Blood MMP-7 and TNF-α levels linked to FEV1 decline in adult PLCH

TNF-α and MMP-7 levels are potential prognostic blood biomarkers in pulmonary Langerhans cell histiocytosis. In patients with declining forced expiratory volume in one second (FEV1) profiles over time, the levels of TNF-α and MMP-7 at diagnosis were significantly greater than in patients whose FEV1 profiles remained stable over a median follow-up of 3.6 years [IQR 2.2–5.1].

The natural history of pulmonary Langerhans cell histiocytosis (PLCH) is unpredictable. The aim of the study was to evaluate the levels of various blood mediators in PLCH patients at diagnosis and explore their relationships with FEV1 outcomes.

Multiplex immunoassays were used to measure at diagnosis the serum concentrations of thirty mediators in patients with stable vs. declining FEV1. Multivariable-adjusted logistic regression models, accounting for matched variables of age, sex, and daily tobacco consumption, were used to compare concentrations between patients stratified on the basis of their FEV1 values.

Nine patients with declining FEV1 profiles over time who had an available blood sample at the time of PLCH diagnosis were paired with 16 patients whose FEV1 profiles remained stable. The levels of two biomarkers, TNF-α and MMP-7, were significantly greater in patients with a decreased FEV1 than in those with a stable FEV1 in the univariable analysis after adjustment for matching variables.

The median serum levels of TNF-α were 137 [75–358] pg/mL in the declining FEV1 group and 60 [45–92] pg/mL in the stable FEV1 group (p = 0.032). The median MMP-7 levels were 16344 [13318–18000] pg/mL and 11555 [9796–12495] pg/mL, respectively (p = 0.047).

There was a negative correlation between FEV1 values and MMP-7 levels (rho = −0.65, p = 0.001) but not with TNF-α levels (rho = −0.33, p = 0.14).