Biomarkers and methods for assessing psoriatic arthritis disease activity

Abstract

Provided herein are biomarkers and methods for generating scores useful for assessing psoriatic arthritis (PsA) disease activity in subjects previously diagnosed with PsA. The invention also provides predictive model methods based on the biomarkers, as well as computer systems, software embodiments of the models for scoring and optionally classifying samples, and methods of recommending optimal therapeutic regimens.

What is claimed is: 
     
         1 .- 17 . (canceled) 
     
     
         18 . A method for generating a protein level score comprising:
 performing at least one immunoassay on a first blood sample from a subject previously diagnosed with psoriatic arthritis (PsA), to generate protein level data for each protein marker of a plurality of protein markers, wherein the plurality of protein markers comprises a plurality of test markers comprising at least four markers selected from chitinase 3-like 1 (cartilage glycoprotein-39) (CHI3L1); C-reactive protein, pentraxin-related (CRP); epidermal growth factor (beta-urogastrone) (EGF); interleukin 6 (interferon, beta 2) (IL6); leptin (LEP); matrix metallopeptidase 1 (interstitial collagenase) (MMP1); matrix metallopeptidase 3 (stromelysin 1, progelatinase) (MMP3); resistin (RETN); serum amyloid A1 (SAA1); tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A); vascular cell adhesion molecule 1 (VCAM1); or, vascular endothelial growth factor A (VEGFA); and   combining the protein level data for each test marker to generate the protein level score.   
     
     
         19 . The method of  claim 18 , wherein performance of the at least one immunoassay comprises:
 obtaining the first blood sample, wherein the first blood sample comprises the protein markers;   contacting the first blood sample with a plurality of distinct reagents;   generating a plurality of distinct complexes between the reagents and markers; and   detecting the complexes to generate the data.   
     
     
         20 . The method of  claim 18 , wherein the at least one immunoassay comprises a multiplex assay. 
     
     
         21 . The method of  claim 18 , wherein the at least four protein markers comprise at least five markers selected from CHI3L1, CRP, EGF, IL6, LEP, MMP1, MMP3, RETN, SAA1, TNFRSF1A, VCAM1, or VEGFA. 
     
     
         22 . The method of  claim 18 , wherein the at least four protein markers comprise at least six markers selected from CHI3L1, CRP, EGF, IL6, LEP, MMP1, MMP3, RETN, SAA1, TNFRSF1A, VCAM1, or VEGFA. 
     
     
         23 . The method of  claim 18 , wherein the at least four protein markers comprise at least seven markers selected from CHI3L1, CRP, EGF, IL6, LEP, MMP1, MMP3, RETN, SAA1, TNFRSF1A, VCAM1, or VEGFA. 
     
     
         24 . The method of  claim 18 , wherein the at least four protein markers comprise at least eight markers selected from CHI3L1, CRP, EGF, IL6, LEP, MMP1, MMP3, RETN, SAA1, TNFRSF1A, VCAM1, or VEGFA. 
     
     
         25 .- 27 . (canceled) 
     
     
         28 . The method of  claim 18 , wherein the plurality of test markers comprises CHI3L1, CRP, EGF, IL6, LEP, MMP1, MMP3, RETN, SAA1, TNFRSF1A, VCAM1, and VEGFA. 
     
     
         29 . The method of  claim 18 , wherein the CHI3L1 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_001267.2, wherein the CRP is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_000558.2, wherein the EGF is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_001954.2, wherein the IL6 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_000591.1, wherein the LEP is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_000221.1, wherein the MMP1 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_002412.1, wherein the MMP3 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_002413.1, wherein the RETN is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_065148.1, wherein the SAA1 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_000322.2, wherein the TNFRSF1A is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_001056.1, wherein the VCAM1 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_001069.1, and wherein the VEGFA is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_001020539.2. 
     
     
         30 . A method for providing a quantitative measure of psoriatic arthritis (PsA) disease activity in a subject previously diagnosed with PsA comprising:
 performing at least one immunoassay on a first sample from the subject to generate a first dataset comprising quantitative data comprising at least four markers selected from chitinase 3-like 1 (cartilage glycoprotein-39) (CHI3L1); C-reactive protein, pentraxin-related (CRP);   epidermal growth factor (beta-urogastrone) (EGF); interleukin 6 (interferon, beta 2) (IL6); leptin (LEP); matrix metallopeptidase 1 (interstitial collagenase) (MMP1); matrix metallopeptidase 3 (stromelysin 1, progelatinase) (MMP3); resistin (RETN); serum amyloid A1 (SAA1); tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A); vascular cell adhesion molecule 1 (VCAM1); or, vascular endothelial growth factor A (VEGFA); and   applying an algorithm to said first dataset to determine a first disease activity score, wherein said first disease activity score provides a quantitative measure of PsA disease activity in said subject.   
     
     
         31 . The method of  claim 30 , further comprising:
 receiving a second dataset associated with a second sample obtained from the subject, wherein the first sample and the second sample are obtained from the subject at different times;   applying the algorithm to the second dataset to determine a second disease activity score; and   comparing the first disease activity score and said second disease activity score to determine a change in the disease activity scores, therein the change indicates a change in the psoriatic arthritis disease activity the subject.   
     
     
         32 . The method of  claim 30 , wherein the at least four protein markers comprise at least five, six, seven, eight, nine, ten, or eleven markers selected from CHI3L1, CRP, EGF, IL6, LEP, MMP1, MMP3, RETN, SAA1, TNFRSF1A, VCAM1, or VEGFA. 
     
     
         33 . The method of  claim 30 , wherein the CHI3L1 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_001267.2, wherein the CRP is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_000558.2, wherein the EGF is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_001954.2, wherein the IL6 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_000591.1, wherein the LEP is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_000221.1, wherein the MMP1 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_002412.1, wherein the MMP3 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_002413.1, wherein the RETN is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_065148.1, wherein the SAA1 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_000322.2, wherein the TNFRSF1A is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_001056.1, wherein the VCAM1 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_001069.1, and wherein the VEGFA is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_001020539.2. 
     
     
         34 .- 36 . (canceled) 
     
     
         37 . A method for recommending a therapeutic regimen in a subject previously diagnosed with psoriatic arthritis (PsA), the method comprising:
 a) performing, at a first time point, a first immunoassay on a first sample from the subject to generate a first score based on a first set of quantitative data, wherein the first set of quantitative data comprises expression data for at least four biomarkers selected from chitinase 3-like 1 (cartilage glycoprotein-39) (CHI3L1); C-reactive protein, pentraxin-related (CRP); epidermal growth factor (beta-urogastrone) (EGF); interleukin 6 (interferon, beta 2) (IL6); leptin (LEP);   matrix metallopeptidase 1 (interstitial collagenase) (MMP1); matrix metallopeptidase 3 (stromelysin 1, progelatinase) (MMP3); resistin (RETN); serum amyloid A1 (SAA1); tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A); vascular cell adhesion molecule 1 (VCAM1); or, vascular endothelial growth factor A (VEGFA);
 b) performing, at a second time point that is a time period after the first time point, a second immunoassay on a second sample from the subject to generate a second score based on a second set of quantitative data, wherein the second set of quantitative data comprises expression data for the at least four biomarkers; 
 c) determining whether there is a difference between the first score and the second score; and 
   d) recommending a therapeutic regimen, or modifying an existing therapeutic regimen, based on the difference between the first and second scores.   
     
     
         38 . The method of  claim 37  wherein a non-biologic therapeutic regimen is recommended if the difference between the first and second scores indicate a reduction or no change in PsA disease activity. 
     
     
         39 . The method of  claim 37  wherein a biologic therapeutic regimen is recommended if the difference between the first and second scores indicate an increase in PsA disease activity. 
     
     
         40 . The method of  claim 37 , wherein performance of the at least one immunoassay comprises:
 obtaining the first sample, wherein the first sample comprises the protein markers;   contacting the first sample with a plurality of distinct reagents;
 generating a plurality of distinct complexes between the reagents and markers; and 
 detecting the complexes to generate the data. 
   
     
     
         41 . The method of  claim 37 , wherein the first and second immunoassays comprise a multiplex assay. 
     
     
         42 . The method of  claim 37 , wherein the at least four protein markers comprise at least five, six, seven, eight, nine, ten, or eleven markers selected from CHI3L1, CRP, EGF, IL6, LEP, MMP1, MMP3, RETN, SAA1, TNFRSF1A, VCAM1, or VEGFA. 
     
     
         43 . The method of  claim 37 , wherein the CHI3L1 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_001267.2, wherein the CRP is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_000558.2, wherein the EGF is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_001954.2, wherein the IL6 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_000591.1, wherein the LEP is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_000221.1, wherein the MMP1 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_002412.1, wherein the MMP3 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_002413.1, wherein the RETN is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_065148.1, wherein the SAA1 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_000322.2, wherein the TNFRSF1A is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_001056.1, wherein the VCAM1 is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_001069.1, and wherein the VEGFA is at least 90% identical to the amino acid sequence of NCBI RefSeq NP_001020539.2.