The yin and yang of rheumatoid arthritis.

نویسنده

  • Karen Birmingham
چکیده

major prizes awarded each year for biomedical research are often given to two or three scientists who have contributed to the development of a field, usually at different stages and from different laboratories. But sometimes an award acknowledges teamwork — a partnership that changes the course of medical science. This year’s Albert Lasker Award for Clinical Medical Research is a classic example. Friends and colleagues for 20 years, Sir Ravinder Maini and Marc Feldmann won the 2003 prize for translational research, which started with identification of a molecular cause of rheumatoid arthritis (RA) in animal models, moved through its validation in human tissue, and culminated in the development of a new class of drugs for the disease. Feldmann began his career as a doctor in Australia, where he found that “the realities of medical practice served only to reveal how much we didn’t understand about mechanisms of disease.” He switched to basic research, earned a PhD, and in 1972 went to London to work as a postdoc at a new department of immunology at University College. Sir Ravinder was also a physician with a keen interest in research. As a fellow in the relatively new subject of clinical immunology, he published his first paper in Nature in 1968, on a lymphocyte extract in RA patients. Their collaboration began in the mid-1980s when Sir Ravinder, as head of the Kennedy Institute of Rheumatology at Imperial College, recruited Feldmann. Their in vitro studies showed that blocking TNF-α with antibodies prevented IL-1 production, revealing TNF-α to be a master regulator of cytokine activity. In 1989, they demonstrated that biopsies of human synovium showed TNF-α receptors to be upregulated in RA at the height of disease. And by 1992, clinical trials with a TNF-αmonoclonal antibody — performed against a backdrop of skepticism from both industry and academia — yielded powerful results that led to the development of three anti-TNF drugs, infliximab, etanercept, and adalimumab, which are effective in most RA patients and can protect joints from further destruction. “We grew with that field,” Sir Ravinder told the JCI. “We were on the ground floor when cytokine cDNAs were cloned by industry, and we had access to these probes to find out which cytokines were expressed in joints and so on. So we were children of circumstance.” Feldmann and Sir Ravinder talk about each other’s contributions as much as each does his own. Feldmann calls Sir Ravinder “an excellent clinician and good administrator” and describes himself as “strong on science and finding commercial partners for ventures,” while Sir Ravinder explains that the partnership works because “our knowledge base and expertise is overlapping and in different areas. We have found that with Marc being more deeply engrossed as a full-time laboratory researcher in the lab side of things, and me with one foot in the lab and one in the clinic, there has been an overarching continuum of expertise which we needed to take things from bench to the bedside. At the personal level, we like and complement each other in our character.” Although Sir Ravinder retired last year, their collaboration seems unbreakable. Last October, Feldmann succeeded him to become director of the Kennedy Institute. They are now keen to recruit young blood. “The demographics of the British academic system are quite old,” Feldmann says. “People don’t have the chance to work independently at an early age. So we’re currently recruiting four lecturers to work as team leaders.” Sir Ravinder has an emeritus position and still comes into the institute. He says, “We will still probably discuss things that will allow the next generation of investigators to take this work further.” Among other endeavors, Sir Ravinder and Feldmann plan to resolve issues regarding anti-TNF therapy. For example, why do 30% of patients not respond to treatment? Sir Ravinder offers an answer. “One of the interesting things about RA is that it’s a disease characterized by periodic exacerbation and relative quietness. I think there is some kind of underlying trigger, which we don’t understand, acting in a pulsatile fashion and recurringly exhibiting itself. I suspect what’s happening in the 70% that respond is that you’re catching them in a stage when it’s been triggered again, and the other 30% could be in a stasis phase which is independent of TNF. So I think there’s a dynamic to this process that we haven’t fully understood. I want to discuss these crazy ideas with younger people and encourage them to think of ways of investigating this kind of thing. Marc’s group is now very interested in looking at whether T cells are playing such a role.” What does winning the Lasker Award mean to them? “It’s too early to say what effect it will have on our work,” says Feldmann. “The nice thing for me,” says Sir Ravinder, “is that it’s come at a stage in my career when I don’t feel I need to gain any Brownie points. So I hope it allows me to encourage this field of research, especially the transitional area where you need to make sure that young people who are clinically qualified and scientifically well trained realize that this is a very rewarding thing to be doing.”

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

The Role of Perception of Pain and Functional Disability in Predicting Ruminant Intellectual Women with Rheumatoid Arthritis

Introduction Rheumatoid arthritis is the most common inflammatory disease of the joints and in addition to physical disability, mental disorders are very common in these patients. mental rumination is one of the problems that patients with rheumatoid arthritis face, and one of the factors that has a great impact on it is the perception of pain and functional dysfunction of patients. Therefore,...

متن کامل

Hearing status in patients with rheumatoid arthritis

Background: Previous studies showed that one of the complications of rheumatoid arthritis disease was auditory disorder. The goal of the present study was to compare the auditory status in patients with rheumatoid arthritis and healthy individuals. Methods: In the present case-control study, 30 normal persons and 60 persons with rheumatoid arthritis with mean age of 46.72 and standard deviatio...

متن کامل

Comparing bone mineral density in rheumatoid arthritis and psoriatic arthritis

Background: Changes in patients’ bone mineral density (BMD) is one of the problems in patients with rheumatoid arthritis, which can be due to the use of corticosteroid drugs to reduce patients' symptoms or due to the aging process in patients. In this study, we decided to compare BMD in patients with psoriatic arthritis and rheumatoid arthritis. Methods: This study as a cross-sectional descrip...

متن کامل

The Relationship between Porphyromonas gingivalis and Rheumatoid Arthritis: a Cross-Sectional Clinical, Microbiological, and Molecular Approach

Background: The relationship between rheumatoid arthritis and poor oral hygiene has longbeen proven. Colonization of Porphyromonas gingivalis in the oral cavity can play an important role in rheumatoid arthritis. The aim of this study was to determine whether there is a relationship between rheumatoid arthritis disease and the presence of P. gingivalis. <stro...

متن کامل

Relationship between Pain-Related Beliefs and Pain Anxiety with Depression in Patients with Rheumatoid Arthritis

 Aims and background: Chronic pain has many emotional and psychological pressures and is a complex psychological experience. The purpose of the study was to investigate the relationship of pain-related beliefs and pain anxiety with depression in patients with rheumatoid arthritis. Materials and methods: It was a descriptive-correlational study thus, among patients with rheumatoid arthritis in E...

متن کامل

Effects of Rheumatoid Arthritis on the Larynx

Introduction: The aim of the present study was to compare the videolaryngostroboscopic findings between patients with rheumatoid arthritis and vocally healthy controls.   Materials and Methods: This case-control descriptive study was performed on 113 people, including 50 patients with rheumatoid arthritis and 63 controls. The participants were subjected to videolaryngost...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • The Journal of clinical investigation

دوره 112 8  شماره 

صفحات  -

تاریخ انتشار 2003