226. Annexin A1 in anti-neutrophil cytoplasmic antibody-mediated vasculitis: a potential biomarker
Creators: name: Joop Aendekerk1, 2
name: Renée Ysermans1, 2
name: Matthias Busch1, 2
name: Amiral3, Jean
name: Reutelingsperger2, Chris
name: Pieter van Paassen1, 2
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background:</strong> In anti-neutrophil cytoplasmic antibody-mediated vasculitis (AAV), uncontrolled systemic inflammation is present with a prominent role for neutrophils. Annexin A1 (AnxA1) is increased by neutrophil-mediated inflammation and plays an important role by reducing neutrophil infiltration and inducing neutrophil apoptosis. Proteomic analysis in AAV patients shows a dysregulation in AnxA1, sustaining a pro-inflammatory state. We hypothesized AnxA1 levels are increased during active AAV reflecting (neutrophil-mediated) inflammation. Furthermore, we hypothesized AnxA1 decreases in response to the dampening effect on inflammation by initiating immunosuppressive therapy. To test these hypotheses, we assessed serum AnxA1 levels in a prospective longitudinal AAV cohort and healthy control patients. <strong>Methods: </strong>Patients (<em>n</em>=72) were included from the PROMAVAS study, i.e., a prospective longitudinal study including patients presenting with active AAV at Maastricht UMC, between April 2019 and June 2021. Clinical outcome data were obtained from the PROMAVAS clinical database. Longitudinal serum samples were obtained at the time of active disease (<em>n</em>=72), and 6 weeks (<em>n</em>=61) and 6 months (<em>n</em>=61) after initiating therapy. Disease activity was scored using the BVAS. Consenting healthy donors (HC) were recruited to assess normal serum AnxA1 levels. Serum AnxA1 levels, determined by an AnxA1 specific ELISA, are expressed in ng/ml and presented as median [IQR]. Based on the healthy control cohort (<em>n</em>=61) the normal range for AnxA1 was set to 0-34 ng/ml. <strong>Results: </strong>Seventy-two active AAV patients were included with a mean age of 63 (±13) years and a M:F ratio of 1.8. PR3-, MPO-ANCA or both were detected in 38 (53%), 33 (46%) and 1 (1%), respectively. Renal (<em>n</em>=41; 59%) and pulmonary (<em>n</em>=33; 47%) involvement were the predominant organs affected. All patients were treated with immunosuppressive therapy (i.e., corticosteroids with either Rituximab [<em>n</em>=43; 60%], cyclophosphamide [<em>n</em>=16; 22%] or both [<em>n</em>=13; 18%]). At 6 months 68 (96%) patients were in remission according to a BVAS of 0. Death occurred in 5 (7%) patients. AAV patients showed higher median levels of AnxA1 compared to HC (38 [24-154] vs. 16 [11-24], respectively, Figure 1, Mann-Whitney U test, <em>P</em>&lt;0.0001). At presentation 38 (53%) AAV patients had AnxA1 levels above the cut-off value. This number decreased to 16 (26%) and 10 (16%) at 6 weeks and 6 months, respectively, after initiating therapy. AnxA1 levels at presentation, week 6 and month 6 reduced from 38 [24-154] to 20 [12-35] and 15 [8-30] (ng/ml, Figure 1, Wilcoxon-signed rank, <em>P</em>&lt;0.001) respectively. Interestingly, in contrast to active disease, at month 6 AnxA1 levels did not differ from healthy control levels (Figure 1, <em>P</em>=0.76). AnxA1 levels did not correlate with CRP. AnxA1 levels did not differ between sex, ANCA specificity, renal or pulmonary involvement. <strong>Conclusions: </strong>Serum AnxA1 levels were increased in active AAV patients compared to healthy controls. Furthermore, AnxA1 levels decrease after initiation of immunosuppressive therapy. These results indicate that serum AnxA1 can be helpful in recognizing active AAV and beneficial in assessing treatment response. Further studies are warranted to decipher the role of AnxA1 in dampening inflammation and fibrosis formation in AAV. <strong>Disclosure: </strong>none <strong>Figure 1. </strong>AnxA1 levels (ng/ml) during active AAV were significantly higher than healthy controls (HC). Levels decreased significantly after initiating immunosuppressive therapy at week 6 and remained low at month 6. At month 6, AAV serum did not differ from HC serum. AnxA1 levels were compared using Mann-Whitney U test (red) and Wilcoxon signed rank test (blue). ns, not significant; *** P&lt;0.0001