Article
Serum proteome in patients with ANCA-associated vasculitis (AAV)
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Authors
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Torsten Kubacki
- Klinik II für Innere Medizin – Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere Medizin, Uniklinik Köln, Köln
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Holger Hägele
- Klinik II für Innere Medizin – Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere Medizin, Uniklinik Köln, Köln
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Philipp Antzcak
- Zentrum für Molekulare Medizin (ZMMK), Uniklinik Köln, Köln
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Roman Müller
- Klinik II für Innere Medizin – Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere Medizin, Uniklinik Köln, Köln
| Published: | September 14, 2021 |
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Outline
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Introduction: ANCA-associated vasculitis (AAV) is the most common cause of rapid progressive glomerulonephritis (RPGN), which often leads to severe acute renal failure. To date, there are no good biomarkers that are suitable for assessing the course of disease activity and controlling therapy. The classically used, non-specific inflammation parameters CRP and BSG, haematuria and proteinuria as well as the antibody titres of the ANCAs correlate only to a limited extent with the disease activity. Mass spectrometry-based techniques for the non-selective quantification of the proteome open up new possibilities for the identification of biomarkers in such diseases. We try to identify biomarkers that correlate with disease activity by collecting serum in patients with ANCA-associated vasculitis at different points in time (initial diagnosis, after therapy initiation/remission and relapse) in a longitudinal cohort study. Through the identification of biomarkers using new techniques in patients with AAV we hope to improve disease activity monitoring and tailored individual therapy.
Methods: Longitudinal cohort study of patients with ANCA-associated vasculitis. 42 patients were included in the study. Serum samples were collected during active disease at the time of diagnosis, during induction treatment and in remission defined by BVAS. The serum samples were analyzed by LC-MS on a Q-Exactive HF-X. Analyses were performed in the statistical compute environment R.
Results: Of the 42 patients 29 were male and 13 female with a mean age of 64.2 (43-83) years. 23 and 19 patients were pANCA/MPO and cANCA/PR3 positive respectively. The mean BVAS at time of active disease was 16.9 (±5.9). 97,6% had an active renal involvement, the mean eGFR was 41.3 ml/min (±29.4).
Proteomics identified 306 proteins that were differentially expressed between remission (BVAS 0) and active disease samples. Using a network analysis we identified 9 proteins (ATRN, HP, SERPINA3, CLEC3B, C9, CRP, FGB, APOA1, GPLD1) that were associated with BVAS but not with kidney function (eGFR) while closely connected to several proteins directly associated to eGFR.
Conclusion: Besides already known inflammation markers we also identified potential new candidates that might serve as biomarkers for disease monitoring in AAV.
Disclosures: The authors declare that there is no conflict of interest.
