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Dialysis-related amyloid is amyloid of beta-2-microglobulin AM 2M origin.

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DiQlysis-relatedamyloid is amyloid of
bda-2-microglobulin (AMBzM)origin
To the Editor:
The recent article by Bardin et a1 (1) and, particulady, the letter by Huaux et al(2) were of interest to us. Both
groups described amyloid lesions of bone which occurred in
patients receiving long-term hemodialysis. Dr. Bardin's
group described the association of these lesions with
amyloidosis of the synovial tissues and crippling joint deformities. We have described 2 dialysis patients (3,4) with
amyloid tumors of the femoral necks and heads who presented with femoral neck fractures. These patients are very
similar to those described in the letter by Dr. Huaux and his
In an effort to further categorize this amyloid, Huaux
et al employed the potassium permanganate method (9,
which is based on the principle that amyloid of the AA type
(the material associated with cases of classic secondary
amyloidosis) loses Congo red affinity when tissue sections
are treated with potassium permanganate prior to staining.
Because the amyloid in his patients reacted ih the fashion
previously associated only with amyloid of the AA type,
Huaux and coworkers concluded that dialysis-related
amyloid was of the AA type. In January 1985, we reported
that the amyloid which we had encountered in the femoral
head specimens of 2 patients receiving long-term hemodialysis was potassium permanganate sensitive, but immunohistochemical staining for AA protein was negative (3). We
concluded, therefore, that dialysis-related amyloid was not
of the AA type, but was probably a new type of amyloid
material not previously described. Since that time, another
group has independently confirmed our observations (6).
Biochemical investigations by our group (7) and
others (8) have shown that this amyloid material is related to
beta-2-microglobulin (PzM), a component of the major
histocompatibility complex. Identification of this amyloid
material may also be accomplished by standard immunoperoxidase staining of paraffin-embedded tissue sectiods for b M , as shown in recent reports by us (9) and others
Serum P2M concentrations in the 2 patients we
described were markedly elevated, at 98.8 mg/liter and 105.8
mghiter (normal 0-4.4). Despite the marked elevation of
serum P2M in the patients with amyloid tumors of bone, we
have also shown that these levels do not significantly differ
from E M levels in patients receiving long-term hemodialysis
in whom there is no evidence of amyloid disease (1 1).
In summary, tumoral amyloidosis of bone in patients
undergoing long-term hemodialysis is a manifestation of a
new tqpe of amyloid material related to P2M. Although this
material is sensitive to potassium permanganate, it is not
related to amyloid of the AA type. To reflect that P2M is the
Arthritis and Rheumatism, Vol. 29, No. 9 (September 1986)
amyloidogenic protein of origin, we have proposed that this
entity be termed amyloidosis of the AMmMtype.
Terence T. Casey, MD
William J. Stone, MD
Carol R. DiRaimondo, MD
David L. Page, MD
Vanderbilt University
Nashville, TN
Peter D. Gorevic, MD
State University of New York at Stony Brook
Stony Brook, N Y
I . Bardin T , Kuntz D, Zingraff J , Voisin M-C, Zelmar A , Lansaman J: Synovial amyloidosis in patients uddergoing long-term
hemodialysis. Arthritis Rheum 28: 1052-1058, 1985
2. Huaux JP, Noel H, Malghem J , Maldague B, Devogelaer JP,
Nagant d e Deuxchaisnes C: Erosive azotemic osteoarthropahy:
possible role of amyloidosis (letter). Arthritis Rheum 28:
1075-1076, 1985
3. Casey TT, Stone WJ, DiRaimondo CR, DiRaimondo CV, Page
DL: Tumoral amyloidosis of bone in long term hernodialysis
patients: a new type of amyloid disease? (abstract). Lab Invest
52:13A, 1985
4. DiRaimondo CR, Casey TT, DiRaimondo CV, Stone Wj:
Pathologic fractures associated with idiopathic amyloidosis of
bone in chronic hemodialysis patients. Nephron 43:22-27, 1986
5. Wright JR, Calkins E, Humphrey RL: Potassium perrnangahate
reaction in amyloidosis. Lab Invest 36:27&281, 1977
6. Morita T, Suzuki M, Kamimbra A, Hirasawa Y:Amyloidosis of
a new type in patients on long term hemodialysis. Arch Pathol
Lab Med 109: 1029-1032, 1985
7. Gorevic PD, Casey TT, Stone WJ, DiRaimondo CR, Prelli FC,
Frangione 9: Beta-2-microglobulin is an amyloidogenic protein
in man. J Clin Invest 76:2425-2429, 1965
8. Gejyo F, Yamada T, Odani S, Nakagawa Y, Arakawa M,
Kunitomo T, Kataoka H, Suzuki M, Hirasawa Y, Shirahama T,
Cohen AS, Schmid K: A new form of amyloid protein associated with chronic hemodialysis was identified as beta 2-microglobulin. Biochem Biophys Res Commhn 129:701-706, 1985
9. Casey TT, Stone WJ, DiRaimondo CR, Brantley BD,
DiRaimondo CV, Gorevic PD, Page DL: Tumoral amyloidosis
of bone of beta-2-microglobulin origin in chronic hemodialysis
patients: a new type of amyloid diseade. Hum Pathol (in press)
10. Shiraharna T, Skinner M, Cohen AS, Gejyo F, Arakawa M,
Suzuki M, Hirasawa Y: Histochemical and immunohistochemical characterization of amyloid associated with chronic
hemodialysis as beta-2-microglobulin. Lab Invest 53:705-709,
11. DiRaimondo %R, Casey TT, Gorevic PD, DiRaimondo CV,
Stone WJ: Beta-2-microglobulin amyloidosis in chronic
hernodialysis patients (abstract). Clin Res 34:82A, 1986
Carpal tunnel syndrome and type of dialysis
membrane used in patients undergoing long-term
To the Editor:
Carpal tunnel syndrome (CTS) is being recognized
with increasing frequency in patients undergoing long-term
hemodialysis ( 1 ) . It may be related to the duration of the
dialysis therapy since it occurs in more than 50% of patients
treated in excess of 10 years. Although the etiology of CTS
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microglobulin, beta, dialysis, amyloid, origin, related
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