Serum KL-6 a better predictor of progressive SSc-ILD than CYFRA 21-1

A recent study has found that serum KL-6, a mucin-like glycoprotein (MUC1) expressed by type II pneumocytes, is associated with decline in lung function in systemic sclerosis (SSc), indicating its clinical utility in risk stratification for progressive SSc-related interstitial lung disease (ILD).

The investigators measured serum KL-6 and CYFRA 21-1, expressed by alveolar and bronchiolar epithelial cells, in a retrospective (n=189) and a prospective (n=118) cohort of SSc patients. Genotyping of MUC1 rs4072037 was also carried out. The relationship with change in lung function parameters over time was assessed in linear mixed-effect models, while the association with survival was examined through Cox proportional hazard analysis.

In both cohorts, KL-6 and CYFRA 21-1 were highest in patients with lung involvement, as well as in those with extensive vs limited ILD; additionally, KL-6 was greater in patients carrying the MUC1 rs4072037 G allele. KL-6, but not CYFRA 21-1, significantly correlated with diffusing capacity of the lung for carbon monoxide (DL_CO) decline in patients with SSc-ILD in both cohorts (p=0.001 and p=0.004, respectively) and with forced vital capacity (FVC) decline in the retrospective (p=0.005) but not in the prospective cohort.

Multivariable analysis, adjusting for age, gender, ethnicity, smoking history, and MUC1 allele carriage, revealed that KL-6 remained predictive of DL_CO in both milder (p=0.007) and more severe disease (p=0.02) when combining the cohorts and subgrouping by severity (median composite physiological index, 45.97).

“Ultimately, we need to develop an individualized risk index that incorporates clinical variables including ILD severity, integrated by easily obtainable biomarkers to inform selective early treatment and frequent monitoring of patients with SSc‐ILD at high risk of progression,” the investigators said.