Extrafollic B cell pathway-ScienceDaily

Their findings show a test that can isolate some COVID-19 patients who require immune-calming treatment from others who may not. They may also begin to explain why some people infected with SARS-CoV-2 experience adverse results in producing abundant antibodies to the virus.

Results published online on October 7th Nature immunology..

Emory team results show recent findings by other researchers who have found that high inflammation of COVID-19 can disrupt the formation of germinal centers, the structure of the lymph nodes in which antibody-producing cells are trained. Is converging. The Emory group observed that B cell activation proceeded along an “extrafollicular” pathway outside the germinal center-looks similar to that observed in SLE.

B cells represent a library of antibody blueprints that the immune system can use to fight infection. In severe COVID-19, the immune system effectively pulls library books off the shelves and throws them into chaotic mountains.

Prior to the COVID-19 pandemic, co-authors Ignacio (Iñaki) Sanz, MD and his lab focused on SLE research and how the disease disrupts B cell development. I was guessing.

Sanz is the Head of Rheumatology at the School of Medicine, Director of the Lowance Center for Human Immunology, and Georgia Research Alliance Eminent Scholar. Co-lead author Francis Eunhyeon Lee, MD, is an associate professor of medicine and director of Emory’s Asthma / Allergy and Immunology Program.

“We came fairly fairly,” says Sanz. “We noticed that even the third or fourth ICU patients we analyzed cells had a pattern that was very reminiscent of acute flare in SLE.”

In people with SLE, B cells are abnormally activated, usually avoiding the checks and balances that constrain them. It often leads to the production of “autoantibodies” that react to cells in the body, causing symptoms such as malaise, joint pain, skin rashes, and kidney problems. Flare is the time when symptoms worsen.

Whether severe COVID-19 causes autoantibody production and has clinical consequences is currently under investigation by the Emory team. Sanz says other researchers have observed autoantibodies during the acute phase of the disease and whether long-term autoimmune reactions are associated with fatigue, arthralgia, and other symptoms experienced by some survivors. It states that it is important to understand.

“It’s an important question that needs to be addressed through careful long-term follow-up,” he says. “Not all severe infections do this. Sepsis does not look like this.”

In lupus, extrafollicular B-cell responses are characteristic of African-American patients with severe illness, he adds. In a new study, the majority of patients with severe infections were African-American. It is important to understand how underlying disease and health-related disparities promote the strength and quality of B cell responses in both autoimmune disease and COVID-19, Sanz said.

In this study, 10 critically ill COVID-19 patients (4 of whom died) admitted to the intensive care unit of Emory Hospital were treated as outpatients with 7 COVID-19 patients and 37 healthy controls. Compared with.

People in the severe group tended to have elevated levels of antibody-secreting cells early in the infection. In addition, B cells and the antibodies they produced showed features suggesting that the cells were activated by the extrafollicular pathway. In particular, cells received fewer mutations in the antibody gene than were normally seen in a concentrated immune response that was sharpened within the germinal center.

The· Nature immunology The paper was the result of a collaboration across Emory. The co-lead authors are Dr. Matthew Woodruff, an instructor in Sants’ lab, and Dr. Richard Ramonell, MD, Fellow of Lung and Emergency Medicine at Emory University Hospital.

Ramonell states that the patients studied were treated early in the COVID-19 pandemic. It was before the widespread introduction of the anti-inflammatory corticosteroid dexamethasone, which has been shown to reduce mortality.

The team’s findings may help discuss which COVID-19 patients should be treated with immunomodulatory treatments such as dexamethasone and anti-IL-6 drugs. Patients with greater proliferation of B cells undergoing extrafollicular activation also had higher levels of inflammatory cytokines such as IL-6.

Some patients with COVID-19 are given drugs that resist IL-6, but clinical trials have mixed results. Sanz suggests that patients with markers of an unregulated immune response may be good candidates for treatment with anti-inflammatory drugs that target the corresponding pathways.

This study is supported by the National Institute of Allergy and Infectious Diseases (U19AI110483-Emory Autoimmune Center of Excellence, P01AI125180, R37AI049660, R01AI121252, U01AI141993), the National Institute on Aging (R01AG054991), and the National Institute of Cardiopulmonary Blood (T32HL116271). I did. ).