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Protein Profiling i...
Protein Profiling in Presymptomatic Individuals Separates Myeloperoxidase-Antineutrophil Cytoplasmic Antibody and Proteinase 3-Antineutrophil Cytoplasmic Antibody Vasculitides
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- Brink, Mikael (author)
- Umeå University,Umeå universitet,Reumatologi
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- Berglin, Ewa, MD, PhD, 1955- (author)
- Umeå University,Umeå universitet,Reumatologi
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- Mohammad, Aladdin J. (author)
- Lund University,Lunds universitet,Reumatologi och molekylär skelettbiologi,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lund OsteoArthritis Division - Clinical Epidemiology Unit,Forskargrupper vid Lunds universitet,Lund Vasculitis Epidemiology Research Group,Rheumatology,Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups,University of Cambridge
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- Lundquist, Anders, 1978- (author)
- Umeå University,Umeå universitet,Statistik
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- Gjertsson, Inger, 1962 (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research,Department of Rheumatology and Inflammation Research, Gothenburg University, Gothenburg, Sweden
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- Alexeyenko, A. (author)
- Karolinska Institute
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- Lejon, Kristina, 1967- (author)
- Umeå University,Umeå universitet,Institutionen för klinisk mikrobiologi
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- Rantapää-Dahlqvist, Solbritt (author)
- Umeå University,Umeå universitet,Reumatologi
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(creator_code:org_t)
- 2022-12-19
- 2023
- English.
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In: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 75:6, s. 996-1006
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- endothelial growth-factor
- flt3 ligand
- chemokines
- Rheumatology
Publication and Content Type
- ref (subject category)
- art (subject category)
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