Longevity Briefs: Remission Of Three Autoimmune Diseases With A Single Treatment

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Autoimmune diseases are the result of the immune system erroneously attacking the body’s own cells and tissues. Lymphocytes (the group of white blood cells that include T and B cells) are the ‘precision weapons’ of the immune system that identify antigens (specific molecules that are unique to a given pathogen). It is normal for the immune system to sometimes accidentally produce a lymphocyte that recognises an antigen present on human cells, but there are multiple layers of protection in place to ensure that such lymphocytes are destroyed. If you are unlucky enough that such a cell survives, and said cell then comes into contact with the antigen it recognises, it will divide and initiate an immune response targeting any cells carrying that antigen, resulting in autoimmune disease. It is not entirely clear if some autoimmune diseases have a specific trigger. Autoimmune diseases also become more common with advancing age for a variety of reasons.

Most autoimmune diseases require lifelong management to prevent flare-ups, as there is currently no way to make the immune system ‘forget’ the antigen it is mistakenly targeting. Unfortunately, some people don’t respond well to conventional therapies, leaving them with limited treatment options and significantly reduced quality of life. This was the case for the subject of this case study: a 47 year-old woman with three different autoimmune diseases who had not responded well to any treatment in the decade since she was diagnosed.

The discovery:

The patient in question had three autoimmune diseases: autoimmune haemolytic anaemia (AIHA), in which the immune system attacks red blood cells; immune thrombocytopenia (ITP) in which the immune system destroys platelets that are involved in clotting; and antiphospholipid antibody syndrome (APS), in which the immune system produces antibodies that can trigger the formation of dangerous blood clots. This required her to have daily blood infusions to replace the red blood cells that were being destroyed, as well as taking medication to prevent blood clots from forming.

Having exhausted all conventional treatments such as steroids, doctors turned to an experimental approach called CD19-directed CAR-T cell therapy. CAR-T cells (chimeric antigen receptor T cells) are a form of white blood cell that have been genetically engineered to target a specific antigen. They are most known for their use in cancer immunotherapy, in which they can be programmed to recognise antigens on the surface of cancer cells and kill them. In this case, CAR-T cells were engineered to recognise CD19, a protein that is expressed on the surface of B cells. B cells play an important role in most autoimmune diseases. They not only produce the antibodies that attack the patient’s own tissues, but also help to sustain the autoimmune response by presenting antigens to T cells (they are involved ‘telling’ the rest of the immune system what to attack).

The idea was that these CD19-directed CAR-T cells would destroy most of the patient’s B cell population, which would then be regenerated over time from fresh, non self-reactive cells produced in the bone marrow – essentially resulting in a ‘reset’. This strategy worked remarkably well – the patient stopped requiring blood transfusions within 7 days, and her haemoglobin levels became normal within 25 days. Her other two autoimmune diseases also stabilised without the need for additional treatments. Months after treatment, when B cells had been repopulated, it was found that most of these B cells were naive, meaning they were cells that had not yet been activated by any antigen, suggesting that a ‘reset’ of sorts had been achieved. It has now been a year since the treatment was given, and the patient still does not require blood transfusions or other treatment, and is living a mostly normal life.

The implications:

This case report suggests that CD19-directed CAR-T cell therapy has the ability to reset B cell populations and achieve lasting remission in autoimmune disease that is resistant to treatment. This could be an enormous breakthrough for the treatment of such cases, but since this was a case study with a sample size of one, some caution is advised. While CAR-T undoubtedly worked in this case, we don’t know whether it would work as well in other diseases or how frequently it would work in similar cases. There are also risks associated with CD19-directed CAR-T therapy, including lasting damage to the immune system, damage to the bone marrow (which this patient experienced, though this could have been due to previous unsuccessful treatments) and potential neurotoxicity (of which there was no evidence in this case). Those are reasonable risks when other treatments have failed, but it’s going to be a while before this kind of approach is considered as a regular option for autoimmune diseases, especially considering the high costs of CAR-T therapy.