Swiss researchers from the Institute of Medical Virology identified a significant link between autoantibodies and interferon and a decrease in the body’s antiviral defenses. Elderly individuals often have autoantibodies that block the action of type I interferons (IFN), essential immune system proteins that help combat viruses. These autoantibodies can increase the risk of severe infections, including COVID-19, influenza, and herpes.
To study how these autoantibodies against IFN-I develop and their consequences, scientists used data from the Swiss HIV Cohort Study (SHCS). SHCS contains plasma and cell samples from over 21,000 patients since 1988. Around 60% of this cohort are people over the age of 50. Additionally, in this cohort, IFN-I therapy was widely used to treat the hepatitis C virus before direct-acting antiviral drugs became available. Researchers traced the development of autoantibodies over decades, finding that their presence reduces the effectiveness of innate immunity.
Autoantibodies Against Type I Interferons in the Elderly
The study included 1,876 people over 65 tested for autoantibodies (autoAbs) against type I interferons. Results showed:
- 1.17% of patients had neutralizing autoAbs against at least one type of interferon: IFNα2, IFNβ, or IFNω.
- These antibodies spread more among patients aged 70-79, at 1.68%.
- 0.69% of patients had non-neutralizing autoantibodies that bind to IFN-I but do not entirely block their action.
- Men were more frequently affected, accounting for 94.3% of identified cases.
Autoantibodies Against IFN Develop Around Age 60-65 and Persist for Life
Researchers selected 70 individuals: 35 with autoAbs to IFN-I and 35 without them. Plasma samples collected over more than 20 years were available for these patients.
AutoAbs to type I interferons were absent throughout the patients’ lives but began developing around 60-65. At various times, some patients developed autoAbs against different interferons (IFNα2, IFNβ, and IFNω). A few patients had autoAbs only against one type of interferon.
A specific acute event, such as an infection, triggered the emergence of autoantibodies. The autoAbs remained detectable in subsequent plasma samples. Binding autoAbs gradually increased in titer for anti-IFNα2 and anti-IFNω but not for anti-IFNβ.
Neutralizing AutoAbs Against IFNα2 Are Linked to Hospitalization Due to COVID-19 and Disruption of IFN-Stimulated Gene Levels
The presence of neutralizing autoAbs against type I interferons is associated with more severe cases of COVID-19. Patients with these autoAbs had reduced interferon-stimulated genes (ISG) levels, weakening the body’s innate antiviral defense. Thus, autoAbs to IFN-I can significantly increase susceptibility to viral infections, particularly in older age.
Development of Neutralizing AutoAbs Against IFNα May Have Long-Term Consequences
The link between neutralizing autoAbs against IFNα and severe COVID-19 in some patients has been observed for a decade after the first detection of these autoAbs.
Previous Viral Infections May Influence the Development of AutoAbs to IFN-I
The development of autoantibodies against IFN-I may be associated with previous viral infections, such as shingles. In a sample of 35 patients with autoAbs and 138 without, scientists found that people with autoAbs were more likely to have had herpes, although a direct link to an acute infection was not always evident. For example, in 10 of 12 patients with autoAbs, shingles had been diagnosed 3-14 years before the appearance of autoantibodies to IFN-I.
In rare cases, autoAbs may appear after severe viral infections. One patient developed autoAbs after pneumonia caused by influenza, while another developed them following hepatitis C treatment with interferon.
Autoimmune Diseases Can Trigger the Development of AutoAbs Against IFN-I
By examining data from 11 patients with elevated levels of autoantibodies associated with autoimmune diseases—such as autoAbs against SSA and SSB, characteristic of Sjogren’s syndrome—researchers found that 100% of patients later developed autoAbs against IFN-I. Moreover, patients testing positive for antinuclear antibodies (ANA) were significantly more likely to create autoAbs against IFN-I.
AutoAbs Against IFN-I May Develop After Exposure to Very High Levels of IFN-I
One particular case involved a patient who developed neutralizing autoAbs against IFNα after treatment for hepatitis C with IFNα. This is a rare occurrence: only 3 out of 300 people were found to have autoAbs after IFNα treatment, and only one developed neutralizing autoAbs. Preexisting self-tolerance issues, present before interferon treatment, play a vital role in the formation of autoAbs.
Conclusion
Around 1.9% of elderly patients living with HIV develop autoantibodies against type I interferons, weakening their antiviral defenses. The development of autoAbs against IFN-I typically begins around age 60-65. Patients with autoantibodies show reduced ISG gene activity, compromising their antiviral protection. These autoantibodies neutralize IFN-I, increasing susceptibility to severe viral infections, including COVID-19. Most patients with these antibodies also show a predisposition to autoimmune diseases.
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