Complement and Meibomian Gland Dysfunction in Sjögren’s Disease
Abstract (summary)
Meibomian gland dysfunction (MGD) is a common complication of Sjögren’s disease (SjD) and a major contributor to dry eye disease associated with SjD (SjD-DE). While previous investigations have characterized the clinical features of MGD among SjD patients, the molecular mechanisms driving this condition have been rarely explored. As a systemic autoimmune disease, SjD is often characterized by chronic inflammation and tissue damage, where the complement system (CS) is considered a potential contributor to its broader pathophysiology. Although the CS is highlighted in literature to promote chronic inflammation in related autoimmune diseases such as systemic lupus erythematosus (SLE), its role at the ocular surface and within the meibomian glands (MGs) has not been explored. Consequently, this dissertation seeks to investigate whether local complement activity is linked to MGD associated with SjD (SjD-MGD).
To achieve the dissertation goals, this research was divided into in vitro and clinical components. First, the ability of MGs to locally produce complement proteins was assessed in vitro using immortalized human meibomian gland epithelial cells (HMGECs). These cells were evaluated for the presence and secretion of functionally competent complement proteins. Second, a clinical study was conducted to assess the association of tear complement activation and clinical MGD signs. Finally, the localized complement environment within the meibum of SjD-MGD patients was evaluated and compared with patients presenting with primary MGD and healthy controls to characterize intra-glandular complement involvement.
Our results demonstrate that MGs may possess the ability to locally produce complement proteins, which could be secreted into the meibum. In our clinical studies, complement activation products in tears were found to be correlated with MGD signs such as upper MG dropout and poor meibum expressibility. A deeper dive into the microenvironment of the MG through proteomic analysis of expressed meibum revealed that patients with SjD-MGD exhibited significantly higher levels of complement proteins C3 and C4 compared to controls. Altogether, these findings suggest that the local complement system within the MGs may play a role in SjD-MGD. This research provides a preliminary understanding of the pathophysiology of SjD-MGD and identifies the complement system as a potential mechanism for future targeted therapeutic interventions.
Indexing (details)
Optometry;
Immunology
0210: Optometry
0982: Immunology
| Funding Agency | Grant Number |
|---|---|
| National Eye Institute | K23 EY028629-01 |