Key Mechanisms of Abnormal T Cell Activation and Differentiation in IgG4-Related Ophthalmic Disease

NCT06655831 | Not Yet Recruiting DMC

• 1 other identifier: SZZ1
• Study Type: observational
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

IgG4-related disease (IgG4-RD) is a newly recognized chronic inflammatory condition caused by immune system dysfunction. It is characterized by the infiltration of IgG4+ plasma cells, dense fibrosis, and inflammation involving veins and eosinophils. Common symptoms include elevated serum IgG4 levels and the formation of tumor-like growths that can affect almost any organ, leading to pressure on tissues, irreversible damage, and even organ failure. While estimates suggest a prevalence of 0.28 to 1.08 per 100,000 people, this might be an underestimation due to limited awareness, the new definition of the disease, and its subtle onset. IgG4-related ophthalmic disease (IgG4-ROD) is a subtype of IgG4-RD that affects the eye area, particularly the lacrimal glands, extraocular muscles, and surrounding nerves. It often presents as painless swelling of the lacrimal glands in one or both eyes, sometimes with discomfort or a sensation of a foreign body. It can also cause thickening of eye muscles, leading to symptoms like bulging eyes, blurred vision, or double vision. In some cases, mass lesions in the orbit may press on the optic nerve, potentially leading to permanent vision loss. While there is currently no cure for IgG4-ROD, steroids are used as the main treatment to control inflammation and fibrosis. However, the disease often recurs, with recurrence rates for IgG4-RD reported between 24% and 63% in various studies. Understanding the causes of IgG4-ROD could help develop better treatments and reduce the chances of relapse. Studies suggest that T cells play a key role in the development of IgG4-RD, including IgG4-ROD. CD4+ T cells are the main immune cells found in affected tissues. They can help B cells multiply and produce IgG4 antibodies and contribute to tissue fibrosis by releasing certain signaling molecules. Despite treatment with rituximab, a drug that targets B cells, many IgG4-RD patients experience relapses, indicating that T cells remain important in driving the disease. Among the T cell subtypes, T follicular helper cells (Tfh) and CD4+ cytotoxic T cells (CD4+ CTLs) are particularly relevant. Tfh cells support B cells in producing IgG4 antibodies, while CD4+ CTLs can contribute to tissue fibrosis by releasing factors like TGF-β, IL-1β, and IFN-γ. However, the detailed mechanisms of how T cells become abnormally activated and differentiated in IgG4-ROD remain unclear. This study will use samples from the lacrimal glands, blood, and tears of IgG4-ROD patients to investigate how T cells become abnormally active and differentiate in this condition. The findings could identify new targets for therapy, helping to reduce the recurrence of IgG4-ROD and provide insights into treating other forms of IgG4-RD.

Conditions

IgG4-Related Diseases

Outcome Measures

Primary Outcomes (1)

• Bulk RNA-Seq Analysis of Lacrimal Gland Tissue

  Total RNA is extracted from lacrimal gland tissue using the Trizol method, followed by RNA quality assessment with an Agilent bioanalyzer. A cDNA library is constructed and sequenced using Illumina technology. Data processing includes quality control with fastp, alignment using HISAT2, and gene expression quantification with featureCounts. Differential expression analysis is performed using DESeq2, and Gene Set Enrichment Analysis (GSEA) is conducted. Immune cell composition in the tissue is analyzed using xCell and CIBERSORTx.

  At the time of enrollment.

Secondary Outcomes (2)

• Enzyme-linked Immunosorbent Assay (ELISA)

  At the time of enrollment.

• In Vitro Co-culture Experiments

  At the time of enrollment.

Study Arms (2)

IgG4-ROD

IgG4-ROD patients from the Department of Ophthalmology at Peking University Third Hospital.

Lacrimal gland ptosis

Patients with lacrimal gland ptosis undergoing surgical repositioning fromthe Department of Ophthalmology at Peking University Third Hospital.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study involves patients from the Department of Ophthalmology at Peking University Third Hospital, including lacrimal gland tissue samples from IgG4-ROD patients (experimental group) and patients with lacrimal gland ptosis undergoing surgical repositioning (control group).

You may qualify if:

• Experimental Group: IgG4-ROD patients with lacrimal gland involvement, diagnosed based on 2014 and 2020 Japanese criteria for IgG4-ROD and IgG4-RD:
• Clinical and imaging features: characteristic diffuse or localized swelling or nodular formations of the lacrimal glands.
• Serological diagnosis: Elevated serum IgG4 concentration (\>135 mg/dL).
• Histopathological diagnosis (meeting 2 of the 3 criteria below):
• Dense lymphoplasmacytic infiltration with fibrosis. IgG4+ plasma cell/IgG+ plasma cell ratio \>40%, and \>10 IgG4+ plasma cells per high-power field.
• Characteristic fibrosis, especially storiform fibrosis, or obliterative phlebitis.
• Control Group: Patients with lacrimal gland ptosis confirmed by pathology and clinical/imaging features, requiring surgical repositioning.

You may not qualify if:

• Presence of other autoimmune diseases like Sjögren's syndrome, systemic lupus erythematosus, or rheumatoid arthritis.
• Lacrimal gland pathology indicating other orbital diseases such as MALT lymphoma or inflammatory pseudotumor.

Sponsors & Collaborators

• Peking University Third Hospital: lead

Biospecimen

Retention: SAMPLES WITH DNA

Lacrimal gland tissue samples from IgG4-ROD patients and patients with lacrimal gland ptosis undergoing surgical repositioning.

MeSH Terms

Conditions

Immunoglobulin G4-Related Disease

Condition Hierarchy (Ancestors)

Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Zhengze Sun

CONTACT

+86-15898285532; 2411210462@pku.edu.cn

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2024
• First Posted: October 23, 2024
• Study Start: November 1, 2024
• Primary Completion: January 1, 2025
• Study Completion: February 1, 2025
• Last Updated: October 23, 2024

Record last verified: 2024-10