Isolation and sequence analysis of amyloid protein AA from a patient with cystic fibrosis.
This study represents the first sequence analysis of an amyloid fibril protein from a patient with cystic fibrosis. Although chronic infections are a hallmark of cystic fibrosis, secondary amyloidosis is a rare complication, and during the past 20 years, only 16 cases of amyloidosis in patients with cystic fibrosis have been reported. We examined amyloid fibrils isolated from the spleen of a 25-year-old man who had a history of a chronic cough since infancy and a diagnosis of cystic fibrosis at age 6 years. After solubilization in 6 mol/L guanidine and purification by gel filtration, the major component of the amyloid fibrils was a homogeneous 8000 dalton protein that reacted positively with antiserum to human amyloid A (AA) protein. Complete protein sequence analysis was carried out by using the whole protein and fragments obtained by treatment of the protein with cyanogen bromide, lysyl endopeptidase, and carboxypeptidase. The protein contained 76 residues and showed minor heterogeneity when compared with other AA protein sequences. The cystic fibrosis AA protein represents a product of the SAA-specific cDNA clone now known to be the alpha-allelic form of SAA1 in which valine is present at position 52 and alanine is at position 57.
Skinner
M
M
Arthritis Center, Boston University School of Medicine, MA 02118.
Pinnette
A
A
Travis
W D
WD
Shwachman
H
H
Cohen
A S
AS
D000328:Adult; D000595:Amino Acid Sequence; D000686:Amyloidosis / Q000150:complications; D003550:Cystic Fibrosis / Q000097:blood* / Q000150:complications; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D000685:Serum Amyloid A Protein / Q000032:analysis / Q000302:isolation & purification*
D000685:Serum Amyloid A Protein