Antibodies – for better or worse

Monoclonal antibodies can potentially have widespread application and will likely become even more common in the future. Sandra Kleinau, Professor …

Immune cells protect us from contagions and keep us healthy, but sometimes they mistakenly attack our own bodies in autoimmune diseases. There are still no cures for autoimmune diseases, but, in my research team, we are studying how monoclonal, or cloned, antibodies can be used to tailor individual treatments, writes Sandra Kleinau, professor of molecular immunology.

The COVID-19 pandemic has focused attention on immunology and many questions have arisen about antibodies against the coronavirus and testing for these. Since I have studied immune defences and antibodies throughout my career, I would like to take this opportunity to provide an immunologist’s perspective on how antibodies generally occur with an infection.

During an infection, B and T lymphocytes or cells are activated, which specifically recognise disease-causing substances, such as a virus. The B cells produce specific antibodies, proteins that can neutralise and take care of the virus so that it cannot infect new cells. During an infection, B memory cells are also formed that remember the virus and can be activated to provide protection against new infections if the individual comes into contact with the virus again.

Sandra Kleinau, Professor of Molecular

Immunology. Photo: Mikael Wallerstedt

If we translate this to the new viral disease COVID-19, we can assume that regardless of whether you have had mild or severe symptoms of COVID-19, you will have antibodies for the virus. There are different versions of the antibodies, such as IgM and IgG, and these can be diagnosed through blood tests. These tests can have different degrees of sensitivity in detecting antibodies. This means that certain tests can analyse very small amounts of antibodies in the blood while others need large amounts to confirm the presence of the antibodies. This can help explain those reports describing people who have had COVID-19 but who have not developed antibodies against the virus. If you have been sick with COVID-19 and recovered, you will likely have antibodies circulating in your blood for some time. We do not yet know how long this is the case, but generally you have lifelong immunity if you have had and recovered from a viral disease.

But antibodies are not always beneficial. With an autoimmune disease, B cells often form that mistakenly produce antibodies against the body’s own proteins and tissues. Large amounts of these autoantibodies can lead to your own body being attacked and result in chronic inflammation. Depending on which structures the antibodies react against, different autoimmune diseases can occur. For example, rheumatoid arthritis affects the joints.

For several years, my research team has studied how specific Fc receptors on immune cells recognize and bind to structures on antibodies that are bound to the body’s own proteins. An inflammation occurs when these Fc receptors are activated. We still lack a cure for autoimmune diseases, but we have good potential for treating them with anti-inflammatory and immune-depressing medications. Several of these medications consist of antibodies, more specifically monoclonal or cloned antibodies that are more specific than traditional medicines and have fewer side effects. The use of monoclonal antibodies as a biological medication has been successful and is widespread today, not just for autoimmune diseases but also for treatment of cancers and infections.

Antibodies can be produced against most disease-causing molecules and cells. By binding to these molecules, the antibodies help the patient’s immune defences render them harmless. In addition to the different antibodies, different variations of antibodies can be produced. So instead of using a “one-size-fits-all” approach, my research team is currently studying if we can advance immunotherapy with monoclonal antibodies by tailoring treatment for the specific patient. Matching the patient’s Fc receptor pattern with appropriate variations of therapeutic antibodies can be a possible way of enhancing the effect of immunotherapy. Monoclonal antibodies can potentially have widespread application and will likely become even more common in the future.

Sandra Kleinau, Professor of Molecular Immunology at Department of Cell and Molecular Biology, Uppsala University