Localized and systemic AL-amyloidosis: Aspects on protein structure, fibril formation and analytical methods
1998 (English)Doctoral thesis, comprehensive summary (Other academic)
AL-amyloidosis is a protein storage disease and one of the most common types of amyloidosis. The precursor protein is a monoclonal immunoglobulin light chain which originates from plasma cell dyscrasia in systemic AL-amyloidosis and is probably produced by a local plasma cell clone in localized AL-amyloidosis. Systemic AL-amyloidosis is a fatal disease, but the prognosis is improved by early diagnosis. The process leading to AL-amyloid fibril formation is not clear, but changes in the primary protein structure, associated substances and local tissue factors play a role. In order to interfere with amyloid deposition, it is necessary to understand the factors implicated in amyloid fibril formation.
In this work, biochemical and immunological methods have been used to analyze AL-proteins and other factors involved in amyloid fibril formation. Conventional analytical methods have been extended, and a new method for typing of systemic amyloidosis has been developed. With our finding of immunoglobulin light chain of subgroup ')..V as anAL-protein, it has now been shown that the subgroups Ki-N and AI-VI of immunoglobulin light chains are capable of amyloid formation. By amino acid sequence analysis of several AL-proteins, unique amino acid substitutions were found, in addition to a remarkable pattern of amino acid substitutions in pairs. In localized AL-amyloidosis, giant cells were constantly associated with the amyloid deposits, in contrast to systemic AL-amyloidosis where giant cells only occurred in some lymph nodes with a different amyloid deposition pattern. The constant region of the light chain was found as the main component in an AL-protein as frequent constituent of ALamyloid. These fragments were found in gel filtration fractions generally not expected to contain protein material. An ELISA (enzyme linked immunosorbent assay) method was developed for typing of systemic amyloidoses from amyloid material extracted from subcutaneous adipose tissue, a simple method with no risk and little discomfort for the patient. In addition, it was shown that the subcutaneous tissue is a source for material for further AL-protein studies.
Amyloid fibril formation is probably a process involving the interaction of many factors, some of which have been studied, and better understood as a result of these experiments. The interpretation of the results is discussed in the context of a multifactorial pathogenesis of AL-amyloidosis.
Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 1998. , 54 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 571
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-28620Local ID: 13776ISBN: 91-7219-057-4OAI: oai:DiVA.org:liu-28620DiVA: diva2:249431
1998-10-23, Patologens föreläsningssal, Universitetssjukhuset, Linköping, 10:45 (Swedish)
Natvig, Jakob B., Professor
Papers, included in the Ph.D. thesis, are not registered and included in the posts from 1999 and backwards.2009-10-092009-10-092012-07-27Bibliographically approved