Methods and reagents for diagnosing rheumatoid arthrtis

• US 9,528,998 B2
• Filed: 04/14/2011
• Issued: 12/27/2016
• Est. Priority Date: 04/16/2010
• Status: Expired due to Fees

• Current Assignee: Abbott Japan Co., Ltd. (Abbott Laboratories)
• Original Assignee: Abbott Laboratories
• Inventors: Yoshimura, Toru, Chiba, Ryotaro
• Primary Examiner(s): Gabel, Gail R
• Application Number:
  US13/086,528
• Publication Number:
  US 20110256636A1
• Time in Patent Office: 2,084 Days
• Field of Search: 435/7.1, 435/7.21, 435/7.24, 435/7.4, 435/7.92, 435/7.94, 435/23, 435/973, 435/975, 546/501, 546/506, 546/509, 546/518, 546/523, 546/164, 546/172, 546/811, 530/388.23, 530/388.24, 530/388.25, 530/388.26, 530/388.7, 530/389.2, 530/389.3, 530/389.6, 530/391.1, 530/391.3
• US Class Current: 1/1
• CPC Class Codes: G01N 2800/102 Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints
• CPC Class Codes: G01N 33/6803 General methods of protein analysis not limited to specific proteins or families of proteins
• CPC Class Codes: G01N 33/6854 Immunoglobulins
• CPC Class Codes: G01N 33/6863 Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors

Abstract

Methods for diagnosing rheumatoid arthritis (RA) are disclosed, using measurement of the CCL8 protein level in a test sample from a subject. Testing for CCL8 as an indicator of RA can be combined with testing for other indicators of RA, including clinical assessments, imaging or other RA markers such as Rheumatoid factor (RF). CCL8 testing can be used for discriminating RA from other diseases or conditions, evaluating the severity of RA. Related diagnostic reagents, kits, pharmaceutical compositions, and methods for identifying a candidate substance as a therapeutic agent for treating rheumatoid arthritis are also described.

Claims

1. A method for diagnosing and treating rheumatoid arthritis in a subject comprising:

a. measuring a level of chemokine c-c motif ligand 8 (CCL8) protein in a serum sample obtained from the subject, wherein the level of CCL8 protein in the serum sample is measured by solid phase sandwich ELISA with an anti-CCL8 antibody and a plate reader;

b. assessing the subject for presence or absence of at least four of the following clinical indicators of rheumatoid arthritis;

(1) morning stiffness for at least one hour, (2) arthritis of three or more joint areas, (3) arthritis of hand joints, (4) symmetrical arthritis, (5) rheumatoid nodules, (6) serum rheumatoid factor (“

RF”

), or (7) radiographic changes;

c. detecting a level of CCL8 protein in the serum sample of the subject that is greater than 94 pg/mL and the presence of at least four clinical indicators of rheumatoid arthritis selected from step b. in the subject to thereby determine the presence of rheumatoid arthritis in the subject; and

d. administering a composition comprising an anti-CCL8 antibody or an antigen-binding fragment of the anti-CCL8 antibody at a concentration effective to treat the subject when the subject is determined to have rheumatoid arthritis according to step (c).

2. The method according to claim 1, further comprising measuring a level of one or more markers of rheumatoid arthritis in the serum sample, wherein the markers are selected from the group consisting of:

C-reactive protein (CRP), anti-cyclic citrullinated peptide (a-CCP), anti-agalactosyl IgG antibody (CARF IgG), matrix metalloprotease 3 (MMP-3), and rheumatoid factor, and wherein the measured level of CCL8 protein in step c and an increased level of the one or more rheumatoid arthritis markers in the serum sample of the subject further indicates presence of rheumatoid arthritis in the subject.

3. A method for monitoring treatment of rheumatoid arthritis in a subject comprising:

a. measuring a first level of chemokine c-c motif ligand 8 (CCL8) protein in a first serum sample obtained from the subject before treatment and detecting a level of CCL8 protein that is greater than 94 pg/mL to determine presence of rheumatoid arthritis in the subject;

b. measuring a second level of CCL8 protein in a second serum sample obtained from the subject after the treatment begins;

c. comparing the measured first level of CCL8 protein in step a. and the measured second level of CCL8 protein in step b., wherein a second level of CCL8 protein that is lower than the first level of CCL8 protein is indicative of a therapeutic treatment of rheumatoid arthritis in the subject; and

d. altering the treatment in the subject if the measured second level of CCL8 protein is greater than 94 pg/mL, wherein altering the treatment includes administering a composition comprising an anti-CCL8 antibody or an antigen-binding fragment of the anti-CCL8 antibody at a concentration effective to treat the subject having rheumatoid arthritis,

wherein the levels of CCL8 protein in the first and second serum samples are measured by solid phase sandwich ELISA with an anti-CCL8 antibody and a plate reader.