Background/Purpose: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is considered a chronic relapsing condition, with unknown etiology. This study was undertaken to gain insight to the molecular processes and potential biomarkers in blood samples collected prior to the onset of symptoms

Methods: The National Patient Register and Cause of Death register were searched for AAV-ICD codes and linked to the registers of five biobanks and eighty-five AAV cases were identified (34 males, 51 females) with samples >1month< 10years from AAV symptom onset. For each case two controls matched for sex, age, and sampling date were included. Samples were analyzed using ELISAs for PR3- or MPO-ANCA specificities. Ninety-two protein markers were analyzed using Olink Inflammation panel, (OLINK, Uppsala, Sweden) with 73 eligible after quality control.

Results: Eight protein markers were significantly altered between pre-AAV and controls, with higher levels of CCL23, CXCL5 (p< 0.01-0.05) and lower levels of Flt3L, STAMBP, ADA, TNFB, CX3CL1 and IL-15RA (p< 0.01-0.05) in the pre-AAV individuals. Nine protein markers were found significantly associated with time to symptom onset; CXCL9, CD244, VEGFA, CXCL1, TNFSF9, OPG, CSF-1, IFN-gamma and CD40 (p< 0.01-0.05). In pre-AAV individuals, six proteins were associated with MPO-ANCA-positivity compared with the MPO-ANCA-negative pre-AAV individuals which showed no overlap with the seven proteins related to PR3-ANCA-positivity.

Conclusion: To our knowledge our study is the first to analyze for and identify protein markers before symptom onset in AAV. This allowed for further studies of underlying cellular and molecular mechanisms in AAV pathogenesis as well as the diversification into PR3-ANCA and MPO-ANCA subphenotypes.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/protein-profiling-in-pre-dating-samples-separate-mpo-anca-vasculitis-from-pr3-anca-vasculitis/