‘Ubiquitous’ COVID-19 may help rheumatologists understand integrated immune response
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SCOTTSDALE, Ariz. —The COVID-19 pandemic could enable better understanding of the relationship between infection and autoimmunity, according to a speaker at the Basic and Clinical Immunology for the Busy Clinician symposium.
“Integrated immune response is a balance,” Leonard Calabrese, DO, RJ Fasenmyer Chair of Clinical Immunology at the Cleveland Clinic, and chief medical editor of Healio Rheumatology, told attendees. “On one hand, we have effector mechanisms cells, cytokines, chemokines, working in a type of concert that generate an inflammatory response that, when effective, is controlled. On the other side, there are these tolerogenic and regulatory forces which are critical; that is why every time you get a cold, you don’t develop lymphoma from an unbridled immune response.”
The pervasiveness of the COVID-19 pandemic has provided researchers with ample opportunity to understand these immune responses.
“The SARS-CoV-2 pathogen is ubiquitous,” Calabrese said. “We are exposed to it time again and time again.”
The rheumatology community has long discussed viral hypotheses to explain the pathogenesis of rheumatic and autoimmune diseases, according to Calabrese; for example, while the association between Epstein-Barr virus has been established, questions remain.
“EBV and lupus has been a tantalizing area of research, but has not been explained in a three-dimensional way,” he said.
What is known is that upon contact with a pathogen, the innate immune system serves as an “early warning system” and “comes to the fore,” noted Calabrese. But there are still many unknowns about how the innate immune response transitions to the adaptive immune response. The lack of understanding surrounding these responses was highlighted by the unpredictability of COVID-19 infection in any given individual.
“We still do not understand why one person does not develop it and another does,” Calabrese said.
Digging deeper, Calabrese discussed two broad categories of potential triggers of immune response: pathogen-associated molecular patterns and damage-associated molecular patterns. “This has been a good and workable paradigm,” he said.
Part of that response/paradigm includes the interferon response, which has been observed in SARS-CoV-2 infection as well as in many rheumatic and autoimmune diseases.
“Interferon response has been the focus of tremendous interest in rheumatology,” he said. “When young, healthy people die from COVID-19, many of them had heterozygous mutations in the type 1 interferon pathway.”
Complicating the picture is that, depending on the situation, interferon can serve as a “friend or foe,” according to Calabrese. “Interferon is friendly if it is stopping the coronavirus in our nose,” he said. “It is very unfriendly if its unleashed and unbridled, as it can contribute both to cytokine storm and development of autoimmunity.”
Investigators are currently studying both the positive and negative effects of interferon in the context of SARS-CoV-2 infection and autoimmunity. It is clear that when the virus occurs, autoantibodies are generated. What is not clear is whether that necessarily translates into the generation of immunologic diseases, according to Calabrese. “This is going to be one of the interesting stories for the next number of years,” he said.
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Calabrese L. Lessons from COVID 19 on How to Understand the Integrated Immune Response in 2024. Presented at Basic and Clinical Immunology for the Busy Clinician, Feb. 17-18, 2024; Scottsdale, Arizona (hybrid meeting).
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