Methods for Diagnosing, Staging, Predicting Risk for Developing and Identifying Treatment Responders for Rheumatoid Arthritis

Abstract

Disclosed are methods for diagnosing, staging, and predicting risk for developing rheumatoid arthritis and other inflammatory diseases, and methods for identifying treatment responders and non-responders.

1 . A method for predicting the risk for developing an inflammatory disorder in a subject, comprising:
 (a) obtaining a sample from the subject;   (b) determining a concentration of each of IL-17A, IL-17A/F, and IL-17F, and optionally one or more of IL-1β, IL-6, totMMP-9, proMMP-9, cTnI, and combinations thereof in the sample;   wherein when the subject has a concentration of IL-17A greater than about 0.18 pg/ml, of IL-17A/F greater than about 1.35 pg/ml or of IL-17F of greater than about 116 pg/ml, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder.   
     
     
         2 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A greater than about 0.18 pg/ml, of IL-17A/F greater than about 1.35 pg/ml and of IL-17F of greater than about 116 pg/ml, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         3 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A greater than about 0.18 pg/ml, of IL-17A/F greater than about 1.35 pg/ml or of IL-17F of greater than about 116 pg/ml, in combination with one or more of a concentration of IL-1β less than healthy volunteer average concentrations for IL-1β, a concentration of IL-6 greater than healthy volunteer average concentrations for IL-6, or a concentration of totMMP-9 less than healthy volunteer average concentrations for totMMP-9, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         4 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A greater than about 0.18 pg/ml, of IL-17A/F greater than about 1.35 pg/ml and of IL-17F of greater than about 116 pg/ml, in combination with one or more of a concentration of IL-1β less than healthy volunteer average concentrations for IL-1β, a concentration of IL-6 greater than healthy volunteer average concentrations for IL-6, or a concentration of totMMP-9 less than healthy volunteer average concentrations for totMMP-9, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         5 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A greater than about 0.18 pg/ml, of IL-17A/F greater than about 1.35 pg/ml or of IL-17F of greater than about 116 pg/ml, in combination with a concentration of IL-1β less than healthy volunteer average concentrations for IL-1β, a concentration of IL-6 greater than healthy volunteer average concentrations for IL-6, and a concentration of totMMP-9 less than healthy volunteer average concentrations for totMMP-9, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         6 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A greater than about 0.18 pg/ml, of IL-17A/F greater than about 1.35 pg/ml and of IL-17F of greater than about 116 pg/ml, in combination with a concentration of IL-1β less than healthy volunteer average concentrations for IL-1β, a concentration of IL-6 greater than healthy volunteer average concentrations for IL-6, and a concentration of totMMP-9 less than healthy volunteer average concentrations for totMMP-9, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         7 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A, IL-17A/F and IL-17F greater than healthy volunteer average concentrations for IL-17A, IL-17A/F and IL-17F, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         8 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A, IL-17A/F or IL-17F greater than healthy volunteer average concentrations for IL-17A, IL-17A/F or IL-17F, in combination with one or more of a concentration of IL-1β less than healthy volunteer average concentrations for IL-1β, a concentration of IL-6 greater than healthy volunteer average concentrations for IL-6, or a concentration of totMMP-9 less than healthy volunteer average concentrations for totMMP-9, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         9 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A, IL-17A/F or IL-17F greater than healthy volunteer average concentrations for IL-17A, IL-17A/F or IL-17F, in combination with a concentration of IL-1β less than healthy volunteer average concentrations for IL-1β, a concentration of IL-6 greater than healthy volunteer average concentrations for IL-6, and a concentration of totMMP-9 less than healthy volunteer average concentrations for totMMP-9, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         10 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A, IL-17A/F and IL-17F greater than healthy volunteer average concentrations for IL-17A, IL-17A/F and IL-17F, in combination with one or more of a concentration of IL-1β less than healthy volunteer average concentrations for IL-1β, a concentration of IL-6 greater than healthy volunteer average concentrations for IL-6, or a concentration of totMMP-9 less than healthy volunteer average concentrations for totMMP-9, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         11 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A, IL-17A/F and IL-17F greater than healthy volunteer average concentrations for IL-17A, IL-17A/F and IL-17F, in combination with a concentration of IL-1β less than healthy volunteer average concentrations for IL-1β, a concentration of IL-6 greater than healthy volunteer average concentrations for IL-6, and a concentration of totMMP-9 less than healthy volunteer average concentrations for totMMP-9, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         12 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A greater than about 0.18 pg/ml, of IL-17A/F greater than about 1.35 pg/ml or of IL-17F of greater than about 116 pg/ml, in combination with one or more of a concentration of IL-1β less than about 1.1 pg/ml, a concentration of IL-6 greater than about 1.0 pg/ml, or a concentration of totMMP-9 less than about 5.0 ng/ml, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         13 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A greater than about 0.18 pg/ml, of IL-17A/F greater than about 1.35 pg/ml and of IL-17F of greater than about 116 pg/ml, in combination with one or more of a concentration of IL-1β less than about 1.1 pg/ml, a concentration of IL-6 greater than about 1.0 pg/ml, or a concentration of totMMP-9 less than about 5.0 ng/ml, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         14 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A greater than about 0.18 pg/ml, of IL-17A/F greater than about 1.35 pg/ml or of IL-17F of greater than about 116 pg/ml, in combination with a concentration of IL-1β less than about 1.1 pg/ml, a concentration of IL-6 greater than about 1.0 pg/ml, and a concentration of totMMP-9 less than about 5.0 ng/ml, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         15 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A greater than about 0.18 pg/ml, of IL-17A/F greater than about 1.35 pg/ml and of IL-17F of greater than about 116 pg/ml, in combination with a concentration of IL-1β less than about 1.1 pg/ml, a concentration of IL-6 greater than about 1.0 pg/ml, and a concentration of totMMP-9 less than about 5.0 ng/ml, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         16 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A, IL-17A/F or IL-17F greater than healthy volunteer average concentrations for IL-17A, IL-17A/F or IL-17F, in combination with one or more of a concentration of IL-1β less than about 1.1 pg/ml, a concentration of IL-6 greater than about 1.0 pg/ml, or a concentration of totMMP-9 less than about 5.0 ng/ml, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         17 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A, IL-17A/F or IL-17F greater than healthy volunteer average concentrations for IL-17A, IL-17A/F or IL-17F, in combination with a concentration of IL-1β less than about 1.1 pg/ml, a concentration of IL-6 greater than about 1.0 pg/ml, and a concentration of totMMP-9 less than about 5.0 ng/ml, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         18 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A, IL-17A/F and IL-17F greater than healthy volunteer average concentrations for IL-17A, IL-17A/F and IL-17F, in combination with one or more of a concentration of IL-1β less than about 1.1 pg/ml, a concentration of IL-6 greater than about 1.0 pg/ml, or a concentration of totMMP-9 less than about 5.0 ng/ml, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         19 . The method of  claim 1 , wherein when the subject has a concentration of IL-17A, IL-17A/F and IL-17F greater than healthy volunteer average concentrations for IL-17A, IL-17A/F and IL-17F, in combination with a concentration of IL-1β less than about 1.1 pg/ml, a concentration of IL-6 greater than about 1.0 pg/ml, and a concentration of totMMP-9 less than about 5.0 ng/ml, the subject is predicted to have a greater than normal risk of developing an inflammatory disorder. 
     
     
         20 - 38 . (canceled) 
     
     
         39 . A method for identifying an inflammatory disorder patient who responds to therapy, comprising:
 (a) obtaining a first sample from the patient;   (b) determining a first concentration of each of IL-17A, IL-17A/F, and IL-17F, and optionally one or more of IL-1β, IL-6, totMMP-9, proMMP-9, cTnI, and combinations thereof in the first sample;   (c) administering a therapy to the patient;   (d) obtaining a second sample from the patient; and   (e) determining a second concentration of each of IL-17A, IL-17A/F, and IL-17F, and optionally one or more of IL-1β, IL-6, totMMP-9, proMMP-9, cTnI, and combinations thereof in the second sample;   wherein when the inflammatory disorder patient has a first concentration of IL-17A greater than about 0.18 pg/ml, of IL-17A/F greater than about 1.35 pg/ml or of IL-17F of greater than about 116 pg/ml, and a second concentration of IL-17A less than about 0.18 pg/ml, of IL-17A/F less than about 1.35 pg/ml or of IL-17F of less than about 116 pg/ml, the inflammatory disorder patient is identified as a patient who responds to therapy.   
     
     
         40 . The method of  claim 39 , wherein when the patient has a first concentration of IL-17A greater than about 0.18 pg/ml, of IL-17A/F greater than about 1.35 pg/ml and of IL-17F of greater than about 116 pg/ml, and a second concentration of IL-17A less than about 0.18 pg/ml, of IL-17A/F less than about 1.35 pg/ml and of IL-17F of less than about 116 pg/ml, the inflammatory disorder patient is identified as a patient who responds to therapy. 
     
     
         41 . The method of  claim 39 , wherein when the patient has a first concentration of IL-17A greater than about 0.18 pg/ml, of IL-17A/F greater than about 1.35 pg/ml or of IL-17F of greater than about 116 pg/ml, in combination with one or more of a concentration of IL-1β less than healthy volunteer average concentrations for IL-1β, a concentration of IL-6 greater than healthy volunteer average concentrations for IL-6, or a concentration of totMMP-9 less than healthy volunteer average concentrations for totMMP-9, and a second concentration of IL-17A less than about 0.18 pg/ml, of IL-17A/F less than about 1.35 pg/ml or of IL-17F of less than about 116 pg/ml, in combination with one or more of a concentration of IL-1β substantially the same as healthy volunteer average concentrations for IL-1β, a concentration of IL-6 substantially the same as healthy volunteer average concentrations for IL-6, or a concentration of totMMP-9 substantially the same as healthy volunteer average concentrations for totMMP-9, the inflammatory disorder patient is identified as a patient who responds to therapy. 
     
     
         42 . The method of  claim 39 , wherein when the patient has a first concentration of IL-17A greater than about 0.18 pg/ml, of IL-17A/F greater than about 1.35 pg/ml and of IL-17F of greater than about 116 pg/ml, in combination with one or more of a concentration of IL-1β less than healthy volunteer average concentrations for IL-1β, a concentration of IL-6 greater than healthy volunteer average concentrations for IL-6, or a concentration of totMMP-9 less than healthy volunteer average concentrations for totMMP-9, and a second concentration of IL-17A less than about 0.18 pg/ml, of IL-17A/F less than about 1.35 pg/ml and of IL-17F of less than about 116 pg/ml, in combination with one or more of a concentration of IL-1β substantially the same as healthy volunteer average concentrations for IL-1β, a concentration of IL-6 substantially the same as healthy volunteer average concentrations for IL-6, or a concentration of totMMP-9 substantially the same as healthy volunteer average concentrations for totMMP-9, the inflammatory disorder patient is identified as a patient who responds to therapy. 
     
     
         43 . The method of  claim 39 , wherein when the patient has a first concentration of IL-17A greater than about 0.18 pg/ml, of IL-17A/F greater than about 1.35 pg/ml or of IL-17F of greater than about 116 pg/ml, in combination with a concentration of IL-1β less than healthy volunteer average concentrations for IL-1β, a concentration of IL-6 greater than healthy volunteer average concentrations for IL-6, and a concentration of totMMP-9 less than healthy volunteer average concentrations for totMMP-9, and a second concentration of IL-17A less than about 0.18 pg/ml, of IL-17A/F less than about 1.35 pg/ml or of IL-17F of less than about 116 pg/ml, in combination with a concentration of IL-1β substantially the same as healthy volunteer average concentrations for IL-1β, a concentration of IL-6 substantially the same as healthy volunteer average concentrations for IL-6, and a concentration of totMMP-9 substantially the same as healthy volunteer average concentrations for totMMP-9, the inflammatory disorder patient is identified as a patient who responds to therapy. 
     
     
         44 . The method of  claim 39 , wherein when the patient has a first concentration of IL-17A greater than about 0.18 pg/ml, of IL-17A/F greater than about 1.35 pg/ml and of IL-17F of greater than about 116 pg/ml, in combination with a concentration of IL-1β less than healthy volunteer average concentrations for IL-1β, a concentration of IL-6 greater than healthy volunteer average concentrations for IL-6, and a concentration of totMMP-9 less than healthy volunteer average concentrations for totMMP-9, and a second concentration of IL-17A less than about 0.18 pg/ml, of IL-17A/F less than about 1.35 pg/ml or of IL-17F of less than about 116 pg/ml, in combination with a concentration of IL-1β substantially the same as healthy volunteer average concentrations for IL-1β, a concentration of IL-6 substantially the same as healthy volunteer average concentrations for IL-6, and a concentration of totMMP-9 substantially the same as healthy volunteer average concentrations for totMMP-9, the inflammatory disorder patient is identified as a patient who responds to therapy. 
     
     
         45 . The method of  claim 39 , wherein when the patient has a first concentration of IL-17A, IL-17A/F or IL-17F greater than healthy volunteer average concentrations for IL-17A, IL-17A/F or IL-17F, and a second concentration of one or more of IL-17A, IL-17A/F or IL-17F substantially the same as healthy volunteer concentrations for IL-17A, IL-17A/F or IL-17F, the inflammatory disorder patient is identified as a patient who responds to therapy. 
     
     
         46 . The method of  claim 39 , wherein when the patient has a first concentration of IL-17A, IL-17A/F and IL-17F greater than healthy volunteer average concentrations for IL-17A, IL-17A/F and IL-17F, and a second concentration of IL-17A, IL-17A/F and IL-17F substantially the same as healthy volunteer concentrations for IL-17A, IL-17A/F and IL-17F, the inflammatory disorder patient is identified as a patient who responds to therapy. 
     
     
         47 . The method of  claim 39 , wherein when the patient has a first concentration of IL-17A, IL-17A/F or IL-17F greater than healthy volunteer average concentrations for IL-17A, IL-17A/F or IL-17F, in combination with one or more of a concentration of IL-1β less than healthy volunteer average concentrations for IL-1β, a concentration of IL-6 greater than healthy volunteer average concentrations for IL-6, or a concentration of totMMP-9 less than healthy volunteer average concentrations for totMMP-9, and a second concentration of IL-17A, IL-17A/F or IL-17F substantially the same as healthy volunteer concentrations for IL-17A, IL-17A/F or IL-17F, in combination with one or more of a concentration of IL-1β substantially the same as healthy volunteer average concentrations for IL-1β, a concentration of IL-6 substantially the same as healthy volunteer average concentrations for IL-6, or a concentration of totMMP-9 substantially the same as healthy volunteer average concentrations for totMMP-9, the inflammatory disorder patient is identified as a patient who responds to therapy. 
     
     
         48 . The method of  claim 39 , wherein when the patient has a first concentration of IL-17A, IL-17A/F or IL-17F greater than healthy volunteer average concentrations for IL-17A, IL-17A/F and IL-17F, in combination with a concentration of IL-1β less than healthy volunteer average concentrations for IL-1β, a concentration of IL-6 greater than healthy volunteer average concentrations for IL-6, and a concentration of totMMP-9 less than healthy volunteer average concentrations for totMMP-9, and a second concentration of IL-17A, IL-17A/F or IL-17F substantially the same as healthy volunteer concentrations for IL-17A, IL-17A/F or IL-17F, in combination with a concentration of IL-1β substantially the same as healthy volunteer average concentrations for IL-1β, a concentration of IL-6 substantially the same as healthy volunteer average concentrations for IL-6, and a concentration of totMMP-9 substantially the same as healthy volunteer average concentrations for totMMP-9, the inflammatory disorder patient is identified as a patient who responds to therapy. 
     
     
         49 . The method of  claim 39 , wherein when the patient has a first concentration of IL-17A, IL-17A/F and IL-17F greater than healthy volunteer average concentrations for IL-17A, IL-17A/F and IL-17F, in combination with one or more of a concentration of IL-1β less than healthy volunteer average concentrations for IL-1β, a concentration of IL-6 greater than healthy volunteer average concentrations for IL-6, or a concentration of totMMP-9 less than healthy volunteer average concentrations for totMMP-9, and a second concentration of IL-17A, IL-17A/F and IL-17F substantially the same as healthy volunteer concentrations for IL-17A, IL-17A/F and IL-17F, in combination with one or more of a concentration of IL-1β substantially the same as healthy volunteer average concentrations for IL-1β, a concentration of IL-6 substantially the same as healthy volunteer average concentrations for IL-6, or a concentration of totMMP-9 substantially the same as healthy volunteer average concentrations for totMMP-9, the inflammatory disorder patient is identified as a patient who responds to therapy. 
     
     
         50 . The method of  claim 39 , wherein when the patient has a first concentration of IL-17A, IL-17A/F and IL-17F greater than healthy volunteer average concentrations for IL-17A, IL-17A/F and IL-17F, in combination with a concentration of IL-1β less than healthy volunteer average concentrations for IL-1β, a concentration of IL-6 greater than healthy volunteer average concentrations for IL-6, and a concentration of totMMP-9 less than healthy volunteer average concentrations for totMMP-9, and a second concentration of IL-17A, IL-17A/F and IL-17F substantially the same as healthy volunteer concentrations for IL-17A, IL-17A/F and IL-17F, in combination with a concentration of IL-1β substantially the same as healthy volunteer average concentrations for IL-1β, a concentration of IL-6 substantially the same as healthy volunteer average concentrations for IL-6, and a concentration of totMMP-9 substantially the same as healthy volunteer average concentrations for totMMP-9, the inflammatory disorder patient is identified as a patient who responds to therapy. 
     
     
         51 . The method of  claim 39 , wherein when the patient has a first concentration of IL-17A greater than about 0.18 pg/ml, of IL-17A/F greater than about 1.35 pg/ml or of IL-17F of greater than about 116 pg/ml, in combination with one or more of a concentration of IL-1β less than about 1.1 pg/ml, a concentration of IL-6 greater than about 1.0 pg/ml, or a concentration of totMMP-9 less than about 5.0 ng/ml, and a second concentration of IL-17A less than about 0.18 pg/ml, of IL-17A/F less than about 1.35 pg/ml or of IL-17F of less than about 116 pg/ml, in combination with one or more of a concentration of IL-1β greater than about 1.1 pg/ml, a concentration of IL-6 less than about 1.0 pg/ml, or a concentration of totMMP-9 greater than about 5.0 ng/ml, the inflammatory disorder patient is identified as a patient who responds to therapy. 
     
     
         52 - 59 . (canceled) 
     
     
         60 . The method of  claim 1 , wherein the inflammatory disorder is Rheumatoid Arthritis. 
     
     
         61 . The method of  claim 1 , wherein the inflammatory disorder is Crohn's Disease. 
     
     
         62 . The method of  claim 1 , wherein the inflammatory disorder is Inflammatory Bowel Disease. 
     
     
         63 . The method of  claim 1 , wherein the inflammatory disorder is ulcerative colitis. 
     
     
         64 . The method of  claim 1 , wherein the inflammatory disorder is psoriasis. 
     
     
         65 . The method of  claim 1 , wherein the inflammatory disorder is Chronic Obstructive Pulmonary Disease. 
     
     
         66 - 83 . (canceled) 
     
     
         84 . The method of  claim 39 , wherein the inflammatory disorder is Rheumatoid Arthritis. 
     
     
         85 . The method of  claim 39 , wherein the inflammatory disorder is Crohn's Disease. 
     
     
         86 . The method of  claim 39 , wherein the inflammatory disorder is Inflammatory Bowel Disease. 
     
     
         87 . The method of  claim 39 , wherein the inflammatory disorder is ulcerative colitis. 
     
     
         88 . The method of  claim 39 , wherein the inflammatory disorder is psoriasis. 
     
     
         89 . The method of  claim 39 , wherein the inflammatory disorder is Chronic Obstructive Pulmonary Disease.