December 2003: A Look at the Year Behind and the Year Ahead
December 2003: A Look at the Year Behind and the Year Ahead
Editor's note: Although every year has its share of new developments, it seems that this past year has been especially busy, in many aspects of life on this planet. Medicine has been no exception.
We asked Medscape Editorial Advisory Board member Robert I. Fox, MD, PhD, to present what he thought were the most important developments in rheumatology in 2003, and what 2004 might bring. Here's what he wrote:
In the spirit of the end-of-the-year awards, such as Time's "Man of the Year" and Nature's "Molecule of the Year," it seems appropriate to nominate rheumatology's "Joint Mechanism of the Year." In recent years, we have been blessed with monumental breakthroughs in therapy such as tumor necrosis factor (TNF) inhibitors that were unexpectedly successful and brought new high levels of expectation for acceptable therapeutic response of rheumatoid arthritis patients. The past year has seen more consolidation, as the mechanisms responsibility for TNF benefit have been unraveled to yield a family of new receptors and therapeutic targets. Also, the limitations of TNF therapy in some rheumatoid arthritis patients and the relatively less dramatic benefit in other diseases, such as systemic lupus erythematosus and Sjögren's syndrome, have led to the search for additional pathways that may yield to therapeutic intervention.
Thus, the "Joint Mechanism of the Year" award goes to the study of the mechanisms that underlie the interaction of innate (non-HLA-linked) and acquired (HLA-linked) immune systems. The innate immune system is designed to immediately recognize "danger" signals, such as bacterial products (ie, lipolysaccharide) or products of apoptosis or cell death through a family of Toll-like receptors. The acquired or adaptive immune system generates a family of "memory" lymphocytes that can progressively learn from past experience to generate higher-affinity responses. During the past year, methods such as genomic and proteomic screening have suggested that molecules related to interferon type I/II signature seem to involve the interaction of the innate and acquired immune systems. We have long talked about autoimmune disease as the result of the interaction of genetic and environmental factors. Now, it appears that specific molecules and receptors that actually explain the mechanism of this interaction are being recognized. The goal of the next year will be to apply these lessons of molecular biology to the clinic in order to understand and predict our failures as well as our successes with anti-TNF therapy.
The runner up, in a close vote, was the increased recognition of the B cell, which has languished in the shadow of the T cell during the past decade. We originally started out with autoantibodies as the hallmark of our immune disease, but seemingly lost interest as HLA-DR associations drove us to beat the T cells into immunologic submission. The finding that anti-B-cell antibodies may have an important role not only in some rheumatoid arthritis patients but also in other diseases, such as systemic lupus erythematosus, may lead to a wider understanding of B-cell regulation.
In The Onion category, we nominate the failure of rheumatologists to form a consensus on fibromyalgia. Rheumatologists are faced with a real dilemma. The attitudes towards fibromyalgia as a discrete entity keep swinging like a pendulum. However, the mechanisms of "sick brain" syndrome that are under intensive investigation in disorders such as multiple sclerosis or even aging have not been carefully studied by rheumatologists. Hopefully, the mechanisms of genetics and cytokines developed by neurochemists will be studied in rheumatology patients during the next year.
Robert I. Fox, MD, PhD
Member
Rheumatology and Medicine Department
Scripps Memorial Hospital
La Jolla, California
Editorial Advisory Board Member
Medscape Rheumatology
We'd like to know what you thought the highlights in rheumatology were in 2003, and what you might expect in 2004. Post your thoughts and read others' ideas in this Open Forum Discussion topic.
Editor's note: Although every year has its share of new developments, it seems that this past year has been especially busy, in many aspects of life on this planet. Medicine has been no exception.
We asked Medscape Editorial Advisory Board member Robert I. Fox, MD, PhD, to present what he thought were the most important developments in rheumatology in 2003, and what 2004 might bring. Here's what he wrote:
In the spirit of the end-of-the-year awards, such as Time's "Man of the Year" and Nature's "Molecule of the Year," it seems appropriate to nominate rheumatology's "Joint Mechanism of the Year." In recent years, we have been blessed with monumental breakthroughs in therapy such as tumor necrosis factor (TNF) inhibitors that were unexpectedly successful and brought new high levels of expectation for acceptable therapeutic response of rheumatoid arthritis patients. The past year has seen more consolidation, as the mechanisms responsibility for TNF benefit have been unraveled to yield a family of new receptors and therapeutic targets. Also, the limitations of TNF therapy in some rheumatoid arthritis patients and the relatively less dramatic benefit in other diseases, such as systemic lupus erythematosus and Sjögren's syndrome, have led to the search for additional pathways that may yield to therapeutic intervention.
Thus, the "Joint Mechanism of the Year" award goes to the study of the mechanisms that underlie the interaction of innate (non-HLA-linked) and acquired (HLA-linked) immune systems. The innate immune system is designed to immediately recognize "danger" signals, such as bacterial products (ie, lipolysaccharide) or products of apoptosis or cell death through a family of Toll-like receptors. The acquired or adaptive immune system generates a family of "memory" lymphocytes that can progressively learn from past experience to generate higher-affinity responses. During the past year, methods such as genomic and proteomic screening have suggested that molecules related to interferon type I/II signature seem to involve the interaction of the innate and acquired immune systems. We have long talked about autoimmune disease as the result of the interaction of genetic and environmental factors. Now, it appears that specific molecules and receptors that actually explain the mechanism of this interaction are being recognized. The goal of the next year will be to apply these lessons of molecular biology to the clinic in order to understand and predict our failures as well as our successes with anti-TNF therapy.
The runner up, in a close vote, was the increased recognition of the B cell, which has languished in the shadow of the T cell during the past decade. We originally started out with autoantibodies as the hallmark of our immune disease, but seemingly lost interest as HLA-DR associations drove us to beat the T cells into immunologic submission. The finding that anti-B-cell antibodies may have an important role not only in some rheumatoid arthritis patients but also in other diseases, such as systemic lupus erythematosus, may lead to a wider understanding of B-cell regulation.
In The Onion category, we nominate the failure of rheumatologists to form a consensus on fibromyalgia. Rheumatologists are faced with a real dilemma. The attitudes towards fibromyalgia as a discrete entity keep swinging like a pendulum. However, the mechanisms of "sick brain" syndrome that are under intensive investigation in disorders such as multiple sclerosis or even aging have not been carefully studied by rheumatologists. Hopefully, the mechanisms of genetics and cytokines developed by neurochemists will be studied in rheumatology patients during the next year.
Robert I. Fox, MD, PhD
Member
Rheumatology and Medicine Department
Scripps Memorial Hospital
La Jolla, California
Editorial Advisory Board Member
Medscape Rheumatology
We'd like to know what you thought the highlights in rheumatology were in 2003, and what you might expect in 2004. Post your thoughts and read others' ideas in this Open Forum Discussion topic.
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