Background/Purpose: Neutrophils play an important role in the pathogenesis of necrotizing vasculitis, and activation of neutrophil is one of important triggers of the disease process. Recent reports suggest that platelets can stimulate neutrophils directly via aggregation by these cells or indirectly via chemokines produced by platelets. Thus, we hypothesized that activation of neutrophils by platelets may contribute to the progression of vasculitis. Our aim of this study is to clarify the phenotype alteration of circulating platelets and neutrophils toward aggregation in patients with vasculitis.

Methods: Untreated patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and large vessel vasuculitis (LVV) who visited Keio University Hospital between 2015 and 2017 were consecutively involved and compared with 33 healthy controls (HC). Patients with AAV and LVV fulfilled 2012 Revisited International Chapel Hill Consensus Normenclature or American College of Rheumatology 1990 criteria. Platelet-rich plasma and neutrophils were isolated from heparinized whole blood using gradient centrifugation. Expression levels of CD62P on platelets and CD41a on neutrophils which involved in platelet-neutrophil interaction were analyzed by FACS. The correlation between expression levels of CD62P and CD41a on these cells and clinical parameters of the patients were also analyzed.

Results: Four microscopic polyangitis (MPA), 2 granulomatosis with polyangitis (GPA) as AAV, and 5 giant cell arteritis (GCA), 3 Takayasu arteritis (TAK) as LVV were involved. As of AAV, mean age was 67 ± 8 years, 62% male, mean BVAS 15 ± 2, mean neutrophil counts 6,654 ± 1,262 /μL, and mean platelet counts 34 ± 6 × 10⁴/μL. As of LVV, mean age 66 ± 4 years, 53% male, mean neutrophil counts 5,507 ± 600 /μL, and mean platelet counts 36 ± 5 × 10⁴/μL. The treatment was started with 1 mg/kg/day of prednisolone for all patients. Proportion of CD62P⁺ platelets was remarkably higher in AAV (2.5 ± 0.09 versus 1.7 ± 1.0, p = 0.05) and LVV (3.2 ± 1.1 versus 1.7 ± 1.0, p = 0.005) compared with HC. Moreover, proportion of CD62P⁺ platelets was tended to be decreased by immunosuppressive treatment (2.6 ± 0.7 versus 2.0 ± 0.6, p = 0.1) along with improvement of disease activity. In addition, proportion of CD41a⁺ neutrophils also tended to be higher in AAV and LVV compared with HC (27 ± 8.8 versus 20 ± 5.8, p = 0.07), and decreased by the treatment (29 ± 9.2 versus 18 ± 6.8, p = 0.07). Interestingly, proportion of CD41a⁺ neutrophils was significantly and positively correlated with CD62P⁺ platelets (r² = 0.8, p = 0.04) and ANCA titer (r² = 0.9, p = 0.003) in AAV patients.

Conclusion: Phenotype of circulating platelets and neutrophils are altered toward cell to cell contact and associate with disease activity. These results suggest that platelet-neutrophil interaction is involved in the disease process of vasculitis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/altered-phenotype-of-platelets-and-neutrophils-toward-neutrophil-platelet-interaction-in-circulation-of-small-and-large-vessel-vasuculitis/