Foster outlines therapeutic implications for OCP in Weisenfeld lecture

May 3

- Fort Lauderdale, FL - Calling mucus membrane pemphigoid a systematic autoimmune disease that requires systematic immunological therapy, C. Stephen Foster, MD, is hopeful he will finish the work started 18 years ago that will permanently "quiet" this blinding and progressive ocular disease.

Dr. Foster, clinical professor of ophthalmology at Harvard University and of Massachusetts Eye and Ear Infirmary, received the 2005 Mildred Weisenfeld Award for Excellence in Ophthalmology on Monday at the Association for Research in Vision and Ophthalmology annual meeting. He received the honor for his substantial basic and clinical contributions to the area of ocular inflammatory diseases.

In receiving the award, Dr. Foster delivered his Weisenfeld Lecture on "Immunopathogenesis of and Therapeutic Implications for Ocular Cicatricial Pemphigoid (OCP)."

Dr. Foster first reviewed the immunopathology of OCP and then outlined the four stages of the disease, starting as chronic conjunctivitis and showing how it progresses into an autoimmune disease. He then provided clinical evidence showing that OCP is a systematic disease and presented the factors associated with it.

Over the last 18 years, Dr. Foster pointed out that there has been a pre-occupation with eventually finding discoveries that will allow researchers to offer more than immuno-suppressing patients with OCP. To satisfy the pre-occupation, researchers need to identify the specific target antigen in the epithelial basement membrane zone that was being bound by the auto-antibody.

Dr. Foster discussed the necessary steps to identify target auto-antigens, including:

• Identifying candidatory antigens;

• Performing immunoblot studies (that);

• Isolate relevant antigen;

• Performing gene cloning to produce large amounts of antigen (that will allow the rest of the steps to follow);

• Epitope identification in the molecule, (studies on whether or not the antibodies raised are indeed pathogenic);

• Developing an enzyme-linked immunosorbent assay;

• Putting those techniques into practice.

In the long run, "also, to develop a different form of therapy for patients with this disease," he added.

Dr. Foster said the final blinding target of this disease is the cornea-the scarring, the neovascularization, the epithelial defects, and stromal ulceration. Successful therapy must affect auto-antibody production and it may be possible that "down-stream therapy" affecting fibrosis would be helpful.

"I passionately believe that the real progress comes in the future with retolerization," Dr. Foster pointed out. "I am hoping to see that before I finally decide to quit."

Until an effective therapy for OCP is found, clinicians are reduced to trying to modulate the apparent auto-immune responses through the same medications identified 25 years ago, "with a few new ones added to the mix," Dr. Foster added.

With a new therapeutic approach, Dr. Foster believes about 90% of the patients will turn out quite nicely. He is often asked: What is the goal in treating patients with pemphigoid. How much is enough? How "quiet" must OCP patients be?

"If they are not as quiet as a cuff on my shirt, then they still have ocular disease and they will progress," Dr. Foster answered. "One must stay in the hunt until one achieves that goal."