235. Protein profiling to identify biomarkers for disease activity in ANCA-associated vasculitis
Creators: name: Hellbacher1, Erik
name: Van Hoef2, Vincent
name: Knight1, Ann
name: Gunnarsson3, Iva
name: Bruchfeld4, Annette
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background:</strong> To differentiate between a relapse with increased inflammatory activity and lasting effects of permanent organ damage caused by previous inflammation is a common difficulty in the follow-up of patients with ANCA-associated vasculitis (AAV). Few clinical or molecular biomarkers have been identified and validated to differentiate between these two states.In order to improve clinical diagnostics of patients with AAV, we aimed to identify reliable and easily measurable protein biomarkers of active inflammation in PR3- and MPO-ANCA positive (+) AAV. <strong>Methods:</strong> Plasma samples were collected from patients with AAV with active inflammation and no/ minimal ongoing immunosuppression (n = 69), from patients with AAV in remission (n = 45; Birmingham vasculitis activity score = 0, under treatment), disease controls with active inflammation in SLE (n= 15) and RA (n = 31) and healthy controls (n = 138) at six Swedish rheumatological and/or nephrological centers. All AAV patients were classified into granulomatosis with polyangiitis or microscopic polyangiitis according to the European Medicines Agency algorithm. Data concerning age at inclusion, presence of ANCA and creatinine levels were collected from medical records. Samples were analyzed for the relative levels of 181 proteins associated with inflammation and/or cardiovascular disease, using proximity extension assay (OLINK protein panels). Differential protein expression between groups was analyzed using ANOVA, with age and glomerular filtration rate (CKD-EPI) as covariates and Tukey adjusted P value threshold, and partial least square discriminant analysis (PLS-DA). <strong>Results:</strong> In univariate analyses, sets of proteins with levels significantly differentiating from those of healthy controls, were identified for patients with active PR3- and MPO-ANCA+ AAV, respectively. Patients with active PR3/MPO-ANCA+ AAV, SLE and RA showed distinct protein profiles in comparison with healthy controls, and in between the different patient groups. Importantly, the protein profiles differed between PR3- and MPO-ANCA+ patients. Next, protein levels were compared between AAV patients with active disease and patients in remission, divided according to ANCA, revealing significant differences in proteins levels, partially overlapping differences identified in comparison with healthy controls. Comparison between patients with active PR3-ANCA+ AAV and MPO-ANCA+ AAV identified 11 proteins with significantly different levels. PLS-DA multivariate analyses confirmed key proteins within the protein sets that separated the groups, including separation between PR3- and MPO-ANCA+ AAV (Figure 1). <strong>Conclusions:</strong> We conclude that altered plasma protein expression in patients with active inflammatory AAV distinguish these individuals from patients in remission, patients with other autoimmune diseases and healthy controls and that analysis of selected proteins may facilitate clinical evaluation of patients’ disease state. Differential protein profiles between PR3- and MPO-ANCA+ AAV patients confirm previous indications of different pathophysiology behind these subgroups. <strong>Disclosures:</strong> None.