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Urine proteomics for discovery of improved diagnostic markers of Kawasaki disease.

Kentsis A, Shulman A, Ahmed S, Brennan E, Monuteaux MC, Lee YH, Lipsett S, Paulo JA, Dedeoglu F, Fuhlbrigge R, Bachur R, Bradwin G, Arditi M, Sundel RP, Newburger JW, Steen H, Kim S - EMBO Mol Med (2012)

Bottom Line: We discovered that urine proteomes of patients with KD, but not those with mimicking conditions, were enriched for markers of cellular injury such as filamin and talin, immune regulators such as complement regulator CSMD3, immune pattern recognition receptor muclin, and immune cytokine protease meprin A.Significant elevations of filamin C and meprin A were detected in both the serum and urine in two independent cohorts of patients with KD, comprised of a total of 236 patients.Notably, meprin A was enriched in the coronary artery lesions of a mouse model of KD.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology/Oncology, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

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Urine filamin C and meprin A correlate with disease activity in patients with KDA,B. Urine meprin A (A) and filamin C (B) levels in five patients with KD, as measured in matched specimens collected at diagnosis, 24–48 h after treatment, and 1 month after complete clinical response.C. Urine meprin A level in one patient who experienced recurrence of KD 5.5 months after initial presentation.D. Scatter plot showing urine filamin C levels in patients who responded to initial therapy (red, responders) versus those who required repeat treatment (green, non-responders). p = 0.0015.
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fig03: Urine filamin C and meprin A correlate with disease activity in patients with KDA,B. Urine meprin A (A) and filamin C (B) levels in five patients with KD, as measured in matched specimens collected at diagnosis, 24–48 h after treatment, and 1 month after complete clinical response.C. Urine meprin A level in one patient who experienced recurrence of KD 5.5 months after initial presentation.D. Scatter plot showing urine filamin C levels in patients who responded to initial therapy (red, responders) versus those who required repeat treatment (green, non-responders). p = 0.0015.

Mentions: In addition, we assessed the relationship between meprin A and filamin C and response to therapy, by measuring their urine concentrations in matched serial specimens. These were collected at diagnosis prior to initiation of therapy, 24–48 h after treatment with high dose aspirin and intravenous gammaglobulin, and 1 month after complete clinical response to treatment in five patients for whom matched specimens could be collected. In all patients studied, urine meprin A and filamin C levels correlated with response to treatment (one-way ANOVA p = 0.043 and 0.031, respectively, Fig 3A and B).


Urine proteomics for discovery of improved diagnostic markers of Kawasaki disease.

Kentsis A, Shulman A, Ahmed S, Brennan E, Monuteaux MC, Lee YH, Lipsett S, Paulo JA, Dedeoglu F, Fuhlbrigge R, Bachur R, Bradwin G, Arditi M, Sundel RP, Newburger JW, Steen H, Kim S - EMBO Mol Med (2012)

Urine filamin C and meprin A correlate with disease activity in patients with KDA,B. Urine meprin A (A) and filamin C (B) levels in five patients with KD, as measured in matched specimens collected at diagnosis, 24–48 h after treatment, and 1 month after complete clinical response.C. Urine meprin A level in one patient who experienced recurrence of KD 5.5 months after initial presentation.D. Scatter plot showing urine filamin C levels in patients who responded to initial therapy (red, responders) versus those who required repeat treatment (green, non-responders). p = 0.0015.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569638&req=5

fig03: Urine filamin C and meprin A correlate with disease activity in patients with KDA,B. Urine meprin A (A) and filamin C (B) levels in five patients with KD, as measured in matched specimens collected at diagnosis, 24–48 h after treatment, and 1 month after complete clinical response.C. Urine meprin A level in one patient who experienced recurrence of KD 5.5 months after initial presentation.D. Scatter plot showing urine filamin C levels in patients who responded to initial therapy (red, responders) versus those who required repeat treatment (green, non-responders). p = 0.0015.
Mentions: In addition, we assessed the relationship between meprin A and filamin C and response to therapy, by measuring their urine concentrations in matched serial specimens. These were collected at diagnosis prior to initiation of therapy, 24–48 h after treatment with high dose aspirin and intravenous gammaglobulin, and 1 month after complete clinical response to treatment in five patients for whom matched specimens could be collected. In all patients studied, urine meprin A and filamin C levels correlated with response to treatment (one-way ANOVA p = 0.043 and 0.031, respectively, Fig 3A and B).

Bottom Line: We discovered that urine proteomes of patients with KD, but not those with mimicking conditions, were enriched for markers of cellular injury such as filamin and talin, immune regulators such as complement regulator CSMD3, immune pattern recognition receptor muclin, and immune cytokine protease meprin A.Significant elevations of filamin C and meprin A were detected in both the serum and urine in two independent cohorts of patients with KD, comprised of a total of 236 patients.Notably, meprin A was enriched in the coronary artery lesions of a mouse model of KD.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology/Oncology, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Show MeSH
Related in: MedlinePlus