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Diet and Microbiome Influence on Alopecia Areata: Experience from Case Reports

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Alopecia areata (AA) is a potentially reversible auto-immune non-scarring baldness on the scalp, which can be extended to the entire body. There are many scientific evidence as regards the impact of diet on scalp diseases related to hair growth. Diet is also able to strongly influence gut microbiome. On the contrary, few evidence reports as regards the link between microbiome, especially scalp microbiome and hair diseases. Here we reported a two case-reports study on patients affected by AA, with and without lactose intolerance, respectively, with the aim to underline how diet could emphasize microbiome changing related to scalp disease. Subjects were asked to fill out a 7-day dietary survey and scalp and oral swabs were collected. Data from the dietary survey, qRT-PCR on main bacterial strains inhabiting the scalp and 16S sequencing of the scalp and oral microbiome were matched and compared each other and with healthy and general AA population. Beyond diet well-known impact on general human health, our results highlighted the role of diet in modifying oral and scalp microbiome, which in turn seems to have an impact on AA evolution. The findings of the present works suggested a kind of intercorrelation between microbial dysbiosis on the scalp of patients with AA and dietary habits.
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Rinaldi et al. J Nutri Med Diet Care 2019, 5:037
Volume 5 | Issue 1
DOI: 10.23937/2572-3278.1510037
ISSN: 2572-3278
Open Access
Journal of
Nutritional Medicine and Diet Care
Citaon: Rinaldi F, Pinto D, Giuliani G, Sorbellini E (2019) Diet and Microbiome Inuence on Alopecia
Areata: Experience from Case Reports. J Nutri Med Diet Care 5:037. doi.org/10.23937/2572-
3278.1510037
Accepted: July 20, 2019: Published: July 22, 2019
Copyright: © 2019 Rinaldi F, et al. This is an open-access arcle distributed under the terms of the
Creave Commons Aribuon License, which permits unrestricted use, distribuon, and reproducon
in any medium, provided the original author and source are credited.
Page 1 of 8 Rinaldi et al. J Nutri Med Diet Care 2019, 5:037
Diet and Microbiome Inuence on Alopecia Areata: Experience
from Case Reports
Fabio Rinaldi, MD1,2,3*, Daniela Pinto1,2,3, Giammaria Giuliani1,22,3
1Giuliani S.p.A., Italy
2Human Advanced Microbiome Project-HMAP, Italy
3Internaonal Hair Research Foundaon (IHRF), Italy
*Corresponding author: Rinaldi Fabio, MD, Internaonal Hair Research Foundaon (IHRF), Milan, Italy, Tel: +39-2-
76006089
Abstract
Alopecia areata (AA) is a potentially reversible auto-immune
non-scarring baldness on the scalp, which can be extended
to the entire body. There are many scientic evidence as
regards the impact of diet on scalp diseases related to hair
growth. Diet is also able to strongly inuence gut microbi-
ome. On the contrary, few evidence reports as regards the
link between microbiome, especially scalp microbiome and
hair diseases. Here we reported a two case-reports study
on patients affected by AA, with and without lactose intoler-
ance, respectively, with the aim to underline how diet could
emphasize microbiome changing related to scalp disease.
Subjects were asked to ll out a 7-day dietary survey and
scalp and oral swabs were collected. Data from the dietary
survey, qRT-PCR on main bacterial strains inhabiting the
scalp and 16S sequencing of the scalp and oral microbiome
were matched and compared each other and with healthy
and general AA population. Beyond diet well-known impact
on general human health, our results highlighted the role of
diet in modifying oral and scalp microbiome, which in turn
seems to have an impact on AA evolution. The ndings of
the present works suggested a kind of intercorrelation be-
tween microbial dysbiosis on the scalp of patients with AA
and dietary habits.
Keywords
Alopecia areata, Hair disorders, Dietary therapy, Microbi-
ome, Dysbiosis

Check for
updates
nutrient’s intake. Even though the role of macro and
micronutrients in normal hair follicle development has
not been completely claried [2], the impact of diet and
nutrional deciencies on hair growth diseases is well
documented [3,4].
Diet is also reported to have ability of shaping the gut
microbiome [5,6] but also skin microbiome in relaons
to some dermatological condions [7,8] especially acne
and psoriasis. Poor knowledge is currently available as
regards dermatological condions aecng the scalp
and hair growth.
Among hair growth disorders, Alopecia areata (AA)
is reported as the second most common disorder
aecng the scalp [9]. AA is a type of non-scarring
baldness aecng the scalp and, eventually the enre
body [10] which causes have been strictly associated
with immunity and inammaon [9,11,12].
In the past two years researchers focused their at-
tenon also on the role of microbial community inhab-
ing the scalp and hair growth disorders, including AA
[13-17]. More recently Nair and collaborator reported
evidence as regards the role for the gut microbiome
in the pathogenesis of AA [18]. Taking together these
ndings pose the need of a more deeply invesgaon
as regards the link between diet, microbiome and hair
growth disorders.
In the present work, we reported a two case-reports
study on paents aected by Alopecia areata, with and
Introducon
Hair follicle is a dynamic mini-organ [1] with an high
cellular turnover. As a consequence, hair follicle is char-
acterized by a very acve metabolism requiring a good
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Page 2 of 8 Rinaldi et al. J Nutri Med Diet Care 2019, 5:037
me of inclusion. The clinical evaluaon reported 100%
hair loss of the scalp based on the Severity of Alopecia
Tool (SALT) Score [19] with no signs of erythema or
scaling. Eyebrows, eyelashes, and body hair were also
completely absent. The paent demographics include
being Caucasian, weight 72 kg, height 1.80 m, and BMI
22.2 kg/m2.
Case report 2
A 36-year-old female (Figure 3) came to the clinic
reporng a history of strong hair loss since one month.
Other reported symptoms are severe itching, psoriasis
on the scalp, birch and pauliary allergy, insomnia and
high sensaon of fague. The paent is also intolerant
without lactose intolerance, respecvely, with the aim
to underline how diet could emphasize microbiome
changing related to scalp disease (Figure 1).
Case Presentaon
Case report 1
A 17-year-old male (Milan, Italy), aected by Alopecia
universalis (Figure 2). The paent presented to the
dermatology clinic with a history of rapidly progressing
total body hair loss. There was no history of similar
illness in family members and also no history of drug
intake and trauma. Previously treatment includes stem
cell therapy. No therapy for at least 3 months at the
Figure 1: Diet importance in microbiome changing related to scalp disease.
Figure 2: Alopecia universalis affected male.
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Page 3 of 8 Rinaldi et al. J Nutri Med Diet Care 2019, 5:037
to lactose. Clinical evaluaon showed strong hair loss
but no signal of miniaturizaon. Alopecia areata was
conrmed by histological examinaon. No therapy for
at least 3 months at the me of inclusion. The paent
demographics include being Caucasian, weight 48 kg,
height 1.62 m, and BMI 18.3 kg/m2.
Nutrient intake
Both subjects were asked to ll out a 7-day dietary
survey at the me of enrollment, following being
instructed by a diecian on how to record the food and
beverages consumed. The Winfood soware (Winfood
2.7 Medimaca Srl, Colonnella, Italy) was used for
analysis of surveys by esmang the energy intake and
the percentage of macronutrients and micronutrients.
Data collected were compared to the tables of food
consumpon and recommended dietary intakes of
the Italian Naonal Instute of Nutrion and Food
Composion Database in Italy.
Samples collecon
Before sampling paents had to avoid the use of
anbiocs in the last 30 days no probiocs, the use
of probiocs in the last 15 days, to perform the last
shampoo 48 h before sampling. They also did not have
to undergo to an-tumor, immunosuppressant or
radiaon therapy in the last 3 months and also topical
or hormonal therapy on the scalp. The study was under
the approval of the Ethical Independent Commiee for
Clinical, not pharmacological invesgaon in Genoa
(Italy) and in accordance with the ethical standards of
the 1964 Declaraon of Helsinki. All of the volunteers
signed the informed consent.
Microbiome samples were collected from the scalp
(minimum area sampled of 16 cm2) and oral mucosa with
a sterile coon swab, previously soaked in ST soluon
(NaCl 0.15 M and 0.1% Tween 20) for at least 30s
[20,21]. Samples from the same subjects were collected
together and stored at 4°C unl DNA extracon. Sterile
coon swabs placed in ST soluon have been used as
negave controls.
DNA extracon and 16s amplicon generaon and
sequencing: Genomic DNA from scalp swabs was ex-
tracted by mean of QIAamp UCP Pathogen Mini Kit
(Qiagen) according to manufacturer protocol, with mi-
nor modicaons [22]. Aer extracon, bacterial DNA
was suspended in DNAse free water and quaned by
the QIAexpert system (Qiagen) before sequencing and
qRT-PCR.
For sequencing, variable region V3-V4 was ampli-
ed by mean of the following universal primers: 341 F
CTGNCAGCMGCCGCGGTAA [23,24] and 806bR GGAC-
TACNVGGGTWTCTAAT [25-27]. Library preparaon and
Illumina MiSeq V3-V4 sequencing were carried out at
StarSEQ GmbH, Mainz, Germany, according to Capora-
so, et al. [28] and Kozich, et al. [29] methods, with mi-
nor modicaons. Real-Time Analysis soware (RTA) v.
1.16.18 and 1.17.22, MiSeq Control Soware (MCS) v.
2.0.5 and 2.1.13 were using.
qRT-PCR of main bacterial species: Main bacterial
species (Propionibacterium acnes, Staphylococcus epi-
dermidis and Staphylococcus aureus) on the scalp were
quaned by real-me quantave PCR (RT qPCR),
using Microbial PCR assay kit (Qiagen). Samples were
mixed with 12.5 μL of Microbial qPCR Mastermix, 1 μL
of Microbial DNA qPCR Assay, 5 ng of genomic DNA
sample and Microbial-DNA-free water up to a nal
volume of 25 μL. Posive PCR Control, No Template
Control, and Microbial DNA Posive Control were also
included. Pan-bacteria assays are also included as pos-
ive controls for the presence of bacterial DNA, as hu-
man GAPDH and HBB1 for the determinaon of proper
sample collecon. Following thermal cycling condions
were used: 95 °C for 10 min, 40 cycles of 95 °С for 15
sec, 60 °C for 2 min. Each PCR reacon was performed in
duplicate using an MX3000p PCR machine (Stratagene,
La Jolla, CA). Relave abundance in the expression of
each strain was calculated using the ΔΔCt method [30],
normalizing fold-change against Pan Bacteria, using
MX3000p soware (v.3; Stratagene).
Stascal analysis
Data are expressed as Relave abundance % ± SEM
for qRT-PCR analysis. Results were checked for normal
distribuon using the D'Agosno & Pearson normality
test before further analyses. Stascally signicant
dierences in the bacterial community were determined
by Student's t with Welch's correcon. Analyses
were performed with GraphPad Prism 7.0 (GraphPad
Soware, Inc., San Diego, CA). P-values equal to or less
than 0.05 were considered signicant.
Results and Discussion
In the present work, we invesgated diet impact
on microbial dysbiosis caused by the presence of AA
which in turn could impact on disorder evoluon and
manifestaons.
The preliminary analysis of macronutrients % in-
take (data not shown) suggested a Mediterranean diet
framework [31] for both case reports included in the
present study. Case report 1 diet included processed
food, red meat and low intake of fruits and vegetables.
Case report 2 diet included vegetables, fruit, peas, and
beans (legumes) and grains. When analyzed more deep-
ly as regards the type of proteins, lipids and carbohy-
drates ingested, diet from case-report 1 is beer classi-
ed as High fat-diet (more processed food, sugars, and
few bers). The second case reports can be considered,
instead, as following the Mediterranean like diet (lower
fruits intake compared to normal Mediterranean regi-
men).
Tables 1 and Table 2 show the intake of macronutri-
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Page 4 of 8 Rinaldi et al. J Nutri Med Diet Care 2019, 5:037
The daily amount of total calories was signicantly
dierent among case reports (p < 0.01) (1,331.58 ±
ents and micronutrients in both case reports, compared
to Recommended (LARN) values in Italy.
Table 1: Daily reported energy and nutrient intake of studied case reports, assessed by a 7-day weighed food record. LARN:
Nutrition and Energy Reference Assuming Levels. a-cValues with different superscript letters, in the same row, differ signicantly
(P < 0.05).
Daily Intake Recommended
(LARN)
Case report 1 Case report 2
Total calories
(kcal/day)
M: 2000-2400a
F: 1800-2300
1,331.58 ± 189.61b693.09 ± 143.48c
Total proteins
(g/day)
75a60.93 ± 15.19a37.11 ± 16.01b
Animal proteins
(% of total proteins)
40a72.44 ± 10.14b47.33 ± 2.01a
Vegetal proteins
(% of total proteins)
60a27.56 ± 11.22b52.67 ± 4.05a
Total lipids
(g/day)
65a50.58 ± 18.81a29.11 ± 4.64b
Total carbohydrates
(g/day)
290a165.80 ± 22.15b75.54 ± 18.88c
Amide
(g/day)
220a95.15 ± 35.35b27.72 ± 28.77b
Fiber
(g/day)
23a16.59 ± 13.23a7.44 ± 1.33b
Cholesterol
(mg/day)
255a126.50 ± 81.79a51.76 ± 39.61b
Saturated fatty acids
(% of total)
7a10.06 ± 6.31a3.12 ± 1.00b
Polyunsaturated fatty acids
(% of total)
18a6.45 ± 1.31b6.36 ± 1.82b
Monounsaturated fatty acids
(% of total)
4a11.74 ± 5.01b15.06 ± 5.24b
Table 2: Daily reported micronutrient intake of studied case reports, assessed by a 7-day weighed food record. LARN: Nutrition
and Energy Reference Assuming Levels. a-cValues with different superscript letters, in the same row, differ signicantly (P < 0.05).
Daily Intake Recommended
(LARN)
Case report 1 Case report 2
Calcium (mg) M: 1200a
F: 1500
419.06 ± 406.77b141.05 ± 47.31c
Iron (mg) 18a5.50 ± 1.66b4.26 ± 1.91b
Zinc (mg) 7a7.33 ± 2.59a4.03 ± 1.30a
Folic acid (µg) 200a149.25 ± 43.89a67.33 ± 24.08b
Niacin (mg) 14a7.79 ± 3.45b9.05 ± 4.22b
Riboavin (mg) 1.2a0.45 ± 0.11b0.46 ± 0.25b
Thiamine (mg) 0.9a0.65 ± 0.16a0.48 ± 0.30a
Vitamin A (µg) 600a1,147.00 ± 141.88b499.68 ± 351.71c
Vitamin B6 (mg) 1.1a0.99 ± 0.38a0.70 ± 0.29a
Vitamin C (mg) 70a42.33 ± 25.41a19.57 ± 29.15a
Vitamin D (µg) 10a0.78 ± 1.48b4.58 ± 6.55a
Vitamin E (mg) 8a3.21 ± 2.57b10.25 ± 3.81b
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Page 5 of 8 Rinaldi et al. J Nutri Med Diet Care 2019, 5:037
report 1 and case report 2, respecvely. Case report 1
also has a signicant (p < 0.01) lower intake of niacin
(7.79 ± 3.45) and vitamin E (3.21 ± 2.57) and higher (p <
0.001) intake of vitamin A.
Unbalancing in nutrients intakes is reported to have
an inuence both on hair follicle structure and hair
growth diseases such as telogen euvium, androgenet-
ic alopecia, AA and cicatricial alopecia [4,32-35].
Indeed, many of the above cited micronutrients are
reported to aect the hair follicle as regards restoraon
of hair growth, cell division, cycling [3]. Therefore, Singh
and collaborators [5] also highlighted diet eect on gut
microbiome. The same eect has been reported on oral
microbiome [36].
189.61 and 3.09 ± 143.48, respecvely) (Table 1).
Food diary from both subjects also reported a very
small intake of ber (16.59 ± 13.23 and 7.44 ± 1.33,
respecvely) and polyunsaturated fay acids (6.45 ±
1.31 and 6.36 ± 1.82, respecvely). Therefore, a lower
percentage of saturated fay acid intake was reported
for case report 2 (3.12 ± 1.00).
As regards micronutrients intake (Table 2) we
noced signicant lower intake of iron (5.50 ± 1.66 and
4.26 ± 1.91 vs. recommended) (p < 0.001) and folic acid
(149.25 ± 43.89 and 67.33 ± 24.08 vs. recommended)
(p < 0.01), riboavin (0.45 ± 0.11 and 0.46 ± 0.25 vs.
recommended) (p < 0.01) and vitamin D (0.78 ± 1.48
and 4.58 ± 6.55 vs. recommended) (p < 0.01) for case
Figure 4: Distribution of main bacterial strains in healthy subjects and AA subjects.
Figure 3: Women with initial stages of Alopecia areata.
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Page 6 of 8 Rinaldi et al. J Nutri Med Diet Care 2019, 5:037
sults found in another autoimmune disease [42]. In both
case reports, an increase of Proteobacteria (33.28% and
27.71%, respecvely) has been reported. Most interest-
ing, analysis of sequences from case report 1 bacterial
oral DNA showed a decrease in Bidobacteria. A link
between a high-fat diet and this phylum decrease was
previously reported [43] thus conrming the role of diet
in inuencing oral bacterial composion. A signicant
reducon of Bacteroidetes has been found in case re-
port 2 compared to healthy control subjects. Since the
high intake of n-6 PUFA by case report 2, a link between
diet and this microbial unbalance could be hypothesized
as also suggested by some authors [44].
Results on bacterial composion of scalp microbi-
ome conrm our previous ndings on microbial shi
on the scalp in paents aected by AA [14,15]. In the
present work, we invesgated if dierent dietary habits
can re-modulate this microbial dysbiosis with the aim
to highlight the strict intercorrelaon between diet and
oral but especially scalp microbiome of these subjects.
The case reports of the present work represent just an
example of a larger clinical invesgaon we are leading
on this topic. For example, our clinical observaons sug-
gest that, in some paents aected by non-celiac gluten
sensivity (NCGS), AA manifestaons systemacally re-
curred following a non-gluten free diet. An explicave
photographic example was reported in Figure 6. Most
interesng this modulaon reects also in the microbi-
al composion of scalp microbiome (data not shown)
enhancing the existence of a link between diet and skin
bacterial communies scalp microbiome.
Data from the present study add to knowledge to
this evidence also highlighng that not only gut but
Evidence on the inuence of diet and microbiome
dysbiosis on skin disorders are mainly linked to topic
dermas [37], acne vulgaris [8,38-40], and psoriasis
[41]. In our previous works [14,15] on scalp microbial
community in hair growth disorders we showed, for the
very rst me, the presence of scalp bacterial shi in
such kind of disorders.
Figure 4 reports the % of the distribuon of main
bacterial strains in case report 1 and case report 2
compared with data from 15 healthy subjects and 15 AA
subjects in our database.
Data from case report 1 showed an increase in
P. acnes populaon and parallel decrease both of S.
epidermidis and S. aureus species. These data are in
line with data from the panel of AA subjects and clearly
evidence the presence of bacterial dysbiosis compared
to healthy control.
On the contrary, the percentage of distribuon of
main bacterial species in case report 2 resulted more
similar to the healthy populaon (Figure 4). Even if an
interindividual dierence has to be considered, the
analysis of food diary of the panel of een AA subjects
and case report 1 and 2 strongly suggested the impact
of diet in shaping scalp microbiome.
Data from oral bacterial DNA sequencing corrobo-
rated these ndings (Figure 5). Also, in this case, data
from case report 1 and 2 were compared to data from
our internal database of healthy and AA subjects, previ-
ously collected. The analysis of sequence at the phylum
level highlighted a slow decrease of Firmicutes both for
case report 1 and 1 (Figure 6) and these results are in
line with our previous ndings in AA subjects and re-
Figure 5: Data from oral bacterial DNA sequencing corroborated these ndings.
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Page 7 of 8 Rinaldi et al. J Nutri Med Diet Care 2019, 5:037
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18. L Nair, Z Dai, AM Christiano (2017) 649 Gut microbiota
also oral and scalp microbiome could be modulated by
dietary habits.
Nowadays, the study of human microbiome rep-
resents a novel diagnosc and therapeuc approach to
treat many human condions, also including that strict-
ly related to skin and scalp. Beyond diet well-known im-
pact on general human health, our results highlighted
the role of diet in modifying oral and scalp microbiome,
which in turn seems to have an impact on Alopecia
areata evoluon.
According to our ndings and previous reported
evidence cited above, the modulaon of the gut
microbiome by mean of diet could represents a valid
approach in the managing of hair growth disorders,
especially AA, in which also the permeability of the gut
can be compromised [44].
Acknowledgment
This study was supported by Giuliani SpA.
Conict of Interest
R.F. and S.E. serve as a consultant for Giuliani S.p.A.
P.D. is employed by Giuliani S.p.A.
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Figure 6: A slow decrease of Firmicutes.
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... The role of diet in AA can also be hypothesised [101,102]. Firstly, an unbalanced diet can lead to a lower intake of some macronutrients and micronutrients, and this can have an impact on gut microbial composition and functionality as well as the microbiome inhabiting the scalp up to the perifollicular region [101]. Hair is a fast-growing element, which needs a balanced supply of nutrients to grow correctly [9,102]. ...
... Firstly, an unbalanced diet can lead to a lower intake of some macronutrients and micronutrients, and this can have an impact on gut microbial composition and functionality as well as the microbiome inhabiting the scalp up to the perifollicular region [101]. Hair is a fast-growing element, which needs a balanced supply of nutrients to grow correctly [9,102]. ...
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The continuous research advances in the microbiome field is changing clinicians’ points of view about the involvement of the microbiome in human health and disease, including autoimmune diseases such as alopecia areata (AA). Both gut and cutaneous dysbiosis have been considered to play roles in alopecia areata. A new approach is currently possible owing also to the use of omic techniques for studying the role of the microbiome in the disease by the deep understanding of microorganisms involved in the dysbiosis as well as of the pathways involved. These findings suggest the possibility to adopt a topical approach using either cosmetics or medical devices, to modulate or control, for example, the growth of overexpressed species using specific bacteriocins or postbiotics or with pH control. This will favour at the same time the growth of beneficial bacteria which, in turn, can impact positively both the structure of the scalp ecosystem on the host’s response to internal and external offenders. This approach, together with a “systemic” one, via oral supplementation, diet, or faecal transplantation, makes a reliable translation of microbiome research in clinical practice and should be taken into consideration every time alopecia areata is considered by a clinician.
... TCHH is also subjected to transglutaminase-mediated deamidation, which suggests similarities with other deamidation-mediated autoimmune disorders (e.g., celiac disease). Moreover, several reports have suggested comorbidity of celiac disease in AA patients (119)(120)(121), and some have speculated that an underlying intestinal inflammation may prime patients predisposed to AA (46). ...
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Alopecia areata (AA) is a chronic, multifactorial, polygenic, and heterogeneous disorder affecting growing hair follicles in susceptible individuals, which results in a non-scarring and reversible hair loss with a highly unpredictable course. Despite very considerable research effort, the nature of the precipitating factor(s) responsible for initiating AA in any given hair follicle remains unclear, due largely to significant gaps in our knowledge of the precise sequence of the etiopathogenic events in this dermatosis. However, disease-related changes in the immune-competence of the lower growing hair follicle, together with an active immune response (humoral and cellular) to hair follicle-associated antigens, are key associated phenomena. Confirmation of the hair follicle antigen(s) implicated in AA disease onset has remained stubbornly elusive. While it may be considered somewhat philosophical by some, it is also unclear whether immune-mediated hair loss in AA results from a) an ectopic (i.e., in an abnormal location) immune response to native (unmodified) self-antigens expressed by the healthy hair follicle, b) a normal immune response against modified self-antigens (or neoantigens), or c) a normal immune response against self-antigens (modified/non-modified) that were not previously visible to the immune system (because they were conformationally-hidden or sequestered) but become exposed and presentable in an MHC-I/-II molecule-restricted manner. While some candidate hair follicle antigen target(s) in AA are beginning to emerge, with a potential role for trichohyalin, it is not yet clear whether this represents the initial and immunodominant antigenic focus in AA or is simply one of an expanding repertoire of exposed hair follicle tissue damage-associated antigens that are secondary to the disease. Confirmation of autoantigen identity is essential for our understanding of AA etiopathogenesis, and consequently for developing a more informed therapeutic strategy. Major strides have been made in autoantigen discovery in other autoimmune conditions. In particular, some of these conditions may provide insights into how post-translational modifications (e.g., citrullination, deamidation, etc.) of hair follicle-restricted proteins may increase their antigenicity and so help drive the anti-hair follicle immune attack in AA.
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