Splenic ellipsoids might be significant in the early development of AA amyloidosis

AA amyloidosis is a potential complication of chronic inflammation or infection, for example, rheumatoid arthritis and tuberculosis, and is characterised by systematic deposition of protein fibrils in the tissues of organs such as the spleen and liver. Similar deposition, but of other proteins, also occurs in diseases such as Alzheimer's disease, Parkinson’s disease, and prion-associated disease (“mad cow disease”).

In her thesis, Randi Sørby used experimental amyloidosis in the mink as a model to study how amyloid deposition arises in different parts of the spleen. This model was chosen because the mink has especially well-developed ellipsoids, which are lacking in the more commonly-used experimental animals such as mouse and rat, but which are found in most other mammals, including man. Studies have shown that ellipsoids are central structures in amyloid deposition and that they play an early role in the development of the disease.

In addition to amyloid fibrils, other proteins have been demonstrated (amyloid P component and apolipoproteins) and long polysaccharides (glycosaminoglycans)that may also be significant for the development of the depositions. One particularly interesting find was that several of these molecules were already present normally in the ellipsoids, which may help to explain why ellipsoids are involved so early.

The structure and general functions of ellipsoids were also studied. Sørby showed that ellipsoids also in mink are an effective filter of blood plasma. Various substances injected into the blood, such as carbon particles, small plastic spheres, and antigen-antibody complexes, were effectively removed by cells in the wall of the ellipsoids. These filtering qualities very likely play a role in he the development of the amyloid depositions.

The experimental model of amyloidosis in the mink has been further refined by injecting an extract of amyloid-containing tissue (“amyloid enhancing factor”). In this method, amyloid deposition develops significantly faster and shows a more predictable progression. This will enable future studies of the ellipsoid's role in the earliest phases of amyloidosis development.

Cand. med. vet. Randi Sørby defended her thesis for the degree of Philosophiae Doctor(PhD) on May 30, 2008, with the title “The involvement of splenic microenvironments, with emphasis on the ellipsoids, in experimental AA amyloidosis in mink.”

The work was carried out at the Department of Basic Sciences & Aquatic Medicine of the Norwegian School of Veterinary Science, and was a collaboration with Dr. med. Tale Nordbye Wien and Professor Gunnar Husby of the Rikshospitalet University Hospital HF.