Immunity: COVID-19 May Trigger a Mechanism Similar to the Development of Autoimmune Diseases

Researchers have identified the specific immune cells that may trigger the production of autoantibodies following SARS-CoV-2 infection. These antibodies can mistakenly target the body’s own tissues instead of the virus. The study was published in the journal Immunity.

Scientists from the Institute for Systems Biology (ISB) and their colleagues examined immune responses in participants of a long-term COVID-19 study. They used single-cell RNA sequencing, chromatin activity analysis, proteomics, genetic data, and laboratory experiments to track changes in B-cell activity during infection.

The researchers identified a specific type of B cell known as an atypical memory B cell as a key precursor of autoantibody-producing cells. In people with high levels of autoantibodies, these cells were particularly likely to develop into antibody-producing cells. At the same time, these patients generally had a weaker response of antibodies capable of neutralizing the virus itself.

DN2 cells, one of the major subtypes of atypical B cells, were of particular interest. Their characteristics closely resembled those of immune cells previously associated with autoimmune diseases such as systemic lupus erythematosus.

In patients with elevated levels of autoantibodies, DN2 cells showed increased activity in signaling pathways involving Toll-like receptor 7 (TLR7), as well as the transcription factors T-bet and XBP1. According to the researchers, this combination of mechanisms may prime these cells for the large-scale production of autoantibodies.

Genetic analysis also revealed a strong connection between DN2 cells and inherited susceptibility to autoimmune diseases. Of all the B-cell populations examined, DN2 cells showed the strongest association with genetic variants linked to systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, Crohn’s disease, type 1 diabetes, and primary biliary cholangitis.

The researchers suggest that SARS-CoV-2 infection may activate an immune program similar to one involved in the development of established autoimmune diseases. In people with a genetic predisposition, this may increase the likelihood of producing autoantibodies and subsequently developing autoimmune complications.

However, the findings demonstrate an immune mechanism and association rather than proving that COVID-19 directly causes autoimmune disease in every person who develops autoantibodies. Further research will be needed to determine how often these immune changes lead to clinically significant autoimmune conditions.