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Comparative proteomic analysis of neutrophils from patients with microscopic polyangiitis and granulomatosis with
Teisuke Uchida1, Kouhei Nagai, Toshiyuki Sato
1Clinical Proteomics and Molecular Medicine, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki-shi, Kanagawa-ken, Japan.
Abstract:
Both microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) belong to ANCA-associated vasculitis (AAV), in which neutrophils play a key role in their pathology. In this study, in order to discriminate between MPA and GPA, protein profiles of peripheral blood polymorphonuclear cells (PMNs) of 11 MPA patients and 9 GPA patients and 10 healthy controls (HC) were analyzed by 2D-DIGE. In all the 864 spots detected, intensity of 55 spots was significantly different (p<0.05) among the three groups by ANOVA. 31 out of the 55 spots were identified by mass spectrometry. Orthogonal partial-least-squares-discriminate analysis revealed that the abundance profile of the protein spots discriminated the AAV group from the HC group, and the MPA group from the GPA group completely. 13 protein spots were considered as biomarker candidates to distinguish between MPA and GPA. In those, spots whose intensity was higher in MPA than in GPA included actin with various pI values, while a considerable part of spots whose intensity was higher in GPA were proteins related with the activity of neutrophils. Among the candidate proteins, ROC analysis showed that a combination of neutrophil gelatinase-associated lipocalin and a-kinase anchor protein 7 isoforms beta had a high diagnostic potential.
Biological Significance:
In this study, protein profiles of polymorphonuclear cells (PMNs) of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) patients and healthy controls (HC) were investigated by 2D-DIGE, and MS analysis. As a result, we found that the protein profiles of PMNs were useful for distinguishing between patients (MPA and GPA) and HC, and between patients with MPA and patients with GPA. Especially, we found that the 13 protein spots that consisted of 10 proteins considerably contributed to the discrimination between MPA and GPA. This is the first to demonstrate that protein profiles of PMNs are different among MPA, GPA and healthy control. The 10 proteins we identified in this study would be new biomarkers for the diagnosis of the diseases, and may be reflect the pathology difference between MPA and GPA.
Insights
This study analyzed neutrophil protein profiles to differentiate microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Distinct protein patterns in neutrophils can help diagnose these ANCA-associated vasculitis conditions.
Area of Science:
- Immunology and Proteomics
- Biomarker Discovery in Vasculitis
Background:
- Microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are types of ANCA-associated vasculitis (AAV).
- Neutrophils play a critical role in the pathology of AAV, but distinguishing between MPA and GPA can be challenging.
Purpose of the Study:
- To investigate protein profiles of polymorphonuclear cells (PMNs) to discriminate between MPA, GPA, and healthy controls (HC).
- To identify potential protein biomarkers for distinguishing MPA from GPA.
Main Methods:
- Analysis of protein profiles in peripheral blood PMNs from 11 MPA patients, 9 GPA patients, and 10 HC using 2D-DIGE.
- Identification of differentially expressed protein spots using mass spectrometry.
- Statistical analysis including ANOVA, orthogonal partial-least-squares-discriminate analysis, and ROC analysis.
Main Results:
- Significant differences in protein spot intensities were observed among MPA, GPA, and HC groups.
- Protein profiles successfully discriminated AAV patients from HC, and MPA patients from GPA patients.
- 13 protein spots, representing 10 distinct proteins, were identified as potential biomarkers differentiating MPA and GPA.
Conclusions:
- PMN protein profiles are valuable for distinguishing between MPA, GPA, and healthy individuals.
- The identified 10 proteins represent novel biomarkers for diagnosing MPA and GPA.
- These protein differences may reflect underlying distinct pathophysiological mechanisms in MPA versus GPA.
