Leucine-rich a-2 glycoprotein as a potential biomarker of idiopathic multicentric Castleman disease with pulmonary involvement: a single-center case-control study from Japan.

Abstract

BackgroundThere are no known biomarkers for monitoring disease activity in idiopathic multicentric Castleman disease (MCD) with pulmonary involvement. We investigated the utility of serum leucine-rich α2-glycoprotein levels, which reflects interleukin 6 independent inflammatory change, for monitoring disease activity in patients with idiopathic MCD with pulmonary involvement.MethodsWe retrospectively examined cases of idiopathic MCD diagnosed at Osaka University Hospital. The serum levels of leucine-rich α2-glycoprotein were compared between patients with idiopathic MCD and healthy controls. The difference in leucine-rich α2-glycoprotein levels before and after treatment (∆leucine-rich α2-glycoprotein) was evaluated with respect to the relationship with pulmonary function. In addition, the relationship between cytokine and chemokine profiles and the leucine-rich α2-glycoprotein concentration was investigated. The results were analyzed using pathway analysis.ResultsThe leucine-rich α2-glycoprotein concentrations were significantly higher in treatment-naïve patients (n=5) than in healthy controls (n=3) (P=0.035). Further, the ∆leucine-rich α2-glycoprotein concentration was significantly correlated with ∆ percent diffusing capacity of the lung for carbon monoxide (r=−0.88, P=0.049) and tended to correlate with ∆ percent vital capacity (r=−0.68, P=0.21) although the difference was not significant for the latter association. The concentrations of chemokines and cytokines, such as CXCL9, CXCL11, CXCL1, and a proliferation-inducing ligand, were higher in the patient group than in the healthy control group. Enrichment analysis indicated that leucine-rich α2-glycoprotein could be elevated via the upregulation of chemokines in patients with idiopathic MCD using these parameters.ConclusionsLeucine-rich a2-glycoprotein may be useful for monitoring disease activity in patients with idiopathic MCD with pulmonary involvement.