Update (November 2022):

The researchers have been investigating the role of a protein called Trichohyalin (TCHH) in hair follicles, the mini-organs in the skin that produce strands of hair. During previous work over the course of 15 years, they identified Trichohyalin as a potential protein of interest in alopecia areata (AA). In the active growth stage of the hair cycle (anagen), Trichohyalin is one of the first proteins that becomes active in the hair follicles. Proteins are structures made up of amino acids ('the building blocks of life'). They can undergo structural changes which affect how they interact with their environment. One of these structural changes is called citrullination, in which the amino acid 'arginine' is transformed into 'citrulline'. The researchers believe this structural change could be one trigger for the immune system to attack its own hair follicles.

So far, they have discovered that these structural modifications to Trichohyalin happen in the bulb region of the hair follicle, located at the bottom. As the hair follicles grow, these modifications gradually increase. They have also used incredibly high magnification microscopes to zoom in on the hair follicle and identified the precise location of Trichohyalin proteins in the hair follicle bulb region. They are now collecting blood samples of people with and without AA. They hope this will allow them to further identify which parts of the Trichohyalin protein are triggering an immune response against hair follicles. They presented their findings at an annual symposium at the UCD Conway Institute and won a commendation prize for the poster presentation. They also published a review article titled: 'Autoantigen Discovery in the Hair Loss Disorder, Alopecia Areata: Implication of Post-Translational Modifications' in the Journal Frontiers in Immunology in June 2022.

Image - Tricohyalin in the hair follicle at different levels of magnification (Trichohyalin location indicated by the red arrows).

Latest update (March 2024): 

The aim of the project was to find out if the protein trichohyalin could potentially be an 'autoantigen' in alopecia areata. This would mean that highly trained immune cells (T cells) mistakenly recognise this protein as dangerous, and start attacking the hair follicle as a result. 

All three objectives (plus an extra one) of the research have now been completed. The first objective was to take images (under a microscope) of trichohyalin proteins, and identify where in the hair follicle they are located. We know from other research that in alopecia areata, high numbers of immune cells infiltrate around the bulb region (lower part) of the hair follicle, so this is a likely area for attack. The researchers showed that the location of Trichohyalin in the bulb region is close to blood vessels which contain immune cells, suggesting that interactions between immune cells and these proteins are possible. 

The second objective was to look at modifications to the trichohyalin proteins in the upper region, above the hair follicle bulb, and compare it to trichohyalin proteins in the bulb region. Because of how the hair follicle grows, the upper region is more 'mature', meaning it has had more time to undergo changes. They found that the Trichohyalin proteins in the upper region had more modifications than those in the lower region. 

Using computer analysis, they then looked at different fragments of the trichohyalin protein, to predict which parts may interact with immune cells. They found that some fragments of the trichohyalin protein have a higher chance of starting an immune response in people with alopecia areata, compared to control subjects.

Finally, they also tested how immune cells in blood from people with alopecia areata react to these fragments of the trichohyalin protein, and their initial findings show an increased reaction to a specific fragment of the trichohyalin protein in blood from people with alopecia areata, compared to controls. 

Together, these very promising results suggest trichohyalin could be a major autoantigen in alopecia areata, but further research is needed to confirm these findings and potentially identify therapeutic strategies to target this mechanism. The researchers are working on a scientific publication of their findings. 

Project information

Alopecia UK funds invested: £18,500 

When:  September 2021 - June 2023

Project type:  Immunology and biochemistry laboratory studies

Project Lead:  Dr Shahnawaz Jadeja

Research Institute: Charles Institute of Dermatology, University College Dublin

Condition of interest:  Alopecia Areata

Funds being used for:  Laboratory chemicals and materials (consumables) and access to equipment and facilities

Research question: 

Does the protein trichohyalin, which is known to undergo chemical modification  in the growing  hair follicle, trigger and/or enhance the autoimmune attack on hair follicles in alopecia areata?

Justification for research project: 

In their previous studies, Professor Desmond Tobin and his team found that patients with alopecia areata had circulating antibodies in their blood that could latch onto a protein called Trichohyalin (TCHH), which is normally found in the growing hair follicle. Because antibodies are normally made when the immune system reacts to destroy something, and alopecia areata is  presumed to be an autoimmune condition, they wondered if this was a sign that TCHH is a target for the autoimmune attack on hair follicles in these patients. This new project funded by Alopecia UK aims to investigate this question more closely. Shahnawaz and Desmond will work with collaborator Dr Dmitri Wall, a dermatologist who runs a specialist hair clinic in Dublin, to invite patients with alopecia areata to donate samples of skin and blood for examination.

TCHH is one of the earliest proteins to form in the hair follicle when it starts to grow new hair, during which TCHH naturally undergoes certain chemical changes known as citrullination and deamidation. The team know already that similar chemical changes to different proteins can provoke immune responses in people who are genetically prone to developing  autoimmune disorders such as rheumatoid arthritis and coeliac disease. They suspect that such chemical alterations to TCHH may make it more ‘visible’ to the immune system and as a result, could provoke an immune attack on hair follicles. The team will look at small segments of TCHH to investigate which parts of the protein, and which particular chemical changes, are recognised not only by patient antibodies but also by the cells of the immune system, and whether there are differences between people with alopecia areata and healthy ‘control’ volunteers. The project also involves getting access to expensive equipment for doing an analytical technique of mass spectrometry, which can detect individual changes in proteins like TCHH.

The team hope that this work will help to pinpoint more precisely what is triggering or aggravating the autoimmune response in alopecia areata. If they succeed, the results could pave a way for the development of a new approach to treating alopecia areata, involving re-training immune cells to ignore the chemical triggers that would otherwise provoke inflammation.

Who is leading the project: 

Dr Shahnawaz Jadeja is a postdoctoral scientist, working in the laboratory of  Professor Desmond Tobin, a researcher specialising in skin science, at the Charles Institute of  Dermatology, University College Dublin. Shahnawaz is originally from India and has previously done research on another autoimmune skin condition, vitiligo. He brings experience of many different techniques to the current study of alopecia areata.