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 [LPJ) in systemic sderosis (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 f SD levels of urinary DES and IDES were elevated in SSc patients by 2-3-fold, and urinary HP and LP by --fold, compared with controls (DES 21.0 f 9.4 versus 7.5 f 1.4 pglgm creatinine; HP 109.0 f 72.9 versus 24.9 k 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 f SD 6.9 2 1.5 versus Conclusion. 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.Systemic sclerosis (SSc; scleroderma) is a disease in which excessive connective tissue is found in the dermis, blood vessels, and internal organs (1). Excessive collagen deposition results from an imbalance between the amount of newly synthesized collagen incorporated into the extracellular matrix by the formation of collagen cross-links and the amount of both newly synthesized and mature collagens degraded. Studies of this imbalance in SSc have focused on excess collagen synthesis deriving from overproduction by fibroblasts. While elastin accumulation has been reported in other fibrotic conditions (2,3), abnormalities of elastin metabolism in SSc have not been reported. Similarly, little work has been done on the in vivo degradation of collagen or elastin in SSc, which might regulate the net amount of deposited protein.Degradation of mature (cross-linked) elastin can be quantified by measuring the amount of urinary desmosine (DES) and isodesmosine (IDES), cross-link amino acids derived exclusively from mature elastin (4). Degradation of mature fibrillar (types I, 11, 111, V, and XI) collagen can be quantified by measurement of hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) (5). The cross-link amino acids DES, IDES, HP, and LP are not appreciably metabolized, but are excreted intact in the urine, reflecting mature elastin and collagen solubilization in vivo (6,7).We measured urinary DES, IDES, HP, and LP in SSc patients and control subjects, with an assay that
