Quantitative proteome profiling provides evidence of an activation of the complement cascade in ATTR amyloidosis

Treitz, Christian; Gottwald, Juliane; Gericke, Eva; Meliß, Rolf Rüdiger; Axmann, Hans-Detlef; Siebert, Frank T.; Becker, Karsten; Tholey, Andreas; Röcken, Christoph

doi:10.1080/13506129.2021.2015316

Cited by 5 publications

(1 citation statement)

References 49 publications

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“…Identification of potential biomarkers in biological fluids promotes better understanding of disease onset and progression [41]. Previous studies have showcased the role of biological markers in early diagnosis of amyloid-associated disorders [29,[42][43][44][45][46]. Despite of the presence of biological markers signifying renal failure and its associated diseases [47,48], distinct diagnostic markers for renal amyloidosis has not been explored till date.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic fingerprinting for biomarker discovery in renal amyloidosis

Ghosh

Singh

Govil

et al. 2022

Preprint

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Background Minimal change disease (MCD), a glomerular disease subtype is characterised by no visible change in the glomerulus upon light microscopy except for the urinary excretion of excess proteins. The symptoms of minimal change disease and renal amyloidosis are mostly overlapping and thereby misdiagnosed. However, the possible linkage between these two disease types has not been documented. We hypothesised that amyloid formation could be one of the players promoting the pathology associated with minimal change disease, resulting in perturbations of the downstream cellular pathways. Methods One hundred glomerular diseased patients were identified in a two-year study, based on symptoms and biochemical markers. Histopathological analysis showed predominance of minimal change disease in twenty patients. Further, gold standard Congo red staining was performed in these patients to detect amyloid deposition followed by tracking its downstream effects on cellular pathways using mass-spectrometry-based untargeted approach. Results Congo red staining showed presence of amyloid deposits in eleven minimal change diseased patients. Further, plasma metabolomic fingerprinting revealed a total of fifteen biologically important metabolites altered in minimal change diseased patients having renal amyloidosis as compared to controls. Different classes of lipids, carnitines and amino acids were found to be dysregulated in these patients. Conclusion In the present study we have shown the onset of renal amyloidosis and associated pathogenesis in minimal change diseased patients. Additionally, we have identified novel altered metabolic signatures in these patients as compared to controls. This is the first study in context to the Indian population, depicting the potential of metabolomic fingerprinting to identify novel markers for early diagnosis of amyloid formation in minimal change disease, a glomerular disease type.

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Section: Discussionmentioning

confidence: 99%

Metabolomic fingerprinting for biomarker discovery in renal amyloidosis

Ghosh

Singh

Govil

et al. 2022

Preprint

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Clinical and biochemical characterization of asymptomatic carriers and symptomatic patients with hereditary transthyretin amyloidosis caused by TTR V30L mutation

Jiao,

Wang,

et al. 2024

Neurol Sci

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Cryo-EM structure of an ATTRwt amyloid fibril from systemic non-hereditary transthyretin amyloidosis

et al. 2022

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Wild type transthyretin-derived amyloid (ATTRwt) is the major component of non-hereditary transthyretin amyloidosis. Its accumulation in the heart of elderly patients is life threatening. A variety of genetic variants of transthyretin can lead to hereditary transthyretin amyloidosis, which shows different clinical symptoms, like age of onset and pattern of organ involvement. However, in the case of non-hereditary transthyretin amyloidosis ATTRwt fibril deposits are located primarily in heart tissue. In this structural study we analyzed ATTRwt amyloid fibrils from the heart of a patient with non-hereditary transthyretin amyloidosis. We present a 2.78 Å reconstructed density map of these ATTRwt fibrils using cryo electron microscopy and compare it with previously published V30M variants of ATTR fibrils extracted from heart and eye of different patients. All structures show a remarkably similar spearhead like shape in their cross section, formed by the same N- and C-terminal fragments of transthyretin with some minor differences. This demonstrates common features for ATTR fibrils despite differences in mutations and patients.

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Quantitative proteome profiling provides evidence of an activation of the complement cascade in ATTR amyloidosis

Cited by 5 publications

References 49 publications

Metabolomic fingerprinting for biomarker discovery in renal amyloidosis

Metabolomic fingerprinting for biomarker discovery in renal amyloidosis

Clinical and biochemical characterization of asymptomatic carriers and symptomatic patients with hereditary transthyretin amyloidosis caused by TTR V30L mutation

Cryo-EM structure of an ATTRwt amyloid fibril from systemic non-hereditary transthyretin amyloidosis

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