New drug target for immune diseases discovered

ScienceDaily (Aug. 4, 2010) —Researchers from Mount Sinai School of Medicine have found a newmechanism that explains how certain immune cells are activated to createprotective antibodies against infections or pathological antibodiessuch as those present in autoimmune diseases like lupus and rheumatoidarthritis.
The research is published online in Nature Immunology.
Led by Dr. Andrea Cerutti, MD, Professor of Medicine at Mount SinaiSchool of Medicine, researchers studied human tissue and immune cellsfrom people with mutations of TACI and MyD88, two proteins required toactivate the immune system. MyD88 is a signaling protein that alerts theso-called innate immune system -- the immune system encoded at birththat remains unchanged -- to the presence of pathogens. TACI is areceptor protein used to activate immune cells in the so-called adaptiveimmune system, a more sophisticated immune system than the innate,which is dynamic and combats pathogens. These new studies providedimportant and unexpected new insights in our understanding of immunediseases such as immunodeficiencies and autoimmune disorders.
"Our research shows that TACI and MyD88 are part of an immune circuitthat bridges the innate and adaptive immune systems. This circuit makesour immune response more flexible, allowing a more effective generationof protective antibodies during infections. Genetic defects of TACI andMyD88 cause immunodeficiencies characterized by recurrent,life-threatening infections. On the other hand, an abnormally strongTACI-MyD88 interaction may exacerbate autoimmune diseases like lupus orrheumatoid arthritis," said Dr. Cerutti, lead investigator of the study."Previous studies had suggested an involvement of TACI and MyD88 inlupus. Now that we have identified this interaction, we can figure out away to inhibit it and prevent these diseases from getting worse."
Autoimmune diseases like lupus and rheumatoid arthritis arecharacterized by exaggerated production of molecules that activate theadaptive immune system and abnormal antibodies, which attack normalcells causing inflammation and tissue damage. This exaggeratedproduction may occur partly as a result of abnormally strong signalingfrom TACI via MyD88. By analyzing cells and tissues from immunodeficientpatients and genetically engineered mice, Dr. Cerutti's team found apreviously unknown interaction between TACI and MyD88 that is importantfor the production of antibodies against infectious agents. Yet, thesame interaction may cause the exaggerated immune response in peoplewith autoimmune diseases.
"Our discovery provides a novel specific target, the signalingpathway between TACI and MyD88, to block the overreaction of the immunesystem and tissue damage in individuals with autoimmune disorders," saidDr. Cerutti. "We look forward to studying this discovery further anddeveloping therapeutic targets that will inhibit the interaction betweenTACI and MyD88, preventing autoimmune diseases from progressing withfewer side effects than currently prescribed treatments."
Dr. Cerutti's team collaborated with other researchers at Mount SinaiSchool of Medicine, including Charlotte Cunningham-Rundles, MD,Professor of Medicine and Pediatrics, and Huabao Xiong, PhD, AssistantProfessor of Medicine.
According to the National Women's Health Information Center,autoimmune diseases impact 23.5 million Americans. Common examplesinclude lupus, in which the immune system attacks the skin and/orseveral organs within the body; rheumatoid arthritis, in which theimmune system attacks joints; multiple sclerosis, in which the immunesystem attacks the nervous system; and Type 1diabetes, in which theimmune system attacks insulin-producing cells in the pancreas.
Editor's Note: This article is not intended to provide medical advice, diagnosis or treatment.