The Immunosignature of Canine Lymphoma Characterization and Diagnostic Application

2015-01-13

Prepared document for publication by Bart Legutki

"C:\Users\kurtw_000\Documents\kurt\storage\CIM Research Folder\DR\2014\04-04-2014d0915\Johnston et al manuscript 15AUG2013 for CCR fig to sup.doc"

notes
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Despite being a clonal disease, both an individual immunosignature and a generalized lymphoma immunosignature were observed in each dog
-The general lymphoma immunosignature identified in the initial set of dogs (n=32) was able to predict health status in an independent set of dogs (n=42, 97% accuracy).  
-immunosignature at diagnosis was able to predict which dogs with B cell lymphoma were going to relapse in less than 120 days (n=33, 97% accuracy).
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if 106 initiating cancer cells release 1000 molecules each of a biomarker into two liters of blood at steady state, the concentration of this biomarker would only be 1.3 x10-14 M (7), placing it below the detection limits of even the best assays 
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Arising early in the course of a disease, the activation of a single B cell results in an ~10^11 amplification of signal in only a week (10).  
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Per chip median normalized values were ComBat normalized to remove batch effects 
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The 340 peptides selected above to separate LSA and healthy clearly separated the expanded test set of dogs, even though the print run and anti-IgG secondary antibody were different 
--impressive
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When the training set arrays from print run 1 were used to predict the test set from print run 2, the accuracy was 97%: one LSA-B patient was miscalled as healthy
-he tried splitting on gender and age (the age was just split down the middle from age 7), and he was unable to classify well. . supporting the validity of the LSA immunosignature
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The Immunosignature Can Distinguish Dogs with T cell Lymphoma From Those With B cell Lymphoma.  
-immunophenotyping
-they identified a unique part of the immunosignature (6 to 8 peptides) specific to each dog for the B cell LSA
-Monitoring the Immunosignature Present at Diagnosis Marks Remission but Not Relapse.  
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For the 177 peptides increased in B cell LSA, a median of 25 +/- 14 peptides (14%) decreased at remission and 13 +/- 7 peptides increased from remission to relapse.  
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Of the 173 peptides increased in T cell LSA, a median of 35 +/- 20 peptides (20%) decreased upon remission and a median of 21.4 +/- 6 peptides (12%) increased between remission and relapse.  
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Taken together, this indicates that the immunosignature can verify remission through the personalized signature, but other means are needed to detect recurrence.
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The median raw feature intensity of the arrays probed with B cell LSA were significantly lower (p = 1x10-4)) than those probed with healthy donors (Figure S2a).  
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Entropy in LSA-B patients was significantly decreased (Figure S2b), suggesting that the circulating antibody repertoire was driven to a reduced distribution of antibody species and by extension over representation of the producing B cell clones.   
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The Immunosignature of B cell LSA at Diagnosis is Capable of Predicting Length of Disease Free Interval in Dogs Entering Remission.

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