scholarly journals Immunoglobulin G4-Related Ophthalmic Disease Involving the Sclera Misdiagnosed as Intraocular Tumor: Report of One Case

2016 ◽  
Vol 2 (4) ◽  
pp. 285-288 ◽  
Author(s):  
Hiroshi Goto ◽  
Shunichiro Ueda
Keyword(s):  
Immunoglobulin G4 ◽  
Intraocular Tumor ◽  
Ophthalmic Disease

scholarly journals Upregulated Expression of Activation-Induced Cytidine Deaminase in Ocular Adnexal Marginal Zone Lymphoma with IgG4-Positive Cells

2021 ◽  
Vol 22 (8) ◽  
pp. 4083
Author(s):  
Asami Nishikori ◽  
Yoshito Nishimura ◽  
Rei Shibata ◽  
Koh-ichi Ohshima ◽  
Yuka Gion ◽  
...  
Keyword(s):  
Marginal Zone ◽  
Somatic Hypermutation ◽  
Cytidine Deaminase ◽  
Marginal Zone Lymphoma ◽  
Immunoglobulin G4 ◽  
Intensity Index ◽  
Activation Induced Cytidine Deaminase ◽  
Systemic Disorder ◽  
Lymphoplasmacytic Infiltration ◽  
Ophthalmic Disease

Immunoglobulin G4-related disease (IgG4-RD) is a systemic disorder characterized by tissue fibrosis and intense lymphoplasmacytic infiltration, causing progressive organ dysfunction. Activation-induced cytidine deaminase (AID), a deaminase normally expressed in activated B-cells in germinal centers, edits ribonucleotides to induce somatic hypermutation and class switching of immunoglobulin. While AID expression is strictly controlled under physiological conditions, chronic inflammation has been noted to induce its upregulation to propel oncogenesis. We examined AID expression in IgG4-related ophthalmic disease (IgG4-ROD; n = 16), marginal zone lymphoma with IgG4-positive cells (IgG4+ MZL; n = 11), and marginal zone lymphoma without IgG4-positive cells (IgG4- MZL; n = 12) of ocular adnexa using immunohistochemical staining. Immunohistochemistry revealed significantly higher AID-intensity index in IgG4-ROD and IgG4+ MZL than IgG4- MZL (p < 0.001 and = 0.001, respectively). The present results suggest that IgG4-RD has several specific causes of AID up-regulation in addition to inflammation, and AID may be a driver of oncogenesis in IgG4-ROD to IgG4+ MZL.

scholarly journals Distinctive Tissue and Serum MicroRNA Profile of IgG4-Related Ophthalmic Disease and MALT Lymphoma

2020 ◽  
Vol 9 (8) ◽  
pp. 2530
Author(s):  
Naoya Nezu ◽  
Yoshihiko Usui ◽  
Masaki Asakage ◽  
Hiroyuki Shimizu ◽  
Kinya Tsubota ◽  
...  
Keyword(s):  
Malt Lymphoma ◽  
Target Genes ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Therapeutic Interventions ◽  
Immunoglobulin G4 ◽  
Serum Microrna ◽  
Microrna Profile ◽  
Mitogen Activated Protein ◽  
Ophthalmic Disease

The molecular pathogenesis of orbital lymphoproliferative disorders, such as immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and orbital mucosa-associated lymphoid tissue (MALT) lymphoma, remains essentially unknown. Differentiation between the two disorders, which is important since the work-up and treatment can vary greatly, is often challenging due to the lack of specific biomarkers. Although miRNAs play an important role in the regulation of carcinogenesis and inflammation, the relationship between miRNA and orbital lymphoproliferative diseases remains unknown. We performed a comprehensive analysis of 2565 miRNAs from biopsy and serum specimens of 17 cases with IgG4-ROD, where 21 cases with orbital MALT lymphoma were performed. We identified specific miRNA signatures and their miRNA target pathways, as well as the network analysis for IgG4-ROD and orbital MALT lymphoma. Machine-learning analysis identified miR-202-3p and miR-7112-3p as the best discriminators of IgG4-ROD and orbital MALT lymphoma, respectively. Enrichment analyses of biological pathways showed that the longevity-regulating pathway in IgG4-ROD and the mitogen-activated protein kinase (MAPK) signaling pathway in orbital MALT lymphoma was most enriched by target genes of downregulated miRNAs. This is the first evidence of miRNA profiles of biopsy and serum specimens of patients with IgG4-ROD and orbital MALT lymphoma. These data will be useful for developing diagnostic and therapeutic interventions, as well as elucidating the pathogenesis of these disorders.

Immunoglobulin G4-Related Ophthalmic Disease: A Case Report

2020 ◽  
Vol 103 (7) ◽  
Keyword(s):  
Giant Cells ◽  
Orbital Apex ◽  
Orbital Apex Syndrome ◽  
Body Type ◽  
Immunoglobulin G4 ◽  
Idiopathic Orbital Inflammation ◽  
Systemic Corticosteroids ◽  
Type Giant ◽  
Ophthalmic Disease ◽  
Complete Ophthalmoplegia

The authors reported a rare case with immunoglobulin (Ig) G4-related ophthalmic disease presented with chronic progressive bilateral complete ophthalmoplegia and blindness from orbital apex syndrome. MRI brain and orbit demonstrated ill-defined infiltrative lesions at bilateral orbital apexes, bilateral optic canals, and bilateral Meckel’s caves, causing optic nerve compression and possibly optic neuropathy with generalized leptomeningeal enhancement at dura, cavernous sinus, and parotid gland. Lumbar puncture revealed few small lymphocytes, rare monocytes, very rare neutrophils with degenerative cells in background, and negative for malignancy. Serology titers for IgG subclass 4 (IgG4) had resulted in 5.959 grams per deciliter (g/dL). A dural biopsy revealed aggregate histiocytes with chronic inflammation and focal foreign body type giant cells. Motility improvement was achieved in the patient after systemic corticosteroids treatment. IgG4 serology should be considered for workup when patients present with chronic idiopathic orbital inflammation. Keywords: IgG4-related ophthalmic disease, Ophthalmoplegia, Orbital apex syndrome

scholarly journals Malignancies in Immunoglobulin G4-Related Ophthalmic Disease

2021 ◽  
Author(s):  
Kenneth K.H. LAI ◽  
Emmy Y.M. Li ◽  
Regine Y.C. Chan ◽  
Kenneth C.W. Wong ◽  
Jimmy K.S. Yu ◽  
...  
Keyword(s):  
General Population ◽  
Lacrimal Gland ◽  
Infraorbital Nerve ◽  
Immunoglobulin G4 ◽  
Orbital Mass ◽  
Serum Igg4 ◽  
Pre Treatment ◽  
Trigeminal Nerves ◽  
Ophthalmic Disease ◽  
Gland Enlargement

Abstract Purpose: Clinical phenotypes in Immunoglobulin G4-related disease (IgG4-RD) according to the affected organs affected have different risks of malignancies. We attempt to determine the association of malignances with IgG4-related ophthalmic disease (IgG4-ROD). Design: Retrospective cohort study. Methods: Review of medical records, orbital images and histopathology reports in a territory-wide cohort of patients fulfilling the “probable” or “definite” comprehensive diagnostic criteria of IgG4-RD from 2005-2019. Findings: Among 122 patients who had biopsies taken from adnexal lesions including lacrimal glands (n=108), orbital mass (n=30), infiltrated orbital fat (n=10), conjunctiva (n=2) or extraocular muscles (n=3), 16 (13%) developed malignancies over 73±48months’ follow-up. There were 9 cases of ocular adnexal lymphoma (OAL) and 7 extra-orbital malignancies. Compared with the general population, the incidence of OAL was significantly higher (standardized incidence ratios, SIRs=10.0, 95%CI=4.5-17.6) while that of extraorbital malignancy was similar. The SIR was highest within the first year (SIR=46.7, 95%CI=18.5-87.6) when 7 OAL were concomitantly diagnosed. Patients who developed OAL or extra-orbital malignancies were older than other patients when diagnosed of IgG4-ROD (64.9±7.1, 68.3±8.5 versus 55.2±15.0 years, p<0.05). Asymmetric lacrimal gland enlargement (78% versus 13%), lack of frontal (0% versus 12%) or infraorbital nerve enlargement (0% versus 36%)were associated with OAL (all p<0.05). Pre-treatment serum IgG4 level or pattern of extraorbital involvement was similar among patients with or without malignancies. Conclusion: In this biopsy-proven IgG4-ROD cohort, 7% developed OAL which was 10 times higher than the general population. Patients with asymmetric lacrimal gland enlargement or without trigeminal nerves involvement radiologically were associated with OAL.

scholarly journals Immunoglobulin G4-related ophthalmic disease

2018 ◽  
Vol 8 (1) ◽  
pp. 9 ◽  
Author(s):  
Wei-Kuang Yu ◽  
Chieh-Chih Tsai ◽  
Shu-Ching Kao ◽  
CatherineJui-Ling Liu
Keyword(s):  
Immunoglobulin G4 ◽  
Ophthalmic Disease

Low-dose ‘boom-boom’ radiotherapy for ocular lymphoma arising from IgG4-related ophthalmic disease: Case report and literature review

2021 ◽  
pp. 112067212110183
Author(s):  
Katherine Meng ◽  
Mei Chin Lim ◽  
Michelle Li Mei Poon ◽  
Gangadhara Sundar ◽  
Balamurugan Vellayappan
Keyword(s):  
Low Dose ◽  
Elevated Serum ◽  
Infraorbital Nerve ◽  
Immunoglobulin Light Chain ◽  
Immunoglobulin G4 ◽  
Systemic Involvement ◽  
Disease Case ◽  
Serum Igg4 ◽  
Ophthalmic Disease

Ocular adnexal extranodal marginal zone lymphoma (OA-EMZL) and immunoglobulin G4-related ophthalmic disease (IgG4-ROD) may exist on a continuum. Presence of immunoglobulin light-chain restriction and clonal gene rearrangement suggests presence of lymphoma; whereas bilateral, infraorbital nerve and systemic involvement accompanied by elevated serum IgG4 levels may indicate synchronous IgG4-ROD. Although steroids have been the mainstay for the treatment of IgG4-ROD, radiotherapy (RT) has been used occasionally. The reported RT doses range between 24 and 30 Gy, which can result in acute and late toxicities. A low-dose regimen of four Gy has not been previously described. We describe a patient with bilateral OA-EMZL arising from IgG4-ROD successfully treated with low dose ‘boom-boom’ radiotherapy. In addition, we review the literature for the association between these two conditions and the role of RT in their management.

scholarly journals Comprehensive Gene Analysis of IgG4-Related Ophthalmic Disease Using RNA Sequencing

2020 ◽  
Vol 9 (11) ◽  
pp. 3458
Author(s):  
Masaki Asakage ◽  
Yoshihiko Usui ◽  
Naoya Nezu ◽  
Hiroyuki Shimizu ◽  
Kinya Tsubota ◽  
...  
Keyword(s):  
Real Time ◽  
Rna Sequencing ◽  
Malt Lymphoma ◽  
Lymphoid Hyperplasia ◽  
Reactive Lymphoid Hyperplasia ◽  
Rna Seq ◽  
Immunoglobulin G4 ◽  
Tissue Samples ◽  
Biopsy Specimens ◽  
Ophthalmic Disease

High-throughput RNA sequencing (RNA-seq) uses massive parallel sequencing technology, allowing the unbiased analysis of genome-wide transcription levels and tumor mutation status. Immunoglobulin G4-related ophthalmic disease (IgG4-ROD) is a fibroinflammatory disease characterized by the enlargement of the ocular adnexal tissues. We analyzed RNA expression levels via RNA-seq in the biopsy specimens of three patients diagnosed with IgG4-ROD. Mucosa-associated lymphoid tissue (MALT) lymphoma, reactive lymphoid hyperplasia (RLH), normal lacrimal gland tissue, and adjacent adipose tissue were used as the controls (n = 3 each). RNA-seq was performed using the NextSeq 500 system, and genes with |fold change| ≥ 2 and p < 0.05 relative to the controls were defined as differentially expressed genes (DEGs) in IgG4-ROD. To validate the results of RNA-seq, real-time polymerase chain reaction (PCR) was performed in 30 IgG4-ROD and 30 orbital MALT lymphoma tissue samples. RNA-seq identified 35 up-regulated genes, including matrix metallopeptidase 12 (MMP12) and secreted phosphoprotein 1 (SPP1), in IgG4-ROD tissues when compared to all the controls. Many pathways related to the immune system were included when compared to all the controls. Expressions of MMP12 and SPP1 in IgG4-ROD tissues were confirmed by real-time PCR and immunohistochemistry. In conclusion, we identified novel DEGs, including those associated with extracellular matrix degradation, fibrosis, and inflammation, in IgG4-ROD biopsy specimens. These data provide new insights into molecular pathogenetic mechanisms and may contribute to the development of new biomarkers for diagnosis and molecular targeted drugs.

scholarly journals Immunoglobulin G4-related Ophthalmic Disease with Peripheral Eosinophilia and Elevated Immunoglobulin E Levels

2021 ◽  
Vol 20 (3) ◽  
pp. 124-128
Author(s):  
Yeon Ju Lim ◽  
Soo Jung Lee
Keyword(s):  
Immunoglobulin E ◽  
Extraocular Muscles ◽  
Diffuse Fibrosis ◽  
High Dose ◽  
Peripheral Eosinophilia ◽  
Immunoglobulin G4 ◽  
Eyelid Swelling ◽  
Laboratory Examinations ◽  
Intravenous Steroids ◽  
Ophthalmic Disease

Purpose: To report a case with peripheral eosinophilia and elevated immunoglobulin (Ig) E levels, subsequently diagnosed as IgG4-related ophthalmic disease involving the extraocular muscles.Case summary: A 56-year-old male visited the allergy department presenting with systemic urticaria and bilateral eyelid swelling that began 5 months prior. Laboratory examinations showed elevated levels of serum eosinophil and IgE, 1,309 IU/uL and 1,793 IU/mL, respectively. Orbital computed tomography revealed that all extraocular muscles and the bilateral exophthalmos were enlarged, and the patient was referred to the ophthalmology department. Eye alignment was orthophoric for all gaze directions, and limited abduction (-1) was noted in both eyes. An incisional biopsy of the extraocular muscles was conducted. Histopathological findings showed lymphoid aggregates, diffuse fibrosis, and an increased IgG4+/IgG+ plasma cell ratio of 40%, which led to the diagnosis of IgG4-related ophthalmic disease. An elevated IgG4 serum level (1,710 mg/dL) was also noted. The patient received high-dose intravenous steroids and eyelid swelling improved after two months. Levels of serum eosinophil, IgE, and IgG4 all decreased after three months.Conclusions: IgG4-related ophthalmic disease may be accompanied by eosinophilia and elevated IgE. These findings may facilitate future diagnoses of this disease.

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