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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ACR Meeting Abstracts - https://acrabstracts.org/abstract/comparative-proteomic-analysis-of-neutrophils-between-microscopic-polyangiitis-and-granulomatosis-with-polyangiitis/