Diagnostic performance of amyloid A protein quantification in fat tissue of patients with clinical AA amyloidosis.
OBJECTIVE
Amyloid A protein quantification in fat tissue is a new immunochemical method for detecting AA amyloidosis, a rare but serious disease. The objective was to assess diagnostic performance in clinical AA amyloidosis.


METHODS
Abdominal subcutaneous fat tissue of patients with AA amyloidosis was studied at the start of an international clinical trial with eprodisate (NC-503; 1,3-propanedisulfonate; Kiacta), an antiamyloid compound. All patients had renal findings, i.e. proteinuria (> or =1 g/day) or reduced creatinine clearance (20 - 60 ml/min). Controls were patients with other types of amyloidosis and arthritic patients without amyloidosis. Amyloid A protein was quantified by ELISA using monoclonal antihuman serum amyloid A antibodies. Congo red stained slides were scored by light microscopy in a semiquantitative way (0 to 4+).


RESULTS
Ample fat tissue (>50 mg) was available for analysis in 154 of 183 patients with AA amyloidosis and in 354 controls. The sensitivity of amyloid A protein quantification for detection of AA amyloidosis (>11.6 ng/mg fat tissue) was 84% (95% CI: 77 - 89%) and specificity 99% (95% CI: 98 - 100%). Amyloid A protein quantification and semiquantitative Congo red scoring were concordant. Men had lower amyloid A protein values than women (p < 0.0001) and patients with familial Mediterranean fever had lower values than patients with arthritis (p < 0.001) or other inflammatory diseases (p < 0.01).


CONCLUSIONS
Amyloid A protein quantification in fat tissue is a sensitive and specific method for detection of clinical AA amyloidosis. Advantages are independence from staining quality and observer experience, direct confirmation of amyloid AA type, and potential for quantitative monitoring of tissue amyloid over time.
Hazenberg
Bouke P C
BP
Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. b.p.c.hazenberg@int.umcg.nl
Bijzet
Johan
J
Limburg
Pieter C
PC
Skinner
Martha
M
Hawkins
Philip N
PN
Butrimiene
Irena
I
Livneh
Avi
A
Lesnyak
Olga
O
Nasonov
Evgeney L
EL
Filipowicz-Sosnowska
Anna
A
Gül
Ahmet
A
Merlini
Giampaolo
G
Wiland
Piotr
P
Ozdogan
Huri
H
Gorevic
Peter D
PD
Maïz
Hédi Ben
HB
Benson
Merrill D
MD
Direskeneli
Haner
H
Kaarela
Kalevi
K
Garceau
Denis
D
Hauck
Wendy
W
Van Rijswijk
Martin H
MH
D050153:Abdominal Fat / Q000737:chemistry*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000145:classification / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism*; D016022:Case-Control Studies; D003224:Congo Red; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011407:Propane / Q000031:analogs & derivatives / Q000627:therapeutic use; D000685:Serum Amyloid A Protein / Q000032:analysis*; D013451:Sulfonic Acids / Q000627:therapeutic use
D000685:Serum Amyloid A Protein; D013451:Sulfonic Acids; D003224:Congo Red; C520274:eprodisate; D011407:Propane