Internalisation of immunoglobulin light chains by cardiomyocytes in AL amyloidosis: what can biopsies tell us?

Bézard, Mélanie; Zaroui, Amira; Kharoubi, Mounira; Lam, France; Poullot, Elsa; Teiger, Emmanuel; Agbulut, Onnik; Damy, Thibaud; Kordeli, Ekaterini

doi:10.1080/13506129.2024.2373748

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Article1

Preprint1

Relationship

Self Cite0

Independent2

Authors

Journals

Cited by 2 publications

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Amyloid nomenclature 2024: update, novel proteins, and recommendations by the International Society of Amyloidosis (ISA) Nomenclature Committee

Buxbaum,

Eisenberg,

Fändrich

et al. 2024

Amyloid

View full text Add to dashboard Cite

Amyloid nomenclature 2024: update, novel proteins, and recommendations by the International Society of Amyloidosis (ISA) Nomenclature Committee

Buxbaum,

Eisenberg,

Fändrich

et al. 2024

Amyloid

View full text Add to dashboard Cite

A mouse model of cardiac AL amyloidosis unveils mechanisms of tissue accumulation and toxicity of amyloid fibrils

Martinez-Rivas,

Ayala,

Bender

et al. 2024

Preprint

View full text Add to dashboard Cite

AL amyloidosis is one of the most common types of systemic amyloidosis, caused by the deposition in tissues of fibrillar aggregates of abnormal immunoglobulin (Ig) light chain (LC), leading to organ dysfunction. The most frequent and severe forms affect the kidneys and heart, the latter being associated with a poor prognosis. Despite extensive efforts to decipher the mechanisms of fibril formation and their toxicity, the lack of reliable in vivo models hinders the study of the disease in its physiological context. We developped a transgenic mouse model producing high amounts of a human AL light chain (LC). While mice exceptionnaly develop spontaneous AL amyloidosis and do not exhibit organ toxicity due to the circulating amyloidogenic free LC, a single injection of amyloid fibrils, made up of the variable domain (VL) of the human LC, or soluble VL led to amyloid deposits in the heart, vessels, spleen and, to a lesser extent, in the kidney and other visceral tissues. AL fibrils in mice contain both full length and fragmented LC with a fragmentation pattern highly superposable to that of human AL fibrils from the same LC subgroup (IGLV6-57). They also develop an early cardiac dysfunction closely resembling the human disease with increased NT-proBNP,and activation of pathways involved in the extracellular matrix remodeling and fibrosis. Overall, this transgenic AL model closely reproduces human cardiac AL amyloidosis and shares with humans the biochemical composition of the deposits, arguing for a conserved mechanism of amyloid fibrils formation. It also shows that a partial degradation of the LC is likely required to initiate amyloid fibril formations. This model offers a new avenue for research on AL amyloidosis and fills an important gap for the preclinical evaluation of new therapies.

show abstract

Internalisation of immunoglobulin light chains by cardiomyocytes in AL amyloidosis: what can biopsies tell us?

Cited by 2 publications

References 35 publications

Amyloid nomenclature 2024: update, novel proteins, and recommendations by the International Society of Amyloidosis (ISA) Nomenclature Committee

Amyloid nomenclature 2024: update, novel proteins, and recommendations by the International Society of Amyloidosis (ISA) Nomenclature Committee

A mouse model of cardiac AL amyloidosis unveils mechanisms of tissue accumulation and toxicity of amyloid fibrils

Contact Info

Product

Resources

About