Activation of Mast-Cell-Derived Chymase in the Lacrimal Glands of Patients with IgG4-Related Ophthalmic Disease.

Yasushi Fujita,Shinji Takai,Teruyo Kida,Masashi Mimura,Yohei Sato,Denan Jin

doi:10.3390/ijms23052556

Abstract

The purpose of this present study was to investigate the distribution and expression of chymase in the lacrimal glands (LGs) of patients afflicted with IgG4-related ophthalmic disease (IgG4-ROD). LGs from patients with severe canalicular obstruction were considered the control group. Toluidine blue staining confirmed a significant increase in the number of mast cells in the LGs obtained from the IgG4-ROD patients. In addition, immunostaining of serial sections from the LGs showed a significant increase in the number of chymase-positive cells and tryptase-positive cells in the IgG4-ROD LGs compared to the normal control LGs. The mRNA expression of chymase, tryptase, TGF-β1, and collagen-I tended to increase in the IgG4-ROD LGs. Immunostaining of vimentin and α-smooth muscle actin (α-SMA) showed that myofibroblasts were the main cellular components in severely fibrotic regions of LGs in patients with IgG4-ROD. Linear regression analyses on the number of mast cells, chymase-positive cells, and tryptase-positive cells revealed significant positive correlations between those respective cells. Our findings suggest that chymase may play a role in the fibrotic disorder of IgG4-ROD LGs through the regulation of TGF-β1 activation and collagen-I deposition, and that it may be a therapeutic target for patients afflicted with IgG4-ROD.

Highlights

IgG4-related disease (IgG4-RD) is a systemic disease of unknown etiology that causes infiltration of IgG4-positive plasma cells into various organs, resulting in severe fibrosis [1]
IgG4-RD, the purpose of this present study was to compare the expression characteristics of chymase and its regulating fibrogenic mediators, as well as the quantities of chymase positive mast cells (MCs), in lacrimal glands (LGs) obtained from patients afflicted with IgG4-ROD and from patients diagnosed with severe canalicular obstruction yet normal LGs as a control
Representative hematoxylin and eosin (H&E) staining and Azan Mallory staining images of the IgG4-ROD-patient LGs and the normal control LGs are shown in Figures 1 and 2

Summary

Introduction

IgG4-related disease (IgG4-RD) is a systemic disease of unknown etiology that causes infiltration of IgG4-positive plasma cells into various organs, resulting in severe fibrosis [1]. IgG4-RD has recently become recognized as a relatively new disease concept, as, in addition to the typical target organs such as the pancreas, lacrimal glands (LGs), and salivary glands, it reportedly invades various other organs such as the hepatobiliary system, lungs, kidneys, prostate, and thyroid glands [3]. Mikulicz disease, which is well known in the field of ophthalmology, is a disorder that is reportedly accompanied by swelling of the salivary glands and the LGs in both eyes [7]. A previous study reported that Mikulicz disease causes swelling and fibrosis in other various orbital lesions, such as the extraocular muscles, the trigeminal nerve, and the optic nerve, and it has come to be collectively recognized as an IgG4-related ophthalmic disease (IgG4-ROD) [8]. In patients afflicted with IgG4-ROD, pathological examination is necessary for diagnosis, and it is characterized by fibrosis forming a mass lesion mainly composed of an infiltration of IgG4-producing plasma cells and lymphocytes [9]

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