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Study suggests future way to treat chronic eye problems and lymphoma in Sjogren's Syndrome.

 chronic eye problems and lymphoma in Sjogren's Syndrome.

This study published in October 2018 suggests certain cells may be the way to treat the chronic dry eye that is characteristic of Sjogren's Syndrome. (SS)

BACKGROUND INFORMATION

Impaired cells in the lacrimal glands of the eye appear to drive the production of autoantibodies and cause the chronic dry eye that patients with SS experience according to this research.

These impaired cells are named marginal zone B (MZB) cells. They have been previously reported in the salivary glands in SS patients and are involved in production of autoantibodies and gland destruction.

In humans, MZB cells are also found in lymphoid tissue at sites that include the salivary gland, lacrimal duct, and conjunctiva and in secondary lymphoid organs such as the spleen.

Finding autoreactive MZB cells in salivary glands of SS patients is closely related to lymphoma development.

Emerging evidence supports an important role of MZB cells in SS development and suggests MZB cells as a potential target for therapy in SS.

METHODS

In this study, they used a thrombospondin-1 deficient (TSP1−/−) mouse model of SS that develops eye symptoms similar to those seen in humans with SS.

Scientists examined the mice to understand the function of MZB cells in the development of SS and the eye. These mice had an increased amount of MZB cells in the spleen and lacrimal glands compared to normal mice.

RESULTS

Our results provide the evidence that the MZB compartment is enlarged and dysregulated in TSP1−/− mice, the increased MZBs contribute to antibody response against eye-derived antigens, and they are regulated by the TSP-derived peptide known to ameliorate SS-related ocular symptoms, reported the researchers.



Figure. Detection of MZB cells in the conjunctiva (ocular mucosal tissue).
Representative images of immunostained sections of conjunctiva from WT and TSP1−/− mice
(200×; scale bar, 20 µm) are shown. Frozen tissue sections were stained for B220 (red) and CD1d (green). Nuclei were stained with DAPI (blue). Cells positive for both B220 and CD1d represent MZB cells and are marked with white arrows.


MZB cells in the mice also had high levels of the immune-related molecules interleukin-6 and -10, which is associated with disease processes in the eye.

Results also showed that topical application of a thrombospondin-1-derived peptide (N1K), known to ease ocular symptoms in Sjogren’s syndrome, significantly reduced the antibody response against an eye-derived protein, and reduced the size of the MZB compartment of the spleen.

Collectively, these results support a strong potential of MZB cells in generating an immune response against eye-derived antigens and suggest their potential contribution to SS - associated ocular manifestations, the researchers wrote.

Thus, MZB cells likely represent a common therapeutic target that addresses SS pathology in both [spleen and lacrimal] exocrine glands, they added.

MZB cells are key in the greater risk for lymphoma in Sjogren’s patients, so the findings also suggest a new treatment target for lymphoma patients.

The results demonstrate dysregulation of MZB cells and highlight their role in SS chronic ocular surface disease.

These results indicate that more MZB cells found in eye tissues suggest that MZB cells are associated with the development of the disease.

Dysregulated Marginal Zone B Cell Compartment in a Mouse Model of Sjögren’s Syndrome with Ocular Inflammation was published in the International Journal of Molecular Sciences.

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