Comprehensive analysis of protein-expression changes specific to immunoglobulin G4-related disease

• Published in: Clinica chimica acta 2021-12, Vol.523, p.45-57
• Main Authors: Kawanami, Takafumi, Kawanami-Iwao, Haruka, Takata, Takanobu, Ishigaki, Yasuhito, Tomosugi, Naohisa, Takegami, Tsutomu, Yanagisawa, Hiroto, Fujimoto, Shino, Sakai, Tomoyuki, Fujita, Yoshimasa, Yamada, Kazunori, Mizuta, Shuichi, Kawabata, Hiroshi, Fukushima, Toshihiro, Hirose, Yuko, Masaki, Yasufumi
• Format: Article
• Language: English
• Subjects: Enzyme-Linked Immunosorbent Assay; Humans; IgG4 related disease; Immunoglobulin G; Immunoglobulin G4-Related Disease; Leucine-rich alpha-2-glycoprotein (LRG-1); Protein Processing, Post-Translational; Proteomics; Serum proteomics; Two-dimensional difference gel electrophoresis (2D-DIGE)
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2021.08.025

•Serum A1AT, LRG-1, and clusterin were significantly elevated in IgG4-related disease.•LRG-1 levels were halved after 1 month of prednisolone treatment.•LRG-1 could serve as a novel biomarker of IgG4-related diseases. Immunoglobulin 4 (IgG4)-related disease (IgG4-RD) is a lymphoproliferative disorder characterized by elevated serum IgG4 levels and tissue infiltration of IgG4-positive plasma cells. We analyzed the serum proteins, whose levels varied based on the disease state and treatment. Serum proteins from patients with IgG4-related disease and healthy subjects were resolved using two-dimensional electrophoresis, silver-stained, and scanned. Alternatively, the proteins were labeled with Cy2, Cy3, and Cy5 before electrophoresis. The proteins, whose expression differed significantly between patients and healthy individuals, and between before and after steroid treatment, were identified and validated using enzyme-linked immunosorbent assays. Pre-treatment sera from patients with IgG4-related disease was characterized by increased levels of immunoglobulins such as IgG1, IgG4; inflammatory factors such as α-1 antitrypsin (A1AT); and proteins associated with immune system regulation such as clusterin and leucine-rich α-2-glycoprotein (LRG-1). The serum levels of A1AT, LRG-1 and clusterin, during treatment with prednisolone for up to 12 months revealed that LRG-1 levels were halved after 1 month of treatment, comparable to those in healthy subjects; LRG-1 levels remained normal until the end of treatment. LRG-1 could serve as a novel biomarker of IgG4-related diseases.