Læknablaðið : fylgirit - 01.05.1978, Qupperneq 143

Gunnar Husby, Knut Sletten, Robin F. Anders,
Jacob B. Natvig
Institute of Immunology and Rheumatology,
Rikshospitalet and Institute of Biochemistry,
University of Oslo, Norway
THE NATURE OF AMYLOID
FIBRILS ASSOCIATED WITH
RHEUMATIC DISORDERS
The amyloid fibril (3) is the unique component
of all types of amyloid substances. The ultra-
structure of the fibrils is identical in different
clinical categories of amyloidosis like primary,
myelomaassociated and secondary amyloidosis
as well as in spontaneous and experimental
amyloidosis in animals. However, recent
investigations have shown evidence that chemi-
cally entirely different classes or proteins may
make up amyloid fibrils with identical ultra-
structure. It is interesting that the chemistry
of the fibrils to a large extent follows the much
older clinical classification of amyloidosis.
Hence, it has been established that the protein
most often found as the major subunit of primary
and myelomaassociated amyloid fibrils is smaller
or larger parts of monoclonal immunoglobulin
light chains, particularly their amino-terminal,
variable part (6,11). On the other hand, the
completely different protein AA (for nomenclature,
see 2) is consistently found as a major component
of secondary amyloid fibrils (3,5,7,8,9,12,16).
The present communication is concerned with the
amyloid protein AA and a related serum protein
SAA. In addition, we also report data on another
major fibril component, the high molecular weight
or "void volume" material which seems to be
present in amyloid fibrils of both the immuno-
globulin and the protein AA type. It is concluded
that the amyloid protein AA as well as the void
volume material of amyloid fibrils are protein
components derived from connective tissue.
Materials and methods
Amyloid fibrils were prepared according to
Pras et al. (14) from the liver of a patient
T.H. with amyloidosis secondary to juvenile
rheumatoid arthritis (JRA) and from the liver
of a patient with amyloidosis associated with
ankylosing spondylitis (AS). The fibrils were
treated with 0.1 N sodium hydroxide for
immunization of rabbits and for immunodifussion
studies, and with 6 M guanidine/ 0.1 M
dithiothreitol (DTT) for fractionation by gel
filtration on Sephadex G-100 and G-25 columns
as described in details previously (8). Amyloid
fibril subfragments purified by gel filtration
were studied by amino acid composition and
sequence analyses (8,9,16,17) and by immuno-
logic tests (8,9,11).
For comparative studies tissues from corre-
sponding normal organs were subjected to exactly
the same procedures for extraction and chemical
treatment as the amyloidotic organs, and to the
same amino acid analyses and immunologic
studies.
Anti-amyloid antiserum was raised in rabbits
by immunization with NaOH-treated amyloid
fibrils (DAM) and made mono-specific for protein
AA and the amyloid void volume material
respectively by specific absorptions (8,9,11).
Fig. 1
Gel filtration of amyloid
T.H. liver. Two major
peaks are obtained: The
Vo-material, and at a
later position the amy-
loid protein AA.
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