04 Nov Some DNA Variants Raise Risk of Lupus But Protect Against Severe COVID

MedicalResearch.com Interview with:

Professor Tim Vyse
Professor of Molecular Medicine and
Dr David Morris
Non Clinical Lecturer in Molecular Genetics
Guy’s Hospital, London

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We observed a correlation between the genetic associations with severe COVID-19 and those with systemic lupus erythematosus (SLE, Lupus), and aimed to discover which genetic loci were shared by these diseases and what biological processes were involved. This resulted in the discovery of several genetic loci, some of which had alleles that were risk for both diseases and some of which were risk for severe COVID-19 yet protective for SLE.

The locus with most evidence of shared association (TYK2) is involved in interferon production, a process that is important in response to viral infection and known to be dysregulated in SLE patients.  Other shared associated loci contained genes also involved in the defense response and the immune system signaling. These results add to the growing evidence that there are alleles in the human genome that provide protection against viral infection yet are risk for autoimmune disease.

MedicalResearch.com: What should readers take away from your report?

Response: The relationship between Lupus risk and COVID-19 outcome is complex with multiple areas of the genome being involved in altering risk for Lupus and COVID, some of which are shared. A few DNA variants were found to be risk for both diseases, whereas others were protective for severe COVID-19, yet risk for Lupus.  The genes in the areas that of the genome that increased risk of Lupus and protected against severe COVID-19 are involved in a process known as interferon production. The immune system’s use of interferon is important in response to viral infection and known to be abnormally regulated in several autoimmune diseases, including lupus.

This is an exciting result made possible by the large genetic studies in COVID-19 and Lupus, and opens the door to our understanding of how the biology of the immune system is calibrated to protect us against infection from viruses and other infectious agents, but at the risk of developing autoimmune disease

MedicalResearch.com: What recommendations do you have for future research as a results of this study?

Response: An understating of the link between autoimmune disease and the risk of infectious disease will be improved by comparing large genetics studies of SLE and other autoimmune disease with genetic studies of other infectious diseases.  Studies in the genetics of infectious diseases are challenging due to the strong environmental component to risk.  However, population-based surveys detailed experiences with common infectious disease should provide valuable information.

The prevalence of SLE and severe COVID-19 varies over ancestry and sex. Larger studies in non-Europeans in both diseases are required to address cross ancestry differences. Studies on African populations will help identify specific genetic polymorphisms causal for both diseases in areas of the genome that we have identified as association yet are unable to explore in high enough resolution due to correlation in the genome, an issue that is helped by increasing diversity in samples for genetic association studies.

SLE is more prevalent in females while COVID-19 shows higher rates of infection and serious disease in males. Studies focused on sexual dimorphism in disease will help understand the causes of these two disease and others where a sex bias is observed.

MedicalResearch.com: Is there anything else you would like to add? Any disclosures?

Response: The relationship between infectious disease and autoimmune disease risk has long been debated, but a clear answer unforthcoming, to date.  The pandemic nature of COVID has allowed scientists to study this question in a robust and meaningful way.  The results of this study are strong evidence that there are genes in the human genome that provide protection against viral infection, but they do this at the expense (in a Darwinian sense) of being risk factors for autoimmune disease.  Is this one explanation for why autoimmune diseases have persisted in the human population?

Citation:

 Wang Y, Guga S, Wu K, Khaw Z, Tzoumkas K, Tombleson P, et al. (2022) COVID-19 and systemic lupus erythematosus genetics: A balance between autoimmune disease risk and protection against infection. PLoS Genet 18(11): e1010253. https://doi.org/10.1371/journal.pgen.1010253

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Last Updated on November 4, 2022 by Marie Benz MD FAAD