Lacrimal Gland and Orbital Lesions in LatY136F Knock-in Mice, a Model for Human IgG4-Related Ophthalmic Disease.

PURPOSE: LatY136F knock-in mice were recently proposed as an animal model for immunoglobulin G4 (IgG4)-related disease. In this study, we investigated whether LatY136F knock-in mice exhibit ophthalmic lesions, specifically in the lacrimal and Harderian glands. METHODS: Lacrimal glands, Harderian glands, and adherent lymphoid follicle lesions were dissected from LatY136F knock-in mice and wild type (WT) C57BL/6 mice between 6 and 24 weeks of age. Tissues were stained with hematoxylin-eosin, immunoglobulin G (IgG), and anti-IgG1, a homologue of human IgG4, for histopathological analysis. RESULTS: In LatY136F knock-in mice, IgG1-positive cells infiltrated the space between the lacrimal gland acinar cells at 6, 9, 12, and 20 weeks or order, and the number of IgG1-positive cells did not differ significantly between these age groups. Infiltration of IgG1-positive inflammatory cell was also observed in the Harderian glands of LatY136F knock-in mice at all ages. The ratio of IgG1/IgG-positive cells averaged 80 and 67% in the lacrimal and Harderian glands, respectively. Dense IgG1-positive lesions were also seen in tissues adjacent to the lacrimal and Harderian glands in some LatY136F knock-in mice. In contrast, there were almost no IgG1-positive cell infiltrates in the lacrimal and Harderian glands of WT mice. CONCLUSION: IgG1-positive cells infiltrate the lacrimal and Harderian glands of LatY136F knock-in mice, indicating that LatY136F knock-in mice could be a representative animal model for IgG4-related ophthalmic disease.

Cases with IgG4-related ophthalmic disease with mass lesions surrounding the optic nerve.

PURPOSE: IgG4-related ophthalmic disease (IgG4-ROD) is a lymphoproliferative disorder with representative symptoms including lacrimal gland enlargement (Mikulicz disease), masses around the trigeminal nerves, and extraocular muscle swelling. Herein, we describe cases of IgG4-ROD with lesions surrounding the optic nerve. METHODS: Of the 56 consecutive patients (35 men and 21 women) with a "definite case" of IgG4-ROD diagnosed from November 2004 through December 2019 at Kanazawa University hospital, seven patients presented with mass lesions around the optic nerve based on magnetic resonance imaging, and four patients showed symptoms of optic neuropathy. The clinical courses of these seven cases were reviewed. RESULTS: Among the 56 cases of IgG4-ROD, seven cases had lesions surrounding the optic nerve and all of these patients were male. The male dominance in the patient group with lesions surrounding the optic nerve was statistically significant based on a Chi-squared test (p < 0.001). Lacrimal gland swelling was also present in all seven cases, extraocular muscle enlargement in six cases, and trigeminal (infraorbital and supraorbital) nerve enlargement in six cases. Four patients showed deteriorated visual acuity compatible with optic neuropathy. These seven patients were treated by systemic steroid administration. Overall, in cases with optic neuropathy, visual function responded well to steroid therapy; however, recovery was limited in the worst case. CONCLUSIONS AND IMPORTANCE: Attention should be paid for mass lesions surrounding the optic nerve in patients with IgG4-related disease, especially in cases with high serum IgG4 levels.

Imaging and pathological features of gastric lesion of immunoglobulin G4-related disease: A case report and review of the recent literature.

We describe a 67-year-old man with immunoglobulin G4-related disease (IgG4-RD) presenting with optic neuropathy, dacryoadenitis, periaortitis, retroperitoneal fibrosis, and a gastric mass-like lesion. A mass-like lesion measuring 52 × 40 mm in the antrum of the stomach was found incidentally through whole-body screening for other organ involvement of IgG4-RD using contrast-enhanced computed tomography (CT). Histology of the stomach revealed that the lesion was also IgG4-related and was located in the submucosal layer extending to the subserosal region. This case suggests that the stomach can also be a site of involvement of IgG4-RD.

Clinical Aspects of IgG4-Related Orbital Inflammation in a Case Series of Ocular Adnexal Lymphoproliferative Disorders.

The most frequent ocular adnexal tumors and simulating lesions are lymphoproliferative disorders (LPDs), including malignant lymphomas and orbital inflammation with lymphoid hyperplasia or infiltration. IgG4-related orbital inflammation (IgG4-ROI) often involves lacrimal glands and other orbital tissues and is an important differential diagnosis. The present study evaluated clinical aspects of IgG4-ROI in a case series of orbital LPD. Sixty-two consecutive cases of orbital LPD, pathologically diagnosed from November, 2004, through March, 2011, were investigated. Histological types were 22 cases with MALT lymphoma, 11 cases with diffuse large B-cell lymphoma (DLBCL), 3 cases with other malignant lymphomas, 16 cases with IgG4-ROI, and 10 cases with non-IgG4-ROI. Ages of the IgG4-ROI group (56 ± 10 yrs) were significantly lower than the MALT lymphoma (71 ± 12 yrs) and DLBCL (75 ± 14 yrs) groups. Orbital lesions other than lacrimal glands were present in six cases including extraocular muscle swelling, mass lesions surrounding the optic nerve, and supraorbital and infraorbital nerves enlargements. Although none of the malignant lymphomas were related to IgG4, previous evidence suggested that malignant lymphomas can arise from IgG4-ROI. Based on this study (26%) and another report (33%), it is likely that nearly a quarter of orbital LPD are IgG4-ROI.