| Autor: |
Mikael, Brink, Ewa, Berglin, Aladdin J, Mohammad, Anders, Lundquist, Inger, Gjertsson, Andrey, Alexeyenko, Kristina, Lejon, Solbritt, Rantapää-Dahlqvist |
| Rok vydání: |
2022 |
| Zdroj: |
Arthritisrheumatology (Hoboken, N.J.). |
| ISSN: |
2326-5205 |
| Popis: |
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a chronic relapsing condition with unknown etiology. To gain insight into molecular processes underlying the disease, we examined biomarkers in blood samples collected prior to symptom onset. Methods The National Patient Register and Cause of Death register were searched for AAV-ICD-codes and linked to the registers from five biobanks. Eighty-five AAV-cases with samples predating symptom onset of AAV were identified. For each case two matched controls were included. Proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA were analyzed using enzyme-linked immunosorbent assays. Using Olink Inflammation panel, we included 73 of 92 proteins after quality control. Data was replicated in a second cohort of 48 pre-symptomatic cases and 96 controls.Of the 20 proteins with the lowest p-value in the original cohort seven were replicated in the second cohort and in a meta-analysis five were significant between the groups. Eleven different pathways were identified in network enrichment analyses and were significant in both cohorts. Stratification of samples obtained ≤5 years before onset showed significant levels of CCL23, VEGF-A, HGF and borderline in the replication cohort besides IL-6. In pre-AAV cases, six proteins were associated with MPO-ANCA+, and seven proteins with PR3-ANCA+.To our knowledge, this is the first study to identify protein markers preceding symptom onset in AAV. These findings set the stage for further research into underlying cellular and molecular mechanisms in AAV pathogenesis and the diversification into the PR3-ANCA and MPO-ANCA sub-phenotypes. This article is protected by copyright. All rights reserved. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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