Blood biomarkers for appendicitis and diagnostics methods using biomarkers

Abstract

The invention relates to methods and kits for diagnosing and/or treating appendicitis in a subject, comprising performing one or more assays configured to detect one or more biomarkers on a body fluid sample obtained from the subject to provide one or more assay result(s) and correlating the assay result(s) to the occurrence or nonoccurrence of appendicitis in the subject or likelihood of the future outcome to the subject.

1 . A method of diagnosing appendicitis in a subject, or assigning a likelihood of a future outcome to a subject diagnosed with appendicitis, comprising:
 performing one or more assays configured to detect one or more biomarkers selected from the group consisting of Chemokine C-X-C receptor 1, Interleukin 8 receptor β, Fc frag of IgG receptor IIIb (CD16b), MHC class II DR beta 5, Leukocyte IgG-like receptor A3, Defensin alpha 1, Defensin alpha 1B, Defensin alpha 3, 18S ribosomal RNA, CDC14A, 28S ribosomal RNA, 60S acidic ribosomal protein P1, 40S ribosomal protein S26, Ribosomal protein L23, Ribosomal protein L37a, Ribosomal protein S28, Alkaline phosphatase, Carbonic anhydrase IV, Neuroblastoma breakpoint family 10, Ninjurin 1, Prokineticin 2, Superoxide dismutase 2, LOC100129902, LOC100131205, LOC100131905, LOC100132291, LOC100132394, LOC100132742, LOC100134364, LOC391370, LOC646785, LOC644191 and C5orf32 on a body fluid sample obtained from the subject to provide one or more assay result(s); and   correlating the assay result(s) to the occurrence or nonoccurrence of appendicitis in the subject or likelihood of the future outcome to the subject.   
     
     
         2 . A method according to  claim 1 , wherein the performing step comprises introducing the body fluid sample obtained from the subject into an assay instrument which (i) contacts the body fluid sample with one or more binding reagents corresponding to the biomarker(s) being assayed, wherein each biomarker which is assayed binds to its respective specific binding reagent in an amount related to its concentration in the body fluid sample, (ii) generates one or more assay results indicative of binding of each biomarker which is assayed to its respective specific binding reagent; and (iii) displays the one or more assay results as a quantitative result in a human-readable form. 
     
     
         3 . A method according to  claim 2 , wherein the specific binding reagent is an antibody. 
     
     
         4 . A method according to  claim 1 , wherein the one or more assays are sandwich assays. 
     
     
         5 . A method according to  claim 1 , wherein the correlating step comprises comparing the assay result(s) or a value derived therefrom to a threshold selected in a population study to separate the population into a first subpopulation at higher predisposition for the occurrence of appendicitis or the future outcome, and a second subpopulation at lower predisposition for the occurrence of appendicitis or the future outcome relative to the first subpopulation. 
     
     
         6 . A method according to  claim 1 , further comprising treating the subject based on the predetermined subpopulation of individuals to which the patient is assigned, wherein if the patient is in the first subpopulation, the treatment comprises treating the subject for appendicitis or the future outcome. 
     
     
         7 . A method according to  claim 1 , wherein the future outcome is mortality. 
     
     
         8 . A method according to  claim 1 , wherein the subject is being evaluated for abdominal pain. 
     
     
         9 . A method according to  claim 1 , wherein the correlating step comprises determining the concentration of each biomarker which is assayed, and individually comparing each biomarker concentration to a corresponding threshold level for that biomarker. 
     
     
         10 . A method according to  claim 1 , wherein the assay instrument comprises a processing system configured to perform the correlating step and output the assay result(s) or a value derived therefrom in human readable form. 
     
     
         11 . A method according to  claim 2 , wherein a plurality of the biomarkers are measured, wherein the assay instrument performs the correlating step, which comprises determining the concentration of each of the plurality of biomarkers, calculating a single value based on the concentration of each of the plurality of biomarkers, comparing the single value to a corresponding threshold level and displaying an indication of whether the single value does or does not exceed its corresponding threshold in a human-readable form. 
     
     
         12 . A method according to  claim 1 , wherein method provides a sensitivity or specificity of at least 0.7 for the identification of appendicitis when compared to normal subjects. 
     
     
         13 . A method according to  claim 1 , wherein method provides a sensitivity or specificity of at least 0.7 for the identification of appendicitis when compared to subjects exhibiting symptoms that mimic appendicitis symptoms. 
     
     
         14 . A method according to  claim 1 , wherein the sample is selected from the group consisting of blood, serum, and plasma. 
     
     
         15 . A method according to  claim 1 , wherein the sample is urine. 
     
     
         16 . A method for evaluating biomarker levels in a body fluid sample, comprising:
 obtaining a body fluid sample from a subject selected for evaluation based on a determination that the subject is experiencing symptoms indicative of possible acute appendicitis; and   performing one or more analyte binding assays configured to detect one or more biomarkers selected from the group consisting of Chemokine C-X-C receptor 1, Interleukin 8 receptor β, Fc frag of IgG receptor IIIb (CD16b), MHC class II DR beta 5, Leukocyte IgG-like receptor A3, Defensin alpha 1, Defensin alpha 1B, Defensin alpha 3, 18S ribosomal RNA, CDC14A, 28S ribosomal RNA, 60S acidic ribosomal protein P1, 40S ribosomal protein S26, Ribosomal protein L23, Ribosomal protein L37a, Ribosomal protein S28, Alkaline phosphatase, Carbonic anhydrase IV, Neuroblastoma breakpoint family 10, Ninjurin 1, Prokineticin 2, Superoxide dismutase 2, LOC100129902, LOC100131205, LOC100131905, LOC100132291, LOC100132394, LOC100132742, LOC100134364, LOC391370, LOC646785, LOC644191 and C5orf32 by introducing the body fluid sample obtained from the subject into an assay instrument which   (i) contacts the body fluid sample with one or more binding reagents corresponding to the biomarker(s) being assayed, wherein each biomarker which is assayed binds to its respective specific binding reagent in an amount related to its concentration in the body fluid sample,   (ii) generates one or more assay results indicative of binding of each biomarker which is assayed to its respective specific binding reagent; and   (iii) displays the one or more assay results as a quantitative result in a human-readable form.   
     
     
         17 . A method according to  claim 16 , wherein the assay result(s) are displayed as a concentration of each biomarker which is assayed. 
     
     
         18 . A method according to  claim 17 , wherein the assay instrument further individually compares each biomarker concentration to a corresponding threshold level for that biomarker, and displays an indication of whether each biomarker does or does not exceed its corresponding threshold in a human-readable form. 
     
     
         19 . A method according to  claim 16 , wherein a plurality of the biomarkers are measured, and wherein the assay results(s) comprise a single value calculated using a function that converts the concentration of each of the plurality of biomarkers into a single value. 
     
     
         20 . A method according to  claim 19 , wherein the assay instrument further compares the single value to a corresponding threshold level and displays an indication of whether the single value does or does not exceed its corresponding threshold in a human-readable form. 
     
     
         21 - 27 . (canceled)