Researcher Ariana Ringer is studying a rare autoimmune eye disease with a large team of professionals.
In recent years, diagnostic systems have advanced rapidly, allowing various pathologies to be identified with greater precision and in less time. One of these is Ocular Cicatricial Pemphigoid (OCP), a rare disease that affects the eyes.
Ariana Ringer, Clinical Physician and Rheumatologist graduated from the Faculty of Medical Sciences of the Universidad Nacional de Rosario, is developing his doctoral thesis around the study of this rare pathology, and for this reason he has worked alongside an interdisciplinary team made up of ophthalmologists, rheumatologists and allergists, evaluating more than 200 cases of patients with this autoimmune disease.
POC is a chronic, immune-mediated disease. It is linked to atopic symptoms and is sometimes considered an immuno-allergic pathology. “It is an autoimmune disease in which there is a reaction between an antigen and an antibody. It is included in the mucous membrane pemphigoid and, when it is limited to the eye, it is called POC, but this pathology itself can affect any mucosa, sometimes including the skin as well,” explained Ariana Ringer.
It begins with an exposure of antigens to the basal membrane of the conjunctiva, which is a transparent mucous membrane that lines the eyeball, and the autoimmune response is based on that. “The antigen-antibody reaction begins to be generated on that tissue, which begins to give the patient symptoms of ocular inflammation. In general, it manifests as recurrent conjunctivitis, and it takes a long time to diagnose because at first it can be confused with traditional conjunctivitis. With the passage of time, not only does the inflammation persist, but scars begin to form and that is when the after-effects begin.”
There are two types of treatments that can be implemented, depending on the particular case: a topical treatment, which is applied directly locally to the area, and a systemic treatment, via oral medication.
The specialist stressed that in the last 5 or 10 years all diagnostic methods have advanced enormously and this allows for a faster diagnosis of this type of pathology, which helps prevent the consequences in the patient. “For example, we had a diagnostic delay of 10 years and now they are being diagnosed in two to six months. This greatly reduces the risk of complications and also allows for the appropriate treatment to be carried out.”
This is a very rare disease, at least worldwide, although Ringer warned that more and more cases are being observed in our geographical area. “It may have to do with the improvement of diagnostic methods, but there may also be something environmental, environmental antigens that could have to do with the development of this disease. Like all autoimmune diseases, one is born with a genetic predisposition, and throughout life, this predisposition can be expressed as a disease or not. Many times this depends on the different stimuli that arise. For example, in the case of pemphigoid, it is believed that one of the most common stimuli would be related to the environmental issue. Patients exposed to certain environmental antigens end up generating the disease, which perhaps if they had not been exposed to these antigens they would never have generated it. However, it is not known for certain what these antigens could be.”
Although there is no strictly stipulated age at which this disease can manifest, there are certain age ranges in which it tends to appear more frequently. “The most common age range is two peaks, one between 40 and 50 years of age and then another peak of incidence at 70 or 80 years of age. However, we have identified even younger patients, and we observe that the age range affected is increasingly smaller. This could be due to the improvement in diagnostic methods, which allow the disease to be detected earlier.”
Ringer's research is directed by Dr. Ana Rosa Pérez, who is researching immunological issues, and Dr. Lorena Brance, a rheumatologist. Collaborating on this study are the rheumatologist Carlos Siegrist, the ophthalmologist German Daniel Grossi, and the physician specialized in Allergy and Immunology Gonzalo Chorzepa, as well as the doctors Marcelo Abdala, Brian Abdala and Gallo Carolina, all rheumatologists. She is accompanied in this study by fellows Florencia Elena and Valentina Grossi.
Your relationship with allergies
Ariana Ringer's research is part of her PhD thesis in Medical Sciences at UNR, in collaboration with researchers from Conicet. "What is evaluated in this work are clinical immunopathological aspects, that is, immunological and pathological anatomy of pemphigoid, because in addition to observing it clinically, we think there are alterations that could be detected at the level of blood and leukocytes. There is also the conjunctival biopsy, which would be the key method for the final diagnosis."
The research is extensive and has many facets, which are still in development. Specifically, with Dr. Gonzalo Chorzepa, who is a professor at the Faculty of Medical Sciences and a specialist in Allergy and Immunology, we studied one branch, which is the allergic component of patients with POC. “We evaluated all these characteristics in relation to the increase in immunoglobulin E in the patients’ blood. Immunoglobulin E increases when there is an allergy and what we were able to see is that half of the patients had these increased values,” explained Singer.
The professionals evaluated a series of cases of patients with this disease, most of them referred by ophthalmologists, observing the characteristics of these people. “What we did was evaluate 100 patients, how many of them had allergies, and we found a high frequency. Not only that, but we detected that in the biopsies the cells that are associated with allergies appeared, which could indicate that these cells were partly causing the disease,” said Chorzepa.
The professor and researcher at the University highlighted that when the immune system is working in optimal conditions, its objective is to stop infections, but when it begins to fail, it may be by attacking agents that a priori should be harmless, as in the case of allergies, or by attacking the body itself, as occurs in autoimmune diseases. “Ocular Cicatricial Pemphigoid is a paradigmatic example, because it is a deregulation of the immune system that, although in principle it is autoimmune, we also found that some patients have strong allergic traits in addition to this autoimmunity. These are patients who may have allergies associated by chance, but it could also function as a cofactor in the production of the disease.”
The professionals commented that not all cases also present allergies, but they did find that a percentage showed increased immunoglobulin E. “The conclusion we can give, at least with the data we have so far, is that although we treat the pemphigoid directly, there may be a percentage of patients (which may be 30 or 50 percent) who will benefit from an allergy treatment as well, because they have an allergic component added to the pemphigoid,” Ringer specified, and added: “Another thing we observed is that a quarter of the patients had some other autoimmune disease added. Among the most frequent we observed Sjögren’s syndrome and hypothyroidism among the most frequent.”
Journalist: Gonzalo J. García