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A father and his son with systemic AL amyloidosis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology. (Amyloid)
Department of Hematology, Sahlgrenska University Hospital, Gothenburg.
Department of Pathology, Sahlgrenska University Hospital, Gothenburg.
Biotechnology Center of Oslo, University of Oslo, Norway.
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2009 (English)In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 94, no 3, 437-439 p.Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
2009. Vol. 94, no 3, 437-439 p.
Keyword [en]
amyloid, immunoglobulin light chain
National Category
Cell and Molecular Biology
Research subject
Pathology
Identifiers
URN: urn:nbn:se:uu:diva-100205DOI: 10.3324/haematol.13640ISI: 000263922600025PubMedID: 19176364OAI: oai:DiVA.org:uu-100205DiVA: diva2:209971
Available from: 2009-03-29 Created: 2009-03-26 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Influence of Genes and Post-translational Modifications in the Pathogenesis of Light Chain Amyloidosis
Open this publication in new window or tab >>Influence of Genes and Post-translational Modifications in the Pathogenesis of Light Chain Amyloidosis
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Amyloid is formed when a normally soluble protein undergoes conformational changes that results in self-aggregation. The pathogenic protein in light chain amyloidosis is an immunoglobulin light chain produced by a plasma cell clone mainly in the bone marrow. The light chain is transported via the circulation to various organs and tissues but deposits only in certain locations. The disease is very heterogenous and every patient can be considered to have their own disease, since symptoms and outcome vary enormously. In this thesis I have tried to elucidate some factors involved in the pathogenesis of light chain amyloidosis.

Firstly, we investigated the impact of the germ line origin for tissue affinity and found out that even though it is important other factors like posttranslational modifications are also of relevance.

Secondly we describe familial-like light chain amyloidosis in Sweden, affecting a father and son. The inheritance is hard to explain but we believe that genetic factors that might be involved in the rearrangement of light chain genes or that familial immunopathies predispose certain families for development of light chain amyloidosis.

Thirdly, we wanted to study if cleavage of the light chain occurs before or after deposition, since purified light chain amyloid contains full-length, and N- and C-terminal fragments of the protein. The cleavage pattern in 1-5 organs from 6 patients was analyzed by Western blot with three antisera directed against one epitope in the N-terminal and two epitopes in the N- and C-terminal part of the protein. By using these antisera we could determine to which part of the light chain molecule the fragment belonged. We found fragments that could be aligned to compose the whole light chain. The finding indicates that cleavage occurs after deposition.

Finally, we wanted to investigate if lambda amyloid fibrils contain small C-terminal fragments from the constant domain, earlier been detected in patients with kappa light chain amyloidosis. In concordance, we identified the same fragments in lambda patients and could demonstrate that these fragments made fibrils in vitro. The role of the small C-terminal peptides for the development of light chain amyloidosis must be further investigated.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 51 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 455
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:uu:diva-100899 (URN)978-91-554-7514-7 (ISBN)
Public defence
2009-05-20, Fåhreussalen, Dag Hammarskjöldsväg 20 , Uppsala, 09:00 (English)
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Supervisors
Available from: 2009-04-28 Created: 2009-04-10 Last updated: 2009-04-30Bibliographically approved

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Enqvist, StinaWestermark, Per

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