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

So Takata; Yoshito Takeda; Haruhiko Hirata; Yuya Shirai; Takayoshi Morita; Yu Futami; Yujiro Naito; Kentaro Masuhiro; Takayuki Shiroyama; Kotaro Miyake; Tetsuji Naka; Atsushi Kumanogoh

doi:10.21037/jtd-21-1973

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

J Thorac Dis. 2022 May;14(5):1332-1341. doi: 10.21037/jtd-21-1973.

Authors

Affiliations

¹ Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan.
² Center of Intractable Immune Disease, Kochi Medical School, Kochi University, Kochi, Japan.
³ Department of Immunopathology, World Premier International Research Center Initiative, Immunology Frontier Research Center, Osaka University, Osaka, Japan.
⁴ Integrated Frontier Research for the Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan.
⁵ Center for Infectious Diseases for Education and Research, Osaka University, Osaka, Japan.

Abstract

Background: There 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.

Methods: We 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.

Results: The 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.

Conclusions: Leucine-rich a2-glycoprotein may be useful for monitoring disease activity in patients with idiopathic MCD with pulmonary involvement.

Keywords: Multicentric Castleman disease (MCD); chemokine; disease activity; leucine-rich α2-glycoprotein.