
a) obtaining a biological sample from the subject;
b) detecting in the biological sample an increased amount of a Prevotella -related species of bacteria relative to that of a biological sample obtained from a control subject, wherein the Prevotella -related species of bacteria comprises SEQ ID NO: 1 or a variant thereof SEQ ID NO: 2 or SEQ ID NO: 3, thereby diagnosing NORA in the subject; and
c) administering a nonsteroidal anti-inflammatory drug (NSAID), a disease-modifying anti-rheumatic drug (DMARD), a steroid, an antibiotic, or an analgesic to the subject diagnosed with NORA.

2. The method of claim 1 , wherein the subject has a familial history of RA and/or exhibits at least one of the seven diagnostic criteria used to diagnose RA selected from the group consisting of morning stiffness in and around joints lasting at least 1 hour before maximal improvement; soft tissue swelling of 3 or more joint areas observed by a physician; swelling of the hand joints; symmetric swelling; rheumatoid nodules; elevated levels of serum rheumatoid factor (RF); and radiographic changes in hand and/or wrist joints.

3. The method of claim 1 , wherein the biological sample is fecal material, biopsies of specific organ tissues, synovial fluid, or synovial fluid biopsies.

4. The method of claim 3 , wherein the specific organ tissues comprise large and small intestinal biopsies.

5. The method of claim 1 , wherein the amount of the Prevotella -related species of bacteria is determined by nucleic acid sequencing.

6. The method of claim 5 , wherein the nucleic acid sequencing is massively parallel 16S rRNA pyrosequencing.

7. The method of claim 5 , wherein the nucleic acid sequencing detects 16S rRNA comprising SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3 and the amount of the 16S rRNA comprising SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3 is indicative of the amount of Prevotella -related species of bacteria in the biological sample.

8. The method of claim 1 , wherein the Prevotella -related species of bacteria is P. copri.

9. The method of claim 1 , wherein the amount of the Prevotella -related species of bacteria is detected using a reagent that specifically binds to the Prevotella -related species of bacteria or a nucleic acid sequence thereof.

10. The method of claim 9 , wherein the reagent is selected from the group consisting of an antibody, an antibody derivative, an antibody fragment, a nucleic acid probe, an oligonucleotide, and an oligonucleotide primer pair specific for Prevotella -related species of bacteria comprising SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.

11. The method of claim 9 , wherein the reagent is an oligonucleotide primer pair of SEQ ID NO: 4 and SEQ ID NO: 5.

12. The method of claim 9 , wherein detecting of the increased amount of the Prevotella -related species of bacteria includes at least one assay selected from the group consisting of nucleic acid sequencing, PCR amplification, a competitive binding assay, a non-competitive binding assay, a radioimmunoassay, immunohistochemistry, an enzyme-linked immunosorbent assay (ELISA), a sandwich assay, a gel diffusion immunodiffusion assay, an agglutination assay, dot blotting, a fluorescent immunoassay such as fluorescence-activated cell sorting (FACS), a chemiluminescence immunoassay, an immunoPCR immunoassay, a protein A or protein G immunoassay, and an immunoelectrophoresis assay.

13. The method of claim 1 , further comprising processing the biological sample and analyzing the processed biological sample generated thereby to determine the amount of Prevotella -related species in the biological sample.

14. The method of claim 13 , wherein the processing comprises extracting nucleic acids from the biological sample.

15. The method of claim 1 , further comprising obtaining a sample of T cells from the subject to identify T cells specific for the Prevotella -related species of bacteria in the subject.

16. The method of claim 1 , wherein the disease-modifying anti-rheumatic drug (DMARD) is methotrexate.

Assignees

• Abramson Steven B
• Scher Jose U
• Littman Dan R
• Pamer Eric G
• Univ New York
• Memorial Sloan Kettering Cancer Center

Inventors

• Abramson Steven B
• Scher Jose U
• Littman Dan R
• Pamer Eric G
• Ubeda Carles
• Longman Randy S
• Sczesnak Andrew

Classifications

• C12Q2600/158

  Expression markers · CPC title

• C12Q1/6883

  for diseases caused by alterations of genetic material · CPC title

• G01N33/56911

  Bacteria · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title