NEW YORK (Reuters Health) - Eyedrops containing an anti-CD4 monoclonal antibody prevent autoimmune destruction of lacrimal glands in a mouse model of Sjogren’s syndrome, Japanese researchers report.
The findings represent a new strategy for treating eye symptoms in patients with Sjogren’s syndrome and other conditions, and could be applicable to antibody-based topical treatments for other diseases, Dr. Yuki Hayashi of the University of Tokushima and colleagues write in the September issue of Arthritis & Rheumatism.
The researchers used NFS/sld-mutant mice thymectomized at 3 days of age, which begin to develop Sjogren’s syndrome-like pathology at 4 weeks. Animals were given the drops in both eyes once daily from 4 to 8 weeks of age or from 10 to 12 weeks of age.
When given earlier on, the drops prevented the development of autoimmune pathology in the animals’ lacrimal glands, but not their salivary glands. Tear volume in the treated mice returned to levels similar to those seen in control mice given immunoglobulin G. When given at 10 to 12 weeks, the eyedrops slowed progression of the disease in lacrimal glands but did not affect tear volume.
Further studies found that the eyedrops did not delete CD4 T cells, but instead prevented their local activation. The eyedrops also blocked the expansion of CD4 T cells targeting alpha-fodrin, an autoantigen that is thought to be central to the onset and progression of Sjogren’s syndrome, and reduced serum titer of alpha-fodrin autoantibodies.
Dr. Hayashi and colleagues note that cyclosporin A eyedrops have been tested in Sjogren’s syndrome patients, but that this agent carries the risk of side effects even with local administration.
“Antibodies have the ability to bind very specifically to their largest receptor, which suggests that it is possible to establish a therapeutic strategy with fewer side effects,” they write.
“We did not observe any changes in cell number or activation status in the spleen with eyedrop administration of CD4, which repudiates the possibility that anti-CD4 mAb enters the circulation.”
Source: Arthritis Rheum 2004;50:2903-2910. [ Google search on this article ]
MeSH Headings:Animal Diseases: Disease Models, Animal: Sjogren’s Syndrome: Drugs, Investigational: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
