Science and Technology

Understanding Covid-19’s autoimmunity after-effects

K Bharat Kumar | Updated on February 14, 2021

Covid-19, as we know, is the virus infection that affects the respiratory system. But that’s not the only part of the body that’s vulnerable. In its trail, the virus leaves behind the danger of multi-organ damage, by triggering ‘autoimmunity’ — a condition in which the body’s defence mechanism attacks its own organs, mistaking them as foreign invaders.

Vani Janakiraman, assistant professor, department of biotechnology, IIT-Madras, says globally there have been clinical reports of autoimmune conditions that follow Covid-19, suggesting a link between the two. Multiple studies have documented neurological damage in patients affected by Covid-19.

The reason for multi-organ damage need not be multi-organ infection. Even though the damaged tissues possess the proteins that facilitate the entry of the virus and subsequent infection, these proteins are not sufficient to cause the organ damage do so. Therefore, the damage may not be due to infection. Hence, there may be some yet unidentified mechanism by which the proteins on the damaged tissue trigger damage in uninfected tissues.

What happens is ‘molecular mimicry’, which occurs when virus epitopes (see box) elicit an antibody response.

Because these epitopes are similar to the ones present in the other ‘good’ proteins in the body, the antibodies could attack the latter instead of (or in addition to) the viral epitopes. This gives rise to what we know as autoimmune conditions. It is also not clear what causes the delayed onset of these conditions, well after the virus has run its course in the body.

Based on this bank of knowledge that had been building up ever since the virus began devastating populations, Prof Janakiraman and her team predicted autoimmunity as the basis of multi-organ effects of Covid-19.

She selected some experimentally verified viral epitopes found on the spike proteins of the SARS-CoV-2 virus and compared them with human autoimmunity-related proteins, using bioinformatics tools. The team started out with a set of viral epitopes and compared them only with those human proteins that were previously known to be involved in typical autoimmune conditions. From the comparison, the researchers arrived at a list in which four proteins stood out.

Human proteins housing amino acid sequences similar to the viral epitopes were identified as possible ‘autoantigens’ — that is, targets of antibodies generated against the spike protein of SARS-CoV-2.

The team’s report in the Journal of Infectious Diseases includes four such proteins involved in diseases like Guillain Barre Syndrome, neuromyelitis optica and myasthenia gravis. These autoantigens are relevant to neurological conditions occurring at the same time as Covid-19, as indicated by their involvement in autoimmune disorders with neurological symptoms. Three of these autoantigens (HSPA5, Titin, RYR2) were previously unreported in the context of Covid-19. The team also found the involvement of the fourth protein (HSP90AB1) in these disorders, but information about this protein had been previously reported.

If confirmed experimentally, the findings would contribute to the understanding and better management of post-infection autoimmune reactions. Significantly, they will also aid in vaccine design such that they avoid generating antibodies that may act against the host in any way.

Pathogens are micro-organisms such as bacteria and viruses that attack our bodies, causing diseases.Antigens are proteins on the surface of the pathogens, whose presence rings the alarm bell, triggering the body’s defence mechanism. The defence mechanism is the army of antibodies — Y-shaped proteins that lock on to the invaders, engulf and destroy them. Antibodies are also called ‘immunoglobulins’, though there are some technical differences between the two. The part of the antigens that antibodies latch on to is called the ‘epitope’. Autoantigens are ‘self’ antigens that belong to the body but still trigger an immune response, leading to autoimmunity diseases.

    Published on February 14, 2021

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