Researchers Uncover Gene’s Role in Rheumatoid Arthritis
News Jan 30, 2013
University of Michigan research sheds new light on why certain people are more likely to suffer from rheumatoid arthritis – paving the way to explore new treatments for both arthritis and other autoimmune diseases.
The new UMHS research in mice identifies how a specific group of genes works behind the scenes to activate the bone-destroying cells that cause severe rheumatoid arthritis, a debilitating health issue for millions of Americans.
“We believe this could be a significant breakthrough in our understanding of why certain genes are associated with higher risk of rheumatoid arthritis and other autoimmune diseases – a link that has been a mystery in the field for decades,” says lead author Joseph Holoshitz, M.D., professor of internal medicine and associate chief of research in the division of rheumatology at the U-M School of Medicine.
“We hope that this improved understanding will open the door to future design of drugs to treat this crippling disease and autoimmune disease in general.”
The research appeared in The Journal of Immunology and was highlighted by Nature Reviews Rheumatology.
Rheumatoid arthritis is a chronic inflammatory disorder that damages the lining of joints and causes bone erosion, joint deformity and disability. The disease is an autoimmune disorder, characterized by the body’s immune system mistakenly attacking the body's tissues.
Researchers have long studied the phenomenon of why certain versions of an inherited group of genes known as “human leukocyte antigen” (HLA) are associated with autoimmune disorders. One subset of these HLA genes that codes a protein sequence called “shared epitope” represents the most significant genetic risk factor for rheumatoid arthritis, affecting disease susceptibility and severity. However, until now, the reason for this strong link has been unclear.
A common theory in the field has been that the association between particular HLA genes and autoimmune diseases is a result of mistakenly identifying body tissues as foreign – making the body the target of the immune system and setting off an attack on self-tissues, which results in disease.
The UMHS research challenges this long-held theory. The study shows, for the first time, how this subset of HLA genes causes arthritis – by activating inflammation-causing cells, as well as bone-destroying cells (known as osteoclasts). This leads to severe arthritis and bone erosion.
“We showed how the shared epitope is directly triggering osteoclasts, the very cells that are responsible for joint destruction in people with the disease,” says Holoshitz.
“Understanding these mechanisms at play could be a significant piece of future drug development. Because we now know the molecular mechanism that activates arthritis-causing cells, we have the potential to block that pathway with simple chemical compounds that could be used to treat rheumatoid arthritis and other diseases.”
Study Reveals How MRSA Infection Compromises Lymphatic FunctionNews
Infections of the skin or other soft tissues with the hard-to-treat MRSA bacteria appear to permanently compromise the lymphatic system, which is crucial to immune system function. Investigators describe how MRSA infection impairs the ability of lymphatic vessels to pump lymphatic fluid to lymph nodes in mouse models, which may contribute to the frequent recurrences of MRSA infection experienced by patients.
Possible Biomarker to Identify Who Would Benefit from ImmunotherapyNews
While immunotherapy has made a big impact on cancer treatment, the fact remains that only about a quarter of patients respond to these treatments. In a new study, researchers examined tissue samples from melanoma and ovarian cancer patients treated with immunotherapies and found a link between the percentage of antigen-presenting cells expressing PD-L1 and an objective clinical response to treatment.READ MORE
Fight Against Cancer: Drug Combination Helps Kickstart the Immune SystemNews
Scientists from King's College London have found a way to boost the immune system to help it fight back against cancer.
The breakthrough involves the first ever use of a combination of chemotherapy and a drug being trialled as a treatment for neonatal jaundice, that together help kick start the body's natural defences.