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A systemic apolipoprotein A-IV-associated amyloidosis confirmed by proteome analysis

Abstract

Amyloidosis is induced by extracellular deposition of certain proteins. Thirty-six proteins have so far been identified as amyloidogenic proteins in humans. Although it is very important to determine the specific amyloid protein type for the choice of therapy for amyloidosis patient, it might be difficult to identify specific proteins from amyloid-deposited tissue. Apolipoprotein A-IV is known as an amyloid-associated protein, but there have been few reports of apolipoprotein A-IV amyloidosis. Here we report a case of systemic apolipoprotein A-IV-associated amyloidosis that was confirmed by proteome analysis using formalin-fixed paraffin-embedded tissue and an immunohistochemical technique.

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Abbreviations

AA:

amyloid A

AL:

amyloid light chain

AMI:

acute myocardial infarction

ApoAI:

apolipoprotein A-I

ApoAIV:

apolipoprotein A-IV

ApoCI:

apolipoprotein C-I

ApoCIII:

apolipoprotein C-III

ApoE:

apolipoprotein E

ATTR:

amyloid transthyretin

CKD:

chronic kidney disease

ECG:

electrocardiogram

FFPE:

formalin-fixed paraffin-embedded

Ig:

immunoglobulin

IHC:

immunohistochemistry

KDIGO:

Kidney Disease: Improving Global Outcomes

OMI:

old myocardial infarction

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Acknowledgements

The authors would like to thank Y. Kawami for the technical assistance with the experiments.

Funding

Japan Society for the Promotion of Science, Grant/Award Number: JP19K16561 (T.A.), JP20K16196 (K.T.), and the Kurozumi Medical Foundation (A.T.)

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Authors and Affiliations

Authors

Contributions

The authors contributed in the following ways: AT: conceived the study, supervised all experiments, and performed the final revision of the manuscript; TM, AT, AM, TA: performed immunohistochemical experiments; TM, AT, AM, KuT, TA: performed and analyzed proteomics experiments; YI, HI, KMu, KoT: provided the clinical data and tissue samples; TM, AT: drafted the paper; AT, KMa, YO: analyzed immunohistochemistry; TM, KuT: performed genomic sequencing; DK: performed the statistical analysis; YI, HI, KMu, KoT, MM: contributed to the interpretation of the results. MO: supervised experiments, and helped with writing the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Akira Takasawa.

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Ethics committee approval

This study was approved by the Institutional Review Board of Sapporo Medical University (IRB study number: 312-214).

Conflict of interest

The authors declare no competing interests.

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The following are the supplementary material data related to this article: Supplementary material Fig. 1 and 2, and Supplementary material Table 1, 2 and 3.

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Murakami, T., Takasawa, A., Moriki, A. et al. A systemic apolipoprotein A-IV-associated amyloidosis confirmed by proteome analysis. Virchows Arch 479, 1041–1046 (2021). https://doi.org/10.1007/s00428-021-03073-x

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  • DOI: https://doi.org/10.1007/s00428-021-03073-x

Keywords

  • Amyloidosis
  • Apolipoprotein A-IV
  • Proteome analysis
  • Formalin-fixed paraffin-embedded tissue