Journal of Molecular Medicine

, Volume 78, Issue 12, pp 703–707

Antibody recognition of amyloidogenic transthyretin variants in serum of patients with familial amyloidotic polyneuropathy

Authors

  • Joana Almeida Palha
    • Amyloid Unit, Instituto de Biologia Molecular e Celular, Rua Campo Alegre 823, 4150 Porto
  • Paulo Moreira
    • Amyloid Unit, Instituto de Biologia Molecular e Celular, Rua Campo Alegre 823, 4150 Porto
  • Anders Olofsson
    • Department of Cell and Molecular Biology, Umea University, Umea
  • Erik Lundgren
    • Department of Cell and Molecular Biology, Umea University, Umea
  • Maria João Saraiva
    • Amyloid Unit, Instituto de Biologia Molecular e Celular, Rua Campo Alegre 823, 4150 Porto
Original Article

DOI: 10.1007/s001090000163

Cite this article as:
Palha, J., Moreira, P., Olofsson, A. et al. J Mol Med (2001) 78: 703. doi:10.1007/s001090000163

Abstract

Familial amyloidotic polyneuropathy (FAP) is a late-onset inherited disease characterized by the deposition of amyloid fibrils. FAP is associated with mutations on the transthyretin (TTR) gene. A monoclonal antibody, MAb 39-44, reacting with high molecular weight aggregates of TTR but not with tetrameric TTR has recently been generated and characterized. This antibody recognizes a cryptic epitope that is expressed in isolated recombinant amyloidogenic mutants and in ex vivo amyloid. In the present work we show that this amyloid-specific antibody specifically recognizes in a direct enzyme-linked immunoassay (ELISA) plasma TTR from carriers of various mutations associated with FAP, both in asymptomatic individuals and in patients. In contrast, it does not react with plasma TTR from healthy individuals or that from carriers of nonpathogenic mutations. Using the ELISA developed in this study we identified three different TTR mutations in Portuguese patients with neuropathy of unknown cause, later shown to have amyloid tissue deposition. This antibody recognizes conformations that express cryptic epitopes shared by amyloidogenic TTR variants associated with FAP, not present among nonpathogenic TTR molecules. This antibody will contribute to further identify and characterize intermediates of the amyloidogenic cascade. In addition, it will also be useful for screening amyloidogenic TTR mutations in patients with neuropathy of unknown cause, prior to precise molecular diagnosis using protein and/or DNA analysis.

Transthyretin Familial amyloidotic polyneuropathy Neuropathies Amyloid Conformation specific antibodies

Copyright information

© Springer-Verlag 2000