By snipping out and analyzing tiny samples of patients' tonsils, scientists have identified a key cellular checkpoint that is somehow bypassed in lupus patients, where harmful immune cells that normally are squelched by the body are mistakenly granted access.
The in-depth look at tissue from a person's tonsils, a technique seldom used to study the immune system, has provided doctors with key information about just what goes wrong in patients with lupus to cause their immune systems to attack themselves, causing symptoms like joint pain, fatigue, and other complications like kidney failure.
The paper detailing the work by immunologists and rheumatologists at the University of Rochester Medical Center will be in the November issue of the Journal of Clinical Investigation.
"Tonsils are very informative," said Ignacio Sanz, M.D., professor of Medicine, Microbiology & Immunology, and chief of the Division of Clinical Immunology and Rheumatology, who led the study. "Peripheral blood doesn't have the organization you need to really understand the immune system. The tonsils give us a window into the immune system that we didn't have before."
The tonsils are made up of lymphoid tissue and help the body fight off infection. But unlike the spleen, a major organ that plays a key role in the immune system, doctors can take a small biopsy of the tonsils, getting a look at structures that are present there but not in the blood, which is studied more commonly.
Sanz's team focused on lymph structures in the tonsils known as germinal centers, where teeming masses of immune cells known as B cells and T cells glom together and swap crucial information about invaders like bacteria and viruses. Such ongoing education is crucial to our immune system – it's how our cells are trained to recognize enemies like colds and flu, and where they learn not to attack our own bodies. Unfortunately, in diseases like lupus, diabetes, rheumatoid arthritis, and multiple sclerosis, our cells don't always learn the difference, and some immune cells become "auto-reactive" and attack our own tissues.
"Our immune system needs redundancy and adaptability to recognize and fight the antigens it needs to fight," said Sanz. "But the price we pay is a fair amount of auto-reactivity. Because of that, we need very good systems to discriminate and control auto-reactive B cells."
It's those systems, trained to recognize and then eliminate errant cells, which fail in lupus. Somehow, rogue cells – in this study, 9G4 B cells – slip through the body's defenses. Doctors have known that in people with lupus, antibodies from such cells make up a much greater percentage of the person's immune system than in healthy people. In this study the team found that lupus patients have as many as 10 times the number of such cells as healthy people in the germinal centers, sophisticated processing centers of the immune system.