Serum checkpoint molecules in patients with IgG4-related disease (IgG4-RD).

Abstract

BACKGROUND:

Immunoglobulin G4-related disease (IgG4-RD) is characterized by increased serum IgG4 concentration and infiltration of IgG4+ plasma cells in the affected organs. The present study aimed to characterize the serum levels of coinhibitory checkpoint molecule, T cell immunoglobulin and mucin-containing-molecule-3 (TIM-3), and its ligand, galectin-9 (Gal-9), among IgG4-related disease in patients with IgG4-RD patients with various organ involvements.

METHODS:

Serum samples were collected from untreated 59 patients with IgG4-RD, 13 patients with rheumatoid arthritis, and 37 healthy controls (HCs). HCs lacked chronic medical diseases or conditions and did not take prescription medications or over-the-counter medications within 7 days. Patients with IgG4-RD (n = 57) were subdivided into those with visceral involvement (n = 38) and those without visceral involvement (n = 21). Serum levels of Gal-9 and soluble TIM-3 (sTIM-3) were determined using enzyme-linked immunosorbent assay (ELISA). The results were compared with the clinical phenotypes of IgG4-RD.

RESULTS:

In untreated patients with IgG4-RD, serum levels of Gal-9 and sTIM-3 were significantly higher than in RA patients as well as in healthy controls. There were significant correlations between the serum levels of Gal-9 or sTIM-3 and serum levels of IgG, BAFF, or sIL-2R. However, there was no significant correlation between the serum levels of Gal-9 or sTIM-3 and serum IgG4 concentrations. Serum levels of sTIM-3 were significantly higher in a subset of patients with visceral involvements than in those without visceral involvements. However, there was no significant difference in the serum levels of Gal-9 between IgG4-RD patients with and without visceral involvements, although both Gal-9 and sTIM-3 were elevated in untreated IgG4-RD patients, and the levels of these checkpoint molecules remained unchanged after steroid therapy.

CONCLUSION:

Serum levels of Gal-9 and sTIM-3 were significantly elevated in untreated patients with IgG4-RD. Furthermore, serum levels of sTIM-3 were significantly higher in IgG4-RD patients with visceral involvements. These checkpoint molecules could be a potentially useful biomarker for IgG4-RD and for assessing the clinical phenotypes of IgG4-RD.

• Authors: Haruki Matsumoto, Yuya Fujita, Naoki Matsuoka, Jumpei Temmoku, Makiko Yashiro-Furuya, Tomoyuki Asano, Shuzo Sato, Hiroshi Watanabe, Eiji Suzuki, Sosuke Tsuji, Shoichi Fukui, Masataka Umeda, Naoki Iwamoto, Atsushi Kawakami, Kiyoshi Migita
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 23 Issue 1 Pg. 148 (05 24 2021) ISSN: 1478-6362 [Electronic] England
• PMID: 34030721 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Immunoglobulin G

Topics

• Arthritis, Rheumatoid
• Biomarkers
• Humans
• Immunoglobulin G
• Immunoglobulin G4-Related Disease
• Plasma Cells