Cross-linked elastin and collagen degradation products in the urine of patients with scleroderma.
OBJECTIVE
To measure the urinary excretion of specific cross-link amino acid markers for mature elastin (desmosine [DES] and isodesmosine [IDES]) and fibrillar collagen (hydroxylysylpyridinoline [HP] and lysylpyridinoline [LP]) in systemic sclerosis (SSc) patients and healthy controls.


METHODS
Urine specimens from 20 patients with SSc and 22 controls were assessed for DES, IDES, HP, and LP using high performance liquid chromatography and ultraviolet absorption spectroscopy, in combination with an isotope dilution technique in which the urine specimen was spiked with isotopically labeled cross-link amino acids.


RESULTS
Mean +/- SD levels of urinary DES and IDES were elevated in SSc patients by 2-3-fold, and urinary HP and LP by 3-4-fold, compared with controls (DES 21.0 +/- 9.4 versus 7.5 +/- 1.4 micrograms/gm creatinine; HP 109.0 +/- 72.9 versus 24.9 +/- 5.7 nmoles/mmole creatinine). Nineteen of the 20 SSc patients had urinary DES and HP values that were > 3 SD above the control mean. A significant elevation in the HP:LP ratio in SSc patients as compared with controls (mean +/- SD 6.9 +/- 1.5 versus 5.5 +/- 1.3) indicated a soft tissue origin for much of the increased HP.


CONCLUSIONS
Patients with SSc have higher levels of urinary cross-link amino acids specific for the degradation of mature collagen and elastin. These markers distinguish most SSc patients from healthy controls.
Stone
P J
PJ
Biochemistry Department, Boston University School of Medicine, MA 02118, USA.
Korn
J H
JH
North
H
H
Lally
E V
EV
Miller
L C
LC
Tucker
L B
LB
Strongwater
S
S
Snider
G L
GL
Franzblau
C
C
D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000652:urine; D003094:Collagen / Q000652:urine*; D003895:Desmosine / Q000652:urine; D004549:Elastin / Q000737:chemistry / Q000652:urine*; D005260:Female; D006801:Humans; D007524:Isodesmosine / Q000652:urine; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012595:Scleroderma, Systemic / Q000652:urine*
D000596:Amino Acids; D003895:Desmosine; C015484:pyridinoline; C036020:deoxypyridinoline; D003094:Collagen; D004549:Elastin; D007524:Isodesmosine