Original article 21
Serum activin-A as a predictive marker for postacne scarring
Ahmed Abdel-Barya, Eman Tayaeb, Basma Magdya, Tarek Husseina
Departments of aDermatology, Venereology
and Andrology, bClinical Pathology, Faculty of
Medicine, Alexandria University, Alexandria,
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Egypt
Correspondence to Ahmed Abdel-Bary, MD,
22 Ishak Street, Shods, Al-Raml, Alexandria,
Egypt Tel: +20 128 284 0574;
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e-mail: drahmedabdelbary2016@gmail.com
Received: 24 June 2022
Revised: 26 July 2022
Accepted: 1 August 2022
Published: 31 October 2022
Journal of the Egyptian Women's
Dermatologic Society 2023, 20:21–25
Introduction
Acne is a common inflammatory disease of the
sebaceous glands affecting mainly teenagers [1].
Increased production of sebum, changes of sebum
lipid quality, altered follicular keratinization,
proliferation of Propionibacterium acnes within the
sebaceous glands, and inflammation are the main
pathogenic factors [2]. Postacne scar is the most
distressing complication of inflammatory acne
vulgaris, which affects the self-esteem and social
relations of the patients [3]. Postacne scar develops
due to abnormal wound healing process in response to
inflammation [4]. Decreased deposition of collagen
results in the formation of atrophic scars; however, if
the healing response is exaggerated, hypertrophic scars
develop [5]. Activins are members of the transforming
growth factor (TGF-b) family. It was found that
activins are involved in angiogenesis, inflammation,
immunity, and wound healing [6]. On the contrary,
it may induce fibrosis and scar formation in lung
fibrosis, liver cirrhosis, and arteriosclerosis [7]. Oral
© 2022 Journal of the Egyptian Women's Dermatologic Society | Published by Wolters Kluwer - Medknow
Background
Postacne scar is the most distressing sequelae of inflammatory acne vulgaris. It
develops owing to abnormal wound healing process in response to inflammation.
Activins are members of the family named transforming growth factors-b that are
involved in inflammation, immunity, and wound healing.
Objective
To evaluate human activin-A as a predictive marker for postacne scarring and the
effect of treatment with oral isotretinoin on its serum level.
Patients and methods
A total of 40 patients who presented with either moderate or severe acne vulgaris
were selected for this case–control study. Patients were classified into two groups:
group A had no scarring and group B had postacne scarring. Group B patients were
treated with oral isotretinoin therapy. Measurement of serum activin-A levels was
done using the enzyme-linked immunosorbent assay technique.
Results
The mean serum level of human activin-A was significantly higher in patients
with postacne scarring (189.47±59.63 ng/ml) than patients without scarring (155.4
±41.19 ng/ml). Moreover, the mean serum level of human activin-A in group B was
significantly decreased after treatment with oral isotretinoin. Patients with serum
human activin-A level of more than 144.8 ng/ml are more liable to develop postacne
scarring with 80.0% sensitivity and 55% specificity.
Conclusion
Serum level of activin-A could be a good and reliable marker for the prediction of
those patients liable to develop postacne scarring, but more in-depth studies are
still required to detect the exact pathogenic action of activin-A in the development of
acne scars and to test the targeting of activin-A in an attempt to prevent postacne
scarring.
Keywords:
acne, activin, isotretinoin, scar
J Egypt Women’s Dermatol Soc 20:21–25
© 2022 Egyptian Women’s Dermatologic Society | Published by Wolters Kluwer - Medknow
1687-1537
isotretinoin is the most effective drug available for the
treatment of acne, but it has different undesirable side
effects, and its use is more recommended for those
patients prone to develop postacne scar [8]. So, we
aimed to evaluate human activin-A as a predictive
marker for postacne scarring and the effect of
treatment with oral isotretinoin on its serum level.
Patients and methods
The study included 40 patients presented with
moderate to severe acne vulgaris (according to global
acne grading system) [9], who did not receive therapy
for at least 1 month either systemically or topically
before the study. Patients were selected from the
Dermatology Outpatient Clinic and Dermatology &
This is an open access journal, and articles are distributed under the terms
of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
License, which allows others to remix, tweak, and build upon the work
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DOI: 10.4103/jewd.jewd_32_22
 22 Journal of the Egyptian Women's Dermatologic Society, Vol. 20 No. 1, January-April 2023
Venereology Department of Main University Hospital
of Alexandria, Egypt. Moreover, 20 healthy individuals
(matching for age and sex) were included as a control
groups.
Concomitant skin/systemic inflammatory or
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autoimmune diseases, hepatic and renal insufficiency,
hyperlipidemia, pregnancy, and lactation were the
exclusion criteria.
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All participants assigned informed consents and the
local ethics committee of Alexandria Faculty of
Medicine approved the study (the approval number
was 0106620, and the date of approval was 19-11-
2020).
Patients were divided into two groups:
(1) Group A: 20 cases with moderate/severe acne
vulgaris without scarring.
(2) Group B: 20 cases with moderate/severe acne
vulgaris and postacne scarring.
(a) Group B patients with postacne scarring were
graded using the Qualitative Scarring Grading
System [10]. Patients with mild atrophic or
hypertrophic scarring that is not obvious at
more than or equal to 50 cm distance and
easily masked by makeup were classified as
mild scarring. However, patients with
moderate atrophic or hypertrophic scarring
that is obvious at more than or equal to 50
distance and not easily masked by makeup and
could be flattened manually by skin stretching
were classified as moderate scarring. Finally,
patients with severe atrophic or hypertrophic
scarring that is obvious at more than or equal
to 50 cm distance and not easily masked by
makeup and could not be flattened manually
by skin stretching were classified as severe
scarring.
(b) Group B patients were treated with oral
isotretinoin therapy (0.5 mg/kg body weight
daily for 3 months) and followed up monthly
during the treatment period by complete blood
picture, hepatic and renal function tests, and
serum lipid profile.
Measurement of serum human activin-A levels
Serum human activin-A levels were measured for
patients (groups A and B) and controls using
enzyme-linked immunosorbent assay technique. Re-
estimation of serum human activin-A levels in group B
patients was done after oral administration of
isotretinoin for a period of 3 months.
Overall, 3 ml of venous blood was collected into plain
glass tubes. The tubes were allowed to coagulate at
room temperature and centrifuged immediately at
1000g for l0 min to remove the serum. The serum
samples were separated and kept at −20°C until use.
The serum activin-A levels were measured by an
enzyme-linked immunosorbent assay kit (catalog
number: BEK1002) provided by Chongqing Biospes,
Jiulongpo District, Chongqing, China.
The sandwich enzyme-linked immune-sorbent assay
technique was employed. Anti-activin-A antibody was
first used for precoating of the 96 wells in the used
plate, whereas the detection antibodies were biotin
conjugated (both were polyclonal). Patients’ samples
and biotin-conjugated detection antibody were added
to the wells subsequently. Avidin–biotin–peroxidase
complex was then added. A buffer wash was done after
each step to get rid of the unconjugate. HRP enzyme-
mediated reaction was visualized by TMB substrates.
HRP catalyzes TMB to produce a blue color product.
Then, an acidic stop solution was applied that gave a
yellow color. The density of the latter is proportionate to
the concentration of activin-A in the different samples
within the plates. Then, an acidic stop solution was used
for finalization of the reaction. Then, the absorbance was
calculated at 450 nm. Finally, serum activin-A
concentration in each sample was evaluated by
comparing its OD to the standard curve.
Statistical analysis
The software package IBM SPSS, version 20.0, was
employed (IBM Corp., Armonk, New York, USA).
Qualitative figures were expressed in terms of number
and percentage, whereas quantitative data were
expressed in terms of range (minimum and
maximum), mean, SD, median, and interquartile
range. Testing the normality of distribution of the
used data was done using Shapiro–Wilk test. Level
of significance was judged at 5%.
χ 2 test was employed to compare categorical data,
whereas paired t test was employed for quantitative
data. Comparison between two periods was done using
Student t test for normally distributed data and
Mann–Whitney test for abnormally distributed ones.
On the contrary, comparison between the two groups
was done using Spearman coefficient test for
abnormally distributed data and Pearson coefficient
test between normally distributed data. P value
< 0.05 is considered statistically significant.
Receiver operating characteristic curve (ROC) was
made, where sensitivity was plotted at the Y-axis,
 Serum activin-A and postacne scarring Abdel-Bary et al. 23

whereas 1-specificity was plotted on the X-axis at
variable cutoff values. Area below the curve
indicates the diagnostic performance. Acceptable
performance is more than 50, whereas 100% is the
best performance.
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Serum human activin-A level
The mean serum level of human activin-A was
significantly higher in group B patients with
postacne scarring (189.47±59.63 ng/ml) than group
A patients without scarring (155.4±41.19 ng/ml).
Moreover, its level was significantly higher in both

groups than control (110±25.07 ng/ml) (Table 2).

Results
In the studied group, patients’ age ranged between 17 The mean serum level of human activin-A in group B
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and 30 years (mean=21.10±3.57), whereas in the
studied group, patients’ age ranged between 19 and
24 years (mean=21.35±1.60). This difference was not
significant (P=0.248). Group A included seven (35%)
males and 13 (65%) females. Similar sex distribution
was found in group B. Table 1 shows the distribution of
the cases included in the study according to age, sex,
and duration of the disease.
Grading of group B patients with postacne scaring was
done, where seven (35%) patients had mild scarring, six
(30%) patients had moderate scarring, and seven (35%)
patients had severe scarring.
significantly decreased after treatment with oral
isotretinoin (122.8±27.43 ng/ml) (P≤0.001, paired t
test) (Table 2).
Relation between serum human activin-A level and
other parameters among the studied cases
No significant difference was found in the serum
human activin-A level between males and females in
both groups A and B (P=0.074 and 0.478,
respectively). Moreover, no significant correlation
was detected between serum human activin-A level
and each of age of patients (group A: r=0.409,
P=0.074, and group B: r=0.168, P=0.478) and

Table 1 The distribution of the studied cases according to age, sex, and duration of the disease
Group A (acne vulgaris without Group B (Acne vulgaris with Control group Test of P
scarring) (N=20) [n (%)] scarring) (N=20) [n (%)] (N=20) [n (%)] significance
Sex
Male 7 (35.0) 7 (35.0) 9 (45.0) χ 2=0.564 0.754
Female 13 (65.0) 13 (65.0) 11 (55.0)
Age (years)
Range 17.0–30.0 19.0–24.0 17.0–28.0
Mean±SD 21.10±3.57 21.35±1.60 22.60±3.44 F=1.429 0.248
Median (IQR) 20.0 (18.5–23.0) 21.0 (20.0–22.0) 22.0 (20.0–25.5)
Duration of disease (years)
Minimum–maximum 1.0–4.0 1.0–4.0
Mean±SD 2.30±0.98 2.80±1.01 U=146.0 0.149
Median (IQR) 2.0 (1.50–3.0) 3.0 (2.0–4.0)
χ 2, χ 2 test; F, one-way analysis of variance test; IQR, interquartile range; U, Mann–Whitney test.

Table 2 Comparison between patients and control according to human activin-A serum level (ng/ml)
Group B (acne vulgaris with scarring) (N=20)
Group A (Acne Before treatment After treatment Control group F (P) P
vulgaris without (N=20)
scarring) (N=20)
Activin-A level (ng/ml)
Range 90.14–274.0 131.3–335.2 69.14–170.9 61.36–166.1
∗
Mean±SD 155.4±41.19 189.7±59.63 122±27.43 110.6±25.07 F=16.082 P1=0.045 ,
∗ ∗
P<0.001 P2=0.006 ,
∗
P3<0.001
Median (IQR) 144.4 (133.1–175.3) 164.1 (148.8–217.8) 124.4 (99.9–141.7) 111.9 (99.47–124.4)
t 6.217
∗
P0 <0.001
IQR, Interquartile range; t, paired t test. F, F for one-way analysis of variance test, pairwise comparison between each two groups was
done using post-hoc test (Tukey). P0: P value for comparing group B before and after treatment. P1: P value for comparing between group
A and group B. P2: P value for comparing between group A and control group. P3: P value for comparing between group B before
treatment and control group. ∗P value < 0.05 is considered statistically significant.
 24 Journal of the Egyptian Women's Dermatologic Society, Vol. 20 No. 1, January-April 2023

Table 3 Relation between human activin-A serum level (ng/ml) and grading of acne scarring in group B patients (N=20)
Activin level (ng/ml) in group B (acne vulgaris
with scarring)
N Median (IQR) Mean±SD F P
Grading of scarring
Mild 7 139.8 (131.3–153.9) 142.4±9.64
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∗
Moderate 6 164.1 (146.1–199.5) 170.0±20.42 19.320 <0.001
Severe 7 229.0 (207.5–335.2) 254.0±54.77
F, F for one-way analysis of variance test. ∗P value less than 0.05 is considered statistically significant.
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duration of the disease (group A: r=0.069, P=0.772, Figure 1

and group B: r=0.341, P=0.142) in both groups.

In group B patients with postacne scarring, the mean

serum human activin-A level was significantly higher
in patients with severe scarring (254.0±54.77 ng/ml)
than those with moderate and mild scarring (170.0
±20.42 and 142.4±9.64 ng/ml, respectively) (Table 3).

Receiver operating characteristic curve was done to

detect the cutoff value to discriminate between those
patients liable to develop postacne scarring and others
not liable. Patients with serum human activin-A level
of more than 144.8 ng/ml are more liable to develop
postacne scarring with 80.0% sensitivity and 55%
specificity and overall accuracy of 69.5% (Fig. 1).

Discussion
Acne scarring can affect any patient with acne,
regardless of severity, and represents a great
psychological burden on their lives [11]. Thus, early
recognition of those liable to develop postacne scarring
is strongly needed.
Activin-A, one of TGF-b family, is a final step in the
pathway to fibrosis. It is stimulated by many factors
such as TGF-b1, tumor necrosis factor-α, endothelin,
and interleukin-13 [12]. TGF-b stimulates
myofibroblasts to produce activin-A, and activin-A
can stimulate the production of TGF-b by
fibroblasts [13].
In this study, serum level of activin-A in patients who
developed postacne scarring patients was significantly
higher in comparison with patients without scarring
and healthy control, which sheds light on its role in
the pathogenesis of postacne scarring. In agreement
with our results, Moon et al. [14] found that TGF-b1
was elevated in patients prone to develop acne
scarring. Moreover, Mukhopadhyay et al. [15]
found increased expression of activin in keloids and
hypertrophic scars. So, activin-A could be a good
ROC curve to discriminate between scarring and non-scarring acne
vulgaris using human activin-A serum level. ROC, receiver operating
characteristic.
therapeutic target for the prevention of scarring in
patients with acne.
The exact pathogenic role of activin-A in inducing
scarring is not completely understood, but it had been
found that activin-A stimulates the production of
profibrotic factors, such as tumor necrosis factor-α,
endothelin, and tissue inhibitor of metalloproteinase-1
[16]. Moreover, activin signaling can promote the change
of fibroblasts from normal state to scar forming [17].
In this study, serum level of activin-A significantly
declined after treatment with isotretinoin in patients
with acne vulgaris. This is in accordance with
Shigematsu and Tajima [18], who concluded that
isotretinoin may have antifibrotic effects, and
Haxsen et al. [19], who showed that retinoids
decrease TGF-b gene expression in smooth muscle
fibers of the blood vessels. To the best of our
knowledge, this is the first study to evaluate the

effect of oral retinoids on human activin-A serum levels
in patients with acne.
In this study, serum level of activin-A was associated
significantly with the severity of acne scarring and a cut
off value for the discrimination between those patients
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liable to develop postacne scarring and others not liable
could be detected. Several other studies had been
conducted for the detection of reliable serum
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predictive marker for postacne scarring, for example,
El-Taweel et al. [20], who found that patients who had
postacne scarring expressed a significantly lower level
of hepcidin in the serum and significantly higher levels
of C-reactive protein, and El Mokadem et al. [21], who
detected a higher serum survivin in patients with acne
scars. We think that the combination of multiple serum
biomarkers is needed to increase the accuracy of
prediction of those patients liable to develop acne scars.
Limitations of the study were small number of the cases
and controls and short period of follow up.
Conclusion
Serum level of activin-A could be a good and reliable
marker for the prediction of those patients liable to
develop postacne scarring, but more in-depth studies
are still required to detect the exact pathogenic action
of activin-A in the development of acne scars and to
test the targeting of activin-A in an attempt to prevent
postacne scarring.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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