Making Sense of Molecules I am a 3rd year PhD student at Glasgow University. My project focuses on identifying how the immune system drives hair loss. I use blood, skin and stool samples collected at the Alopecia Areata Research Clinic in Glasgow and held in the Alopecia Biobank. Along with Simon Milling (my PhD supervisor) and other colleagues, we recently published a paper in the British Journal of Dermatology that describes molecules increased in the blood of people with Alopecia Areata, and how they may be associated with the psychological impact of the disease.What were the main findings of our study? In our paper, we have shown that people with Alopecia Areata have increased levels of specific kinds of molecules in their blood. These molecules are produced by immune system cells when they are activated. Our immune system normally produces these molecules in response to infections to allow us to fight bacteria and viruses. We found that 11 different molecules, produced by the immune system, are found at high levels in blood from people with Alopecia Areata. The different molecules provide clues to what sort of immune responses are turned on in someone who has hair loss. We can split these 11 molecules into 2 different groups. The first group of molecules is increased in people with other diseases caused by the immune system, such as psoriatic arthritis (a disease that has joint and skin symptoms). The second group of molecules have been associated with other diseases that are caused by allergic responses, such as dermatitis.The second part of the paper focuses on the psychological aspects of Alopecia Areata. It’s well known that many people with this condition (about 60%) will develop depression and/or anxiety which can be very detrimental to everyday life. When we got the results described above, we wanted to know if these molecules could be contributing to how some people feel when they have alopecia. This is because scientists have shown that in other diseases caused by the immune system, such as rheumatoid arthritis, depression and anxiety are affected by these molecules. To look into this, we used complex equations, and found that two specific molecules that are increased in people with AA are associated with a how depressed a patient is.How did we do this study? This study used blood samples from 39 people with a diagnosis of Alopecia Areata. Each sample was collected from a volunteer at the Glasgow research clinic and brought back to the University. In the lab, we separated the plasma (cloudy portion of blood that contains the molecules described above) from the red and white blood cells. We then measure amounts of molecules using a test that takes a few hours. It works by labelling specific molecules in the sample with a fluorescent-coloured tag. We then use a machine that measures the different colours from each sample and calculates how much of a specific molecule is present. We did the exact same test in blood samples from people without Alopecia Areata, so we have measurements for comparison. By comparing the levels in the alopecia group and other group, we found that 11 molecules were increased in samples from people with Alopecia Areata.The other part of this study, focussing on the psychological aspects of Alopecia Areata, was possible because all of our study participants complete a questionnaire at the clinic called the Hospital Anxiety and Depression Score (HADS). These 10 questions that assess your mental health can be used to generate separate anxiety and depression scores.What does this study actually mean for people with alopecia areata? This study tells us what type of immune cells are activated in Alopecia Areata, with more detail than previous studies. Other studies have shown similar findings in other groups of patients, so we can be sure that these molecules are associated with having hair loss caused by Alopecia Areata. The findings are interesting because they highlight similarities with other diseases. Identifying parallels between different diseases is useful because it helps to understand what causes Alopecia Areata, and to potentially investigate how we can use drugs used to treat other diseases to promote hair regrowth. The link with depression is also important. At this stage, we don’t know that these molecules are directly causing changes in the brain that cause depression. However, other scientists have found that immune molecules can change the levels of chemicals in the brain involved in psychological symptoms. We and others think that this information is important for people who suffer from autoimmune diseases, because it shows that the immune response causing hair loss may also be contributing to the anxiety and depression that people with alopecia often experience. For Alopecia Areata, more research is now needed to understand the links between the immune response that damages hair follicles, and the effects of the condition on the brain.Our paper was published in the British Journal of Dermatology. Full reference: Bain KA, McDonald E, Moffat F, Tutino M, Castelino M, Barton A, Cavanagh J, Ijaz UZ, Siebert S, McInnes IB, Astrand A, Holmes S, Milling SWF. (2019) Alopecia areata is characterised by dysregulation in systemic type 17 and type 2 cytokines, which may contribute to disease-associated psychological morbidity. British Association of DermatologyMy study is supported by samples from the Alopecia Biobank funded by Alopecia UK. 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