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Abstract Number: 1531

Comparative Proteomic Analysis of Neutrophils Between Microscopic Polyangiitis and Granulomatosis with Polyangiitis

Teisuke Uchida1, Kouhei Nagai2, Toshiyuki Sato2, Mitsumi Arito2, Nobuko Iizuka2, Manae Kurokawa2, Naoya Suematsu2, Kazuki Okamoto2, Shoichi Ozaki3 and Tomohiro Kato4, 1Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine,, Kawasaki, Japan, 2Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, Kawasaki, Japan, 3Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine, St. Marianna University School of Medicine, Kawasaki, Japan, 4Clinical Proteomics and Molecular Medicine, St. Mariannna University Graduate School of Medicine., Kawasaki, Japan

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: ANCA, Biomarkers, neutrophils and proteomics

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Session Information

Title: Vasculitis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Both microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) belong to ANCA-associated vasculitis (AAV), in which dysfunction of polymorphonuclear cells (PMN) is thought to be involved in their pathology. Clinically, it is often difficult to distinguish MPA from GPA. In this study, proteomic profiles of PMN of MPA and GPA patients and healthy controls (HC) were analyzed using two-dimensional difference gel electrophoresis (2D-DIGE), in order to know whether the profiles are useful to discriminate between AAV and HC, or MPA and GPA.

Methods: Proteins extracted from PMN obtained from 11 MPA patients, 9 GPA patients, and 10 HC were separated by 2D-DIGE. Differentially expressed protein spots were identified by MALDI-TOF MS. Then the obtained protein profiles were subjected to the multivariate data analysis by SIMCA-P+® containing principal component analysis (PCA) and orthogonal partial-least-squares-discriminate analysis (OPLS-DA).

Results: In all the 864 protein spots detected, intensity of 55 spots were found to be significantly different (p < 0.05) among the three groups by an ANOVA analysis. 31 out of the 55 spots were identified by mass spectrometry. The protein spots whose intensity as higher in MPA than in GPA included cytoskeletal proteins, while the proteins whose intensity as higher in GPA than MPA included protein inhibitors and anti-microbial proteins. The OPLS-DA analysis revealed that the expression profile of the 55 protein spots discriminated completely the AAV group from the HC group with a sufficiently high R2 (0.903) and Q2 (0.445) values, and also discriminated completely the MPA group from the GPA group with a sufficiently high R2 (0.947) and Q2 (0.626) values.

Conclusion: These results indicated that the profile of PMN proteins may be used as a biomarker that can discriminate AAV from HC, and MPA from GPA.


Disclosure:

T. Uchida,
None;

K. Nagai,
None;

T. Sato,
None;

M. Arito,
None;

N. Iizuka,
None;

M. Kurokawa,
None;

N. Suematsu,
None;

K. Okamoto,
None;

S. Ozaki,
None;

T. Kato,
None.

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