The Immunosignature of Canine Lymphoma Characterization and Diagnostic Application
2015-01-13
The Immunosignature of Canine Lymphoma Characterization and Diagnostic Application
Prepared document for publication by Bart Legutki
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notes
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).
- q
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
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).
Per chip median normalized values were ComBat normalized to remove batch effects
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
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
- q
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.
- q
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.
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.
Taken together, this indicates that the immunosignature can verify remission through the personalized signature, but other means are needed to detect recurrence.
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).
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.
The Immunosignature of B cell LSA at Diagnosis is Capable of Predicting Length of Disease Free Interval in Dogs Entering Remission.