Journal Article

FZJ-2026-04649

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Transthyretin stabilizer therapy increases naturally-occurring antibodies in ATTR cardiomyopathy

Settelmeier, S. ; Agranovski, D. ; Steinhardt, M. ; Waydhas, S. ; Gering, I.FZJ* ; Cejka, V. ; Morbach, C. ; Störk, S. ; Willbold, D. ; Küppers, R. ; Vogel, J. ; Michel, L. ; Carpinteiro, A. ; Reinhardt, H. C. ; Dodel, R. ; Rassaf, T. ; Ross, A. J. ; Hendgen-Cotta, U. B. (Corresponding author)

2026
Taylor & Francis Group Abingdon

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Please use a persistent id in citations: doi:10.1080/13506129.2026.2651299  doi:10.34734/FZJ-2026-04649

Abstract: Background: Amyloid transthyretin cardiomyopathy (ATT R-CM) results from extracellular deposition of misfolded transthyretin (TT R), causing progressive heart failure. Naturally-occurring antibodies (nAbs) targeting misfolded proteins exist in neurodegenerative disease, but their presence in ATT R-CM is unknown. The objective of this study is to determine whether nAbs against TT R (nAbsTT R) exist in humans and whether they are influenced by disease or its treatment.Methods: Serum from healthy donors, umbilical cord blood (UCB), and patients with ATT R-CM - both untreated and receiving TT R-stabilizing therapy - was analyzed for nAbsTT R using immunoassays, blotting, and binding studies. Functional activity was evaluated in a fibril formation assay.Results: nAbsTT R binding both native and amyloid TT R (ATT R) with high affinity (KD 30 nM/7 nM) were detected in healthy serum and UCB. NAbsTT R levels were significantly altered in ATT R-CM compared to controls: nAbsTT R (IgG) were higher while nAbsTT R (IgM) were lower. nAbsTT R of both subtypes significantly increased by 22% (p ≤ 0.05) in patients receiving TT R-stabilizing therapy. In vitro, nAbsTT R suppressed TT R fibril aggregation.Conclusions: Naturally-occurring TT R-targeting antibodies are present from birth, modulated by disease and therapy, and inhibit fibril formation. These findings reveal an unrecognized immune mechanism with potential relevance for ATT R-CM pathogenesis and treatment.

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Contributing Institute(s):

1. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)

Appears in the scientific report 2026

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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