Amino Acid Sequence Composition of AA Amyloid Fibrils in Cystic Fibrosis
Amyloidosis is a relatively rare complication of cystic fibrosis although chronic infections are a hallmark of the disease. During the past 20 years, sixteen cases of amyloidosis in patients with cystic fibrosis have been reported. The mean age at the time of the diagnosis of amyloid was 20 years with a range from 6-33 years.
We examined amyloid fibrils isolated from the spleen of a 25 year old male with a history of a chronic cough since infancy and a diagnosis of cystic fibrosis at age 6. Amyloid fibrils were purified by gel filtration on Sephadex G-100 in 4M guanidine, IN acetic acid. The most retarded fraction revealed a homogeneous 8000 dalton protein on polyacrylamide gel. Protein sequence analysis was carried out on the whole protein, and fragments digested with cyanogen bromide, lysyl endopeptidase, and carboxypeptidase.
This represents the first sequence analysis of AA amyloid from a patient with cystic fibrosis. The amyloid protein contained 76 residues and when compared to known AA sequences was most nearly identical to the sequence of the amyloid protein obtained from patients with juvenile rheumatoid arthritis or rheumatoid arthritis. This sequence suggests that the amyloid protein is the gene product of SAA 1 alpha.
KeywordsCystic Fibrosis Amyloid Fibril Juvenile Rheumatoid Arthritis Amyloid Protein Cyanogen Bromide
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- 1.H.P. Missmahl. Clinic, Therapie, prognose: Fortschr Med 85:621–623 (1967).Google Scholar
- 2.S.C. Ristow, J.J. Condemi, I.D. Stuard, R.H. Schwartz, M.F. Bryson. Systemic amyloidosis in cystic fibrosis. Am. J. Dis. Children 131:886–888 (1977).Google Scholar
- 3.J. Vilaseca, J. Cuevas, M. Fresno, J. Fox, J. Guardia, R. Bacardi. Systemic amyloidosis in cistic fibrosis. Am. J. Dis. Child 135:667 (1981).Google Scholar
- 5.S.J. Carretero, J.M. Fernandez, M.F. del Campo, G.J. Arenos, P.A. Rodrigo. Una rara asociacion: Fibrosis guistica y amiloidosis sistemicaGoogle Scholar
- 6.M. Biberstein, P. Wolf, B. Pettross, D. Fanestil, M. Vasquez. Amyloidosis complicating cystic fibrosis Am. J. Clin Path 80:752–754 (1983).Google Scholar
- 8.H. Michalsen, O.T. Storrosten, CF. Lindboe. Generalized amyloidosis in cystic fibrosis. Eur. J. Respir. Dis. 66:306–309 (1985).Google Scholar
- 9.R. Castile, H. Shwachman, W. Jarvis, C.A. Hadley, W. Warwick, H.P. Missmahl. Amyloidosis as a complication of cystic fibrosis. Am J. Dis. Children. 139:728–732 (1985).Google Scholar
- 10.W.D. Travis, R. Castile, G. Vawter, H. Shwachman, W. Warwick, B.A. Burke, and M. Skinner. Secondary (AA) amyloidosis in cystic fibrosis: a report of three cases. Am. J. Clin Path 85:419–424 (1986).Google Scholar
- 12.M. Skinner, T. Shirahama, A.S. Cohen, and C.L. Deal. The association of amyloid P-component (AP) with the amyloid fibril: an updated method for amyloid fibril isolation. Prep. Biochem 12:461–476 (1983).Google Scholar