The alopecia areata biobank is now 4 years old and holds samples from over 100 volunteers. Since my last blog update, we have continued to use a proportion of these samples to answer questions that help to understand how the immune system causes AA. In this blog I will share details of our experiments using skin samples and explain what our findings mean. I will also share how this research has led to securing further funding to continue our research and fund the biobank for the next few years.  

What was the aim of this research? 

We know from published studies that immune cells called killer T cells attack hair follicles in people with AA, which leads to hair loss. This research laid the foundations for clinical trials which have tested JAK inhibitors for the treatment of AA. This research was extremely important for understanding how specific aspects of the immune system are involved in causing AA. However, there is still a lot we do not know about AA which limits the development of effective therapies. For instance, we do not know how other immune cells contribute to AA; this is important because we know that killer T cells cannot function in isolation. Thus, we aimed to investigate how other immune cells may be involved in causing hair loss, and how their involvement may be preventing hair regrowth in people with AA.

How did we do this?

We know that the skin is home to many immune cells which play diverse roles in the context of infection, injury, and in everyday processes that are vital for keeping the skin healthy. We therefore decided to use a technique called RNA sequencing that would allow us to obtain a broad picture of how immune cells behave in AA skin. In addition to assessing AA skin, we also collected skin biopsies from people without AA so we could compare the samples to identify changes that are specifically associated with the condition. For this experiment, we used seven scalp biopsies from people with AA and three scalp biopsies from people without AA. Before explaining RNA sequencing, I will explain what RNA is and how it can be used to understand immune activity in a tissue sample.  

Each cell in the human body contains DNA which holds information for all of the genes that are needed to make every component of our cells and tissues. RNA is essentially the middle-man.  RNA is made by a cell when it wants to turn on a specific gene, or in other words, when a cell requires a specific protein to carry out a specific function. This RNA is then used by the cell to make building blocks which are joined together to make a protein. This process is tightly controlled so that cells in different tissues can switch on and switch off genes depending on the cell’s role. For example, immune cells need to turn on genes which help them kill infected cells, whereas muscle cells need to turn on genes to make muscle fibres that enable the cells to contract. Thus, investigating the levels of RNA within a tissue or cell allows you to understand which genes have been switched on and off. The process of making a protein by translating DNA into RNA is summarised in the image below.

Image made using Biorender.com

In the laboratory, RNA can be measured using RNA sequencing, a technique used to read the genetic code of the RNA. The RNA sequences are then compared with DNA to identify which genes have been turned on. Importantly, we can work out how many copies of the gene has been produced by counting the number of RNA molecules for each gene. We refer to this information as the expression level of each gene.

What were the findings of this research?

The results of the RNA sequencing experiment indicated that the expression levels of 160 genes were increased in AA skin compared to non-AA skin. In this list, genes which are switched on in response to an inflammatory protein released by killer T cells were increased. This protein is called interferon gamma (IFN𝛾). This was what we expected based on what is already known about AA. Next, we investigated the expression of genes associated with other immune cells. We decided to focus on immune cells called macrophages because we know that they respond to IFN𝛾. Macrophages are immune cells which are important during infections but they are also important in healthy tissues. Interestingly, our data indicated that the expression of genes expressed by macrophages changes in AA skin compared to non-AA skin.

What do the results mean?

The RNA sequencing data tells us that macrophages are behaving differently in AA skin because they are changing the expression of specific genes. This is interesting because macrophages have not been studied in AA before. Notably, there are published studies which indicate that macrophages are important for controlling normal hair growth. We think therefore, that the changes in macrophages in AA skin may be affecting hair follicle function. Whilst our data give us clues about the behaviour of the macrophages, they do not yet tell us about what they are doing in AA skin or how they might be interacting with hair follicles. Our next steps are to investigate exactly what the macrophages are doing and to find out whether they contribute to the processes preventing hair regrowth in AA.

Future plans and thank you

I am very happy to share that I have now finished my PhD, which was funded by Medical Research Scotland and AstraZeneca. We had therefore made plans to apply for new funding to continue our research, but these plans were delayed due to the ongoing COVID-19 pandemic. We submitted an application for funding at the end of last year and we are thrilled to share that the application was accepted. This funding will support our research for another 2.5 years, in addition to supporting the costs of the research clinic and biobank. This funding is provided by NHS Scotland, through the Chief Scientist Office.

My PhD, and all of our research to date, wouldn’t have been possible without all of the samples which have been donated. I am very grateful to everyone who has volunteered to take part over the last few years. I would also like to acknowledge the initial funding from Autoimmune Alopecia Research-UK (now Alopecia UK) to set up the research clinic and biobank. Without this, none of my work would have been possible. Thank you to everyone who contributed and fundraised for this - this initial seed was vital to get things started, and for obtaining all the subsequent research funding for this project.

Thanks to Kym for this update. It's exciting to see that the Alopecia Biobank, initially funded by AAR-UK (now Alopecia UK), is leading to exciting findings from Kym's continued work. It is also wonderful news that Kym has received further funding to continue her alopecia areata research for another 2.5 years. We look forward to seeing future breakthroughs and hope these will contribute to new treatments. 

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