Urine Proteomics in Kawasaki Disease

Report
Urine Proteomics in
Kawasaki Disease
Pawan Sharma
15th October 2013
Kawasaki Disease
• Uncommonly common systemic vasculitis.
• 6 months to 4 years age.
• Significant mortality and morbidity esp with delayed
diagnosis.
• No pathognomic test for early diagnosis.
GOAL
To discover and validate diagnostic markers
of KD in a prospective cohort.
.
Study participants
• Over 39 months in Tertiary care hospital.
• Approved by Boston Children’s Hospital
Committee.
• Patients under the age of 18 with possible
diagnosis of KD.
• Exclusion criteria: neoplastic, renal or urologic
disease.
• Total patients mentioned 236 (234).
Study design
• Discovery phase.
• Validation phase:
First cohort based on possible KD, but before
determination of final diagnosis.
Second cohort utilized serum specimens collected
as a part of Pediatric Heart Network Study of KD.
Out come measures
• Paediatric Rheumatologist
• Use of Published Diagnostic Criteria for KD.
• Atypical KD was established using American Heart
association guideline.
DF candidate diagnostic marker
• Analysed 15 patients.
• 6 KD patients (3 with and 3 without Coronary heart
disease).
• 6 non-KD patients (2 non specific, 3 adeno and 1
Pyelonephritis).
• 3 matched specimen from treated patients with KD
(after 1 month).
• 190 proteins specific to KD.
• Meprin A and Filamin C chosen.
Urine proteomics for discovery of improved diagnostic markers of Kawasaki disease
EMBO Molecular Medicine
Volume 5, Issue 2, pages 210-220, 20 DEC 2012 DOI: 10.1002/emmm.201201494
http://onlinelibrary.wiley.com/doi/10.1002/emmm.201201494/full#fig1
Validation
•
•
•
•
•
Prospectively measured concentration in urine.
Investigators blinded to Final diagnosis.
Mean age 3 years.
53 (49%) final diagnosis of KD.
All treated with IVIg and Aspirin, 30% required
repeat treatment.
• All studied patients received a Final Outcome.
Table 2. Final diagnosis of the 107 study patients
Final diagnosis
Number of patients
Kawasaki disease
53 (49%)
Viral syndrome
33 (61%)
Adenovirus
6
Serum sickness
3
Pyelonephritis
2
group A streptococcal pharyngitis
2
Cytomegalovirus
1
Epstein-Barr virus
1
Group A streptococcal pharyngitis
1
Lyme disease
1
Otitis media
1
Pneumonia
1
Respiratory syncytial virus
1
Systemic arthritis
1
Mean values
KD
Non KD
Filamin C
19.2
3.7
Meprin A
50.2
5.6
Atypical KD
Non KD
Filamin C
17
3.7
Meprin A
41.5
5.6
Blinded case control study
Response to treatment
2nd Cohort
• 112 archived samples collected from KD patient
analysed.
• Compared them with Non-KD febrile illness.
• Serum samples used.
• Results were:
KD
Non KD
Filamin C
217
6.6
Meprin A
1363
14.8
Mouse model
What do we think
• Clear question for study address?
• Was there a comparison with appropriate
standard?
• Did all patients get diagnostic test and reference
standard?
• Could the result have been influenced?
• Is disease status clearly described?
• Were methods described in clear details?
• What are the results?
• Can the results be applied to our patients?
Summary
• Potential approaches for improving diagnosis.
• Discover phase: very small group.
• Mechanism of how this markers accumulate shall
be important direction for future work.
• Limitations: Renal or Urologic disease, sever
dehydration or ? Shock.
• Thank you!
The Receiver Operating Characteristic
Curve.
• true positive rate (Sensitivity) is plotted in function of the
false positive rate (100-Specificity) for different cut-off
points.
• Each point on the ROC curve represents a
sensitivity/specificity pair corresponding to a particular
decision threshold.
• A test with perfect discrimination has a ROC curve that
passes through the upper left corner (100% sensitivity,
100% specificity). Therefore the closer the ROC curve is
to the upper left corner, the higher the overall accuracy
of the test .
ROC Chart

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