Desmosine as a Novel Biomarker Candidate for Pulmonary and Cutaneous Chronic Graft-Versus-Host Disease

Pulmonary and cutaneous fibrotic manifestations are common in chronic graft-versus-host disease (cGVHD) and can significantly reduce patients' quality of life and functional status. Plasma desmosine (pDES), a byproduct of elastin breakdown, may serve as a biomarker for fibrotic tissue involvement in cGVHD. The primmary objective was to evaluate the association between plasma desmosine levels and pulmonary and cutaneous manifestations in patients with cGVHD. We measured pDES levels in 81 cGVHD patients enrolled in the NIH cGVHD Natural History Study using liquid chromatography-tandem mass spectrometry. Patients were evaluated for bronchiolitis obliterans syndrome (BOS) according to NIH consensus criteria, lung involvement using FEV1-based NIH lung cGVHD scores, and skin sclerosis as defined by NIH skin feature scores. Statistical analyses included logistic and linear regression, adjusted for relevant covariates. The median pDES level was 0.39 ng/mL, with 77% of patients exceeding the upper limit of normal (0.280 ng/mL). No significant association was observed between pDES levels and BOS diagnosis (odds ratio [OR]: 1.15, 95% confidence interval [CI]: 0.89-1.52, P = .31). Among patients with skin sclerosis, 84% had elevated pDES levels compared with 67% of those without sclerosis. Similarly, 82% of patients with impaired lung function had elevated pDES levels versus 56% of those with normal lung function. On multivariate analysis, each 0.1 ng/mL increase in pDES was associated with a twofold increase in the odds of impaired lung function (OR: 1.96, 95% CI: 1.13-3.91; P = .032) and higher odds of skin sclerosis (OR: 1.36, 95% CI 1.02-1.92; P = .048). Elevated pDES levels were significantly associated with pulmonary function impairment and skin sclerosis in cGVHD, supporting the potential role of desmosine as a biomarker of organ involvement. Although these findings should be interpreted cautiously, they provide a strong rationale for evaluation in larger, prospective cohorts. Future studies are warranted to validate these observations and to clarify the potential utility of pDES as a prognostic biomarker, as well as its role in monitoring disease progression and treatment response.