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- Brink, M, et al.
(författare)
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PROTEIN PROFILING IN PRE-SYMPTOMATIC ANCA-ASSOCIATED VASCULITIS INDIVIDUALS.
- 2022
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Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 362-362
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare chronic relapsing condition, with unknown etiology.ObjectivesThis study was undertaken to gain insight to the molecular processes and to find potential biomarkers in blood samples collected prior to the onset of symptoms of AAV.MethodsThe National Patient Register and Cause of Death register were searched for AAV-ICD codes and linked to the registers of five biobanks. 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.ResultsEight 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.ConclusionTo 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.Disclosure of InterestsMikael Brink: None declared, Ewa Berglin: None declared, Aladdin J Mohammad Speakers bureau: Roche, Gsk, AMGEN; Vifor, Lilly, Consultant of: Roche & AMGEN, Andrey Alexeyenko: None declared, Kristina Lejon: None declared, Solbritt Rantapää Dahlqvist: None declared
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- Brink, Mikael, et al.
(författare)
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Protein Profiling in Presymptomatic Individuals Separates Myeloperoxidase-Antineutrophil Cytoplasmic Antibody and Proteinase 3-Antineutrophil Cytoplasmic Antibody Vasculitides
- 2023
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 75:6, s. 996-1006
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a chronic relapsing condition with unknown etiology. To gain insight into the 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-related International Classification of Diseases, Ninth Revision and Tenth Revision codes and linked to the registers from 5 biobanks. Eighty-five AAV patients with samples predating symptom onset of AAV were identified. For each case of AAV, 2 matched controls were included. Proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA expression levels were analyzed using enzyme-linked immunosorbent assays. Using an Olink Inflammation panel, 73 of 92 proteins were included after quality control. Data were replicated in a second cohort of 48 presymptomatic individuals and 96 controls. Results. Of the 20 proteins with the lowest P values in the original cohort, 7 were replicated in the second cohort and 5 proteins were found to be significant between the groups in a meta-analysis. Eleven different pathways were identified in network enrichment analyses and were found to be significant in both cohorts. Stratification of samples obtained <= 5 years before symptom onset showed significant levels of CCL23, vascular endothelial growth factor A, and hepatocyte growth factor, which were also increased at borderline significant levels in the replication cohort (interleukin-6 was found to be significantly increased in the replication cohort). In presymptomatic AAV patients, 6 proteins were associated with MPO-ANCA positivity, and 7 proteins were associated with PR3-ANCA positivity. Conclusion. To our knowledge, this is the first study to identify protein markers preceding symptom onset in AAV patients. These findings set the stage for further research into the underlying cellular and molecular mechanisms in the pathogenesis of AAV and the diversification of patients into PR3-ANCA+ and MPO-ANCA+ subphenotypes.
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