News Report / Profile
Patrícia Costa Reis - The doctor who pursues autoimmunity
Patrícia Costa Reis is a paediatrician, researcher and a teacher at our Faculty. It was between consultations that we managed to get a hold of her for a brief interview on the research project that launched her into the limelight. After all, being awarded the L’Oréal Prize for Women in Science, as she says: “It is an acknowledgment for what I have already done and a great incentive to continue to do clinical work and research at the same time.”.
In a very transparent way, during our conversation, she reveals a focused character and a passion for research on autoimmune diseases. Although she has never said it, it seems that it is among the children that she feels fulfilled, especially those who need her support the most. We talked a little bit about everything: research projects, clinical cases, her time in the United States, the role of women in science, and her role as a teacher of fourth- and sixth-year medical students, and guess what? We almost forgot about the L’Oréal Prize.
Before addressing the L’Oréal Prize for Women in Science, I asked her to tell us a bit about the métier of her research. How did you first became interested in associating the study of autoimmune diseases, such as lupus, to the intestine?
Patrícia Costa Reis: In one of the projects I developed during my PhD, I found that patients with lupus, in comparison to healthy individuals, had a higher concentration of LPS in the blood, a component of the outer membrane of negative Gram bacteria.
How does that finding relate to the intestine?
Patrícia Costa Reis: Given the increase in circulating LPS in lupus patients and the fact that our intestine contains a complex microbiome, I hypothesized that patients with lupus have greater intestinal permeability, which may allow the passage of bacteria, bacterial components, or bacterial products into the bloodstream. This phenomenon may be relevant to perpetuate the chronic activation of the immune system that occurs in lupus. Last year, an article published in Science showed that, in a mono-colonized murine model of autoimmunity, there was greater intestinal permeability and when vaccines or antibiotics were used to interfere with the microbiome, autoimmunity manifestations ceased. This paper proved the association between microbiota, intestinal permeability and autoimmunity.
Also transposable to humans... Would you say that there is a higher prevalence in women than in men?
Patrícia Costa Reis: Lupus is much more prevalent in women. Of course, hormones play an important role in the pathogenesis of lupus, but even in the pre-pubertal stage, there are more girls than boys with lupus.
Why is that?
Patrícia Costa Reis: It is known that there are genes located on the X chromosome that are relevant for Lupus susceptibility. For example, women with Turner Syndrome, who only have one X chromosome, have a lower prevalence of lupus. While men with Klinefelter Syndrome, with 2 X chromosomes and 1 Y chromosome have a higher prevalence of Lupus. Everything leads one to believe that genes on the X, chromosome are relevant to the onset of Lupus, so there is a clear gender difference.
You said recently that the disease also manifested at a paediatric age. Is the disease also common in children?
Patrícia Costa Reis: The prevalence of Lupus in paediatric age is lower than the prevalence in adults. Only 15%of patients with lupus are diagnosed before the age of 18.
Is it a genetic disorder?
Patrícia Costa Reis: Yes. Lupus is a multifactorial disease and there are clearly a number of genetic factors that favour its appearance. And, in addition to the genetic component, we also have to consider environmental stimuli, such as sun exposure. Lupus tends to be diagnosed in the summer due to increased sun exposure, and there are also more recurrences at this time of year. Sun exposure leads to increased apoptosis (cell death), which favours autoimmunity and inflammation.
Has there been a case of paediatric Lupus that has touched you in a special way?
Patrícia Costa Reis: Many, indeed. When we are following these children, we know they feel different from their peers. The disease's activity, the fight against fatigue and chronic pain, the adverse effects of the drugs, multiple visits to the hospital and, sometimes, the need for hospitalization, cause disruption to a normal childhood and adolescence. School failure and unemployment in patients with lupus is much higher than in the general population. All of this is a stimulus to develop new therapeutic strategies, with fewer adverse effects, to try to substantially improve these patients' quality of life. I spent 6 months at the Paediatric Rheumatology Unit at Columbia University, in New York, and followed a cohort of 150 children, mostly Hispanic and African American, with Lupus. The disease manifests itself very aggressively, often affecting the kidneys and the central nervous system, so during these 6 months I met a lot of children that marked me and that led me to want to do research in this area.
Regarding the L’Oréal, prize, how do you see this recognition?
Patrícia Costa Reis: It is an acknowledgment for what I have already done and a great incentive to continue to do clinical work and research at the same time. With the award, I was able to get funding to launch the new project on intestinal permeability and the microbiome in lupus that I would like to develop.
What were your biggest contributions to science so far?
Patrícia Costa Reis: During my Doctorates, I dedicated myself to the study of biomarkers in lupic nephritis, more precisely I studied the role of microRNAs in this disease. They are regulatory molecules that control multiple genes. MicroRNAs can be measured in biological fluids (blood and urine) and are therefore increasingly used as biomarkers in different diseases. I identified two microRNAs in the kidneys and urine that correlate with the activity of lupus nephritis and found that these microRNAs were associated with increased expression of HER2 protein. I demonstrated that this protein was very high in the kidneys and urine of patients with lupus nephritis and correlated with the disease's activity. I am now developing a multicentre study in the US, for children with lupus to determine the role of the HER2 protein in predicting relapses and responses to treatment. There are already drugs against HER2, which are used for breast cancer treatment, so I am also collaborating with a group of researchers to study the effect of these drugs in an animal model. This can be a completely new way of treating lupic nephritis.
Professor, how would you describe the role of women in science today? For example, here at the Faculty we know that there are already more female students than male students in medical classes. In your opinion, are we witnessing a paradigm shift?
Patrícia Costa Reis: Science and academia reflect society. Globally, only one-third of researchers are women, so generally speaking, we are still very far away from achieving gender equality. Nevertheless, when we look at science in Portugal, we are rather better than other countries. Approximately50%of Portuguese researchers working in Portugal or abroad are women and annually more women than men become Doctors. In terms of top-level positions in science, there is still no equality, but we do have, for example, women at the forefront of major scientific institutions, such as the Gulbenkian Science Institute and the Institute of Molecular Medicine. In addition, we have an incredible group of female scientists in our country: Prof. Leonor Parreira, Prof. Maria do Carmo Fonseca, Prof. Maria Mota, Prof. Mónica Bettencourt Dias, Prof. Cláudia Faria, among others, who are remarkable examples of enormous energy, vision, curiosity, commitment and intelligence and which will certainly be inspiring for a new generation of women researchers.
Have you ever felt that a door was closed because you are a woman?
Patrícia Costa Reis: No. Never. I got into the Faculty of Medicine and my specialty, always in an objective way, through a national selection of grades in objective exams. Even for the projects to which I applied through the FCT and other institutions, the selection process always depended on the project, so I never felt wronged.
In terms of teaching, what are your responsibilities at the Faculty of Medicine today?
Patrícia Costa Reis: I am a paediatrics teacher. I teach practical classes to 4th-year students approximately 2 to 4hours a week, as well as paediatrics theoretical-practical classes to 5th-year students. And I also teach 6th-grade and masters' course students.
Which students are the most demanding?
Patrícia Costa Reis: There's something special about 6th-year students, because I have the opportunity of having one student with me for a month and a half, so there is room for more discussion about the patients that we are going to see and, therefore, creating closer proximity. I also like teaching 4th-year students because I try to spark their interest in paediatrics and the importance of knowing how to collect clinical history correctly. The large number of students per teacher is a challenge. Students are demanding and I'm glad they are, because they drive me to always do better.
Isabel C. Varela