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Pentraxin-3 as a Marker of Disease Activity in Takayasu Arteritis

Lorenzo Dagna, MD; Fulvio Salvo, MD; Mirta Tiraboschi, MD; Enrica P. Bozzolo, MD; Stefano Franchini, MD; Claudio Doglioni, MD; Angelo A. Manfredi, MD; Elena Baldissera, MD; and Maria Grazia Sabbadini, MD
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From Vita-Salute San Raffaele University School of Medicine and San Raffaele Scientific Institute, Milano, Italy.

Acknowledgment: The authors thank Annalisa Capobianco for performing the PTX3 enzyme-linked immunosorbent assay.

Potential Conflicts of Interest: None disclosed. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-0375.

Reproducible Research Statement:Study protocol, statistical code, and data set: Available from Dr. Dagna (e-mail, lorenzo.dagna@unisr.it).

Requests for Single Reprints: Lorenzo Dagna, MD, Unit of Medicine and Clinical Immunology, San Raffaele Scientific Institute, Via Olgettina 60, I-20132 Milano, Italy; e-mail, lorenzo.dagna@unisr.it.

Current Author Addresses: Drs. Dagna, Salvo, Tiraboschi, Bozzolo, Franchini, Baldissera, and Sabbadini: Unit of Medicine and Clinical Immunology, San Raffaele Scientific Institute, Via Olgettina 60, I-20132 Milano, Italy.

Dr. Doglioni: Department of Pathology, San Raffaele Scientific Institute, Via Olgettina 58, I-20132 Milano, Italy.

Dr. Manfredi: Autoimmunity and Vascular Inflammation Unit, San Raffaele Scientific Institute, Via Olgettina 58, I-20132 Milano, Italy.

Author Contributions: Conception and design: L. Dagna, F. Salvo, E.P. Bozzolo, E. Baldissera, M.G. Sabbadini.

Analysis and interpretation of the data: L. Dagna, F. Salvo, E.P. Bozzolo, S. Franchini, C. Doglioni, A.A. Manfredi, E. Baldissera, M.G. Sabbadini.

Drafting of the article: L. Dagna, F. Salvo.

Critical revision of the article for important intellectual content: L. Dagna, S. Franchini, E. Baldissera, M.G. Sabbadini.

Final approval of the article: L. Dagna, F. Salvo, E.P. Bozzolo, S. Franchini, E. Baldissera, M.G. Sabbadini.

Provision of study materials or patients: L. Dagna, E. Baldissera, M.G. Sabbadini.

Statistical expertise: L. Dagna.

Collection and assembly of data: L. Dagna, F. Salvo, M. Tiraboschi, E.P. Bozzolo, S. Franchni, C. Doglioni, A.A. Manfredi, E. Baldissera.

Ann Intern Med. 2011;155(7):425-433. doi:10.7326/0003-4819-155-7-201110040-00005
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Background: Because pentraxin-3 (PTX3) is produced by immune and vascular cells in response to proinflammatory signals, it may be a useful biomarker for defining disease activity in patients with Takayasu arteritis.

Objective: To compare PTX3 levels in patients who have Takayasu arteritis with those in healthy and infected controls, and to compare accuracy of PTX3 levels with that of C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) for distinguishing active and inactive disease.

Design: Cross-sectional, noninterventional study conducted between September 2005 and October 2008.

Setting: Immunology and rheumatology clinic at a university hospital in Italy.

Patients: 57 consecutive patients with Takayasu arteritis and known disease activity, 57 healthy blood donor controls, and 15 patients with acute infection.

Measurements: Disease activity by clinical criteria; plasma PTX3 and CRP levels and ESR.

Results: 27 patients had active Takayasu arteritis; 30 had inactive disease. Levels of PTX3 were higher in patients with active disease (median, >2.14 ng/mL [range, 0.57 to 48.18 ng/mL]) than in those with inactive disease (median, 0.63 ng/mL [range, 0.00 to 1.64 ng/mL]) and were higher than in healthy patients (median, 0.11 ng/mL [range, 0 to 1.20 ng/mL]) or those with acute infection (median, 0.26 ng/mL [range, 0 to 0.75 ng/mL]). A plasma PTX3 level greater than 1 ng/mL was more accurate than normal thresholds of CRP or ESR for distinguishing active from inactive disease.

Limitation: The study excluded patients with unknown or equivocal disease status.

Conclusion: Plasma levels of PTX3 could help distinguish active from inactive Takayasu arteritis but should not be adopted for clinical use until the findings are confirmed in a broader spectrum of patients whose disease activity is unknown or equivocal before testing.

Primary Funding Source: None.


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Figure 2.
Plasma PTX3 levels in controls and patients with Takayasu arteritis and plasma CRP levels and ESR in patients with inactive and active Takayasu arteritis.

The solid lines indicate the median values for each group or subgroup. CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; PTX3 = pentraxin-3. A. The stars represent the PTX3 value obtained from the 5 patients with active Takayasu arteritis in whom PTX3 was measured at the time of diagnosis. B and C. The CRP level and ESR were higher in patients with active Takayasu arthritis than in those with inactive disease. D and E. No correlation was found between the plasma levels of PTX3 and CRP. Triangles represent patients with active disease; circles represent patients with inactive disease.

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Figure 3.
Receiver-operating characteristic curves for PTX3, CRP, and ESR in 57 patients with Takayasu arteritis who had unequivocal active or inactive disease.

The star indicates the data point on the receiver-operating characteristic curve that corresponds to a PTX3 value of 1 ng/mL. The areas under the receiver-operating characteristic curve are as follows: PTX3, 0.919 (95% CI, 0.847 to 0.991); ESR, 0.750 (CI, 0.623 to 0.876); CRP, 0.684 (CI, 0.582 to 0.850). CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; PTX3 = pentraxin-3.

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Figure 4.
Tissue expression of pentraxin-3.

A and C. Pentraxin-3 (PTX3) is abundant in perivascular and interstitial areas of dense lymphomonuclear infiltrate in the arterial wall specimens from patients with active Takayasu arteritis, predominantly with an extracellular localization. B and D. In inactive arteritic lesions from patients with inactive Takayasu arteritis, PTX3 reactivity was only weak and focal, mainly in perivascular regions (PTX3 immunostaining and hematoxylin counterstaining for all images; original magnification, ×200).

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