10.5826/dpc.1302a134
Introduction: Psoriasis is an immune-mediated, chronic and inflammatory disease whose pathogenesis is affected by the interactions of several immune cells and cytokines. PD-1 is an inhibitor receptor that is expressed to a large extent in T lymphocytes and responsible for regulating autoimmunity and self-tolerance.
Objectives: In this study, we aimed to investigate the expression of PD-1/PD-L molecules in the lesioned skins of psoriasis patients.
Methods: The study included 30 psoriasis patients, and 15 healthy volunteers as the control group. Anti PD-1 and PD-L1 antibodies were applied to the skin biopsy samples that were collected from the patient and control groups. Cytoplasmic and membranous staining of PD-1 and PD-L1 were considered positive. The number of stained immune cells that was examined for each case.
Results: The percentage of the tissues with high PD-1 (+) and PDL-1 (+) immune cell counts were significantly higher in the psoriasis patients compared to healthy controls (P values = 0.004 and 0.002, respectively). A negative and statistically significant correlation was detected between PDL-1(+) immune cell numbers and PASI scores (P = 0.033, r=-0.57).
Conclusions: In the lesioned skin samples of psoriasis patients, the PD-1 and PD-L1 expressions were significantly higher in immune cells than that in the skin samples of the healthy controls. This study was the first investigation of the expression of PD-1/PD-L molecules in the immune cells in found the lesioned skins of psoriasis patients.
text/xml
2160-9381
2863
en
Tuce Özkara Duman
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
psoriasis
Investigation of the PD-1/PD-L1 Expression in the Lesional Skins of Patients with Psoriasis
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2023-04-29
2022-09-23
2023-04-29
2023-06-05
e2023134
Dermatol Pract Concept
Introduction: Psoriasis is an immune-mediated, chronic and inflammatory disease whose pathogenesis is affected by the interactions of several immune cells and cytokines. PD-1 is an inhibitor receptor that is expressed to a large extent in T lymphocytes and responsible for regulating autoimmunity and self-tolerance.
Objectives: In this study, we aimed to investigate the expression of PD-1/PD-L molecules in the lesioned skins of psoriasis patients.
Methods: The study included 30 psoriasis patients, and 15 healthy volunteers as the control group. Anti PD-1 and PD-L1 antibodies were applied to the skin biopsy samples that were collected from the patient and control groups. Cytoplasmic and membranous staining of PD-1 and PD-L1 were considered positive. The number of stained immune cells that was examined for each case.
Results: The percentage of the tissues with high PD-1 (+) and PDL-1 (+) immune cell counts were significantly higher in the psoriasis patients compared to healthy controls (P values = 0.004 and 0.002, respectively). A negative and statistically significant correlation was detected between PDL-1(+) immune cell numbers and PASI scores (P = 0.033, r=-0.57).
Conclusions: In the lesioned skin samples of psoriasis patients, the PD-1 and PD-L1 expressions were significantly higher in immune cells than that in the skin samples of the healthy controls. This study was the first investigation of the expression of PD-1/PD-L molecules in the immune cells in found the lesioned skins of psoriasis patients.
Tuce Özkara Duman
2023/04/29
10.5826/dpc.1302a134
e2023134
Yildirim Beyazit University, Medical School, Department of Dermatology, Ankara, Turkey
2160-9381
psoriasis
en
e2023134
Bommarito D, Hall C, Taams LS, Corrigall VM. Inflammatory cytokines compromise programmed cell death-1 (PD-1)-mediated T cell suppression in inflammatory arthritis through up-regulation of soluble PD-1. Clin Exp Immunol. 2017;188(3):455-466. DOI: 10.1111/cei.12949. PMID: 28245522. PMCID: PMC5422858.
Investigation of the PD-1/PD-L1 Expression in the Lesional Skins of Patients with Psoriasis
https://dpcj.org/index.php/dpc/article/download/2863/2073
   Investigation of the PD-1/PD-L1 Expression in the
       Lesional Skins of Patients With Psoriasis
         Selma Emre1, Nuran Süngü2, Yıldız Hayran3, D Deniz Demirseren4, Akın Aktas1,
                                    Tuce Özkara Duman1


1 Yildirim Beyazit University, Medical School, Department of Dermatology, Ankara, Turkey
2 Yildirim Beyazit University, Medical School, Department of Pathology, Ankara, Turkey
3 Ministry of Health, Ankara City Hospital, Department of Dermatology, Ankara, Turkey
4 University of Health Science, Ankara City Hospital, Department of Dermatology, Ankara, Turkey



Key words: autoimmunity, immunohistochemistry, PD1, PDL-1, psoriasis
Citation: Emre S, Süngü N, Hayran Y, Demirseren DD, Aktas A, Duman TÖ. Investigation of the PD-1/PD-L1 Expression in the Lesional
Skins of Patients with Psoriasis. Dermatol Pract Concept. 2023;13(2):e2023134. DOI: https://doi.org/10.5826/dpc.1302a134
Accepted: November 17, 2022; Published: April 2023
Copyright: ©2023 Emre et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding author: Selma Emre, Yildirim Beyazit University, Medical School, Department of Dermatology, Ankara City Hospitals,
Orthopedics and Neurology Hospital, Cankaya, Ankara, Turkey. ORCID number: 0000-0001-5963-8939 E-mail: dr_semre@yahoo.com




  ABSTRACT             Introduction: Psoriasis is an immune-mediated, chronic and inflammatory disease whose pathogene-
                       sis is affected by the interactions of several immune cells and cytokines. PD-1 is an inhibitor receptor
                       that is expressed to a large extent in T lymphocytes and responsible for regulating autoimmunity and
                       self-tolerance.
                       Objectives: In this study, we aimed to investigate the expression of PD-1/PD-L molecules in the
                       ­lesioned skins of psoriasis patients.
                       Methods: The study included 30 psoriasis patients, and 15 healthy volunteers as the control group.
                       Anti PD-1 and PD-L1 antibodies were applied to the skin biopsy samples that were collected from the
                       patient and control groups. Cytoplasmic and membranous staining of PD-1 and PD-L1 were consid-
                       ered positive. The number of stained immune cells that was examined for each case.
                       Results: The percentage of the tissues with high PD-1 (+) and PDL-1 (+) immune cell counts were
                       significantly higher in the psoriasis patients compared to healthy controls (P values = 0.004 and 0.002,
                       respectively). A negative and statistically significant correlation was detected between PDL-1(+)
                       ­
                       ­immune cell numbers and PASI scores (P = 0.033, r=-0.57).
                       Conclusions: In the lesioned skin samples of psoriasis patients, the PD-1 and PD-L1 expressions were
                       significantly higher in immune cells than that in the skin samples of the healthy controls. This study
                       was the first investigation of the expression of PD-1/PD-L molecules in the immune cells in found the
                       lesioned skins of psoriasis patients.




Original Article | Dermatol Pract Concept. 2023;13(2):e2023134                                                                      1
Introduction                                                     have investigated the expression of PD-1 and PD-L in the
                                                                 T lymphocytes of the peripheral blood of psoriasis patients.
Psoriasis is an immune-mediated, chronic and inflammatory        Even fewer studies investigate the expression of PD-1 and
disease whose pathogenesis is affected by the interactions of    PD-L1 in the lesional skins of psoriatic patients.
several immune cells and cytokines. Over the last two de-
cades, highly significant advancements have been achieved
regarding the pathogenetic mechanisms of psoriasis where T
                                                                 Objectives
helper 1 (Th1) and Th 17 lymphocytes play a major role [1].1     In this study, we aimed to investigate the expression of
Recently, new molecules and pathways responsible for reg-        PD-1/PD-L molecules in the lesional skins of psoriasis
ulating autoimmunity and tolerance have been defined. One        patients.
of these molecules, programmed death-1 (PD-1) (CD279) is
an immune check point that sends inhibitor signals to the im-
mune system to maintain a balance between T cell activation      Methods
and self-tolerance in peripheral tissues. PD-1 is an inhibi-
                                                                 Thirty psoriasis patients aged between 18 and 70 years who
tor receptor in the form of a transmembrane glycoprotein
                                                                 were admitted to the dermatology outpatient clinic were in-
that belongs to the CD28/CTLA-4 family with the weight
                                                                 cluded in the study. Skin biopsy specimens of the patients
of 50-55 kDa. PD-1 is expressed in active T cells, B cells,
                                                                 who were histopathologically diagnosed with psoriasis, and
thymocytes, natural killers (NK) and double negative thymo-
                                                                 had the appropriate characteristics for the study, were in-
cytes (CD4ˉCD8ˉ). PD-1 has two ligands: Inhibitor signals
                                                                 cluded in the immunohistochemical study. Those who had
are achieved by the bonding of PD-1 to its ligands – PD-1
                                                                 another autoimmune disease such as Type 1 diabetes melli-
ligand 1 (PD-L1) and PD-1 ligand 2 (PD-L2). While PD-L1
                                                                 tus, inflammatory bowel disease, rheumatoid arthritis, sys-
is widely expressed in T cells, B cells, macrophages and den-
                                                                 temic lupus erythematosus, ankylosing spondylitis, vitiligo,
dritic cells, PD-L2 is expressed in active macrophages and
                                                                 alopecia areata or encephalomyelitis were excluded. None
dendritic cells. The PD-1/PD-L pathway participates in the
                                                                 of the patients included in the study, had any malignity or
pathogenesis of autoimmune diseases. Signals that are gen-
                                                                 was being treated with anti-PD-1 molecules for malignity.
erated by PD-1 and its ligands, PD-L1 and PD-L2, regulate
                                                                 Intact skin biopsy samples of healthy volunteers aged 19 to
central and peripheral tolerance by means of several mecha-
                                                                 60 years who did not have any disease were included in the
nisms [2-4]. In experimental autoimmunity and pathogenic
                                                                 study as the control group. All participants were informed
polymorphism models, it was seen that a decrease in the
                                                                 about the study and their written consent was obtained prior
expression of PD-1 and its ligands is associated with some
                                                                 to their enrollment in the study. Before starting the study,
autoimmune disorders such as Type 1 diabetes mellitus, in-
                                                                 approval was received from the local ethics board of our
flammatory bowel disease, rheumatoid arthritis, systemic
                                                                 hospital with the decision date 05.03.2018 and number 52.
lupus erythematosus, ankylosing spondylitis, and encepha-
                                                                    The skin biopsy samples collected from the patients were
lomyelitis [2,3].
                                                                 put into formalin solutions. After formaldehyde fixation, the
    Regulatory T-cells (Treg) is a T-cell subtype responsible
                                                                 tissues were embedded in paraffin. Four cross-sections were
for suppressing the immune response and maintaining im-
                                                                 taken from the paraffin blocks. One of the cross-sections
mune tolerance. PD-1 surface molecules on the surface of
                                                                 was stained with H&E. The diagnosis of psoriasis was histo-
Treg cells play a key role in immune tolerance. PD-1 binds
                                                                 pathologically confirmed by the H&E cross-sections.
to PD-L1, inhibiting the function of the effector T-cells and
supporting the Treg cells activity. Likely to be dysfunctional
in psoriatic patients, T-cell surface molecules are unable to    Immunohistochemical Study Procedure
inhibit the activity of the inflammatory cells [4,5]. In addi-   All cases were applied, a 1/250 dilution rate of anti PD-1
tion, the PD-1 and PDL-1 pathways are among the most im-         antibody (ab137132, abcam), 1/200 dilution rate of anti
portant mechanisms in tumor cells escape from the immune         PD-L1 antibody (ab205921, abcam) and 1/100 dilution
system. PD-L1 expression of tumors is a key determinant          rate of anti PD-L2 antibody (ab200377, abcam). From the
of the response to immune check point inhibitors. It was         formalin-fixed paraffin blocks, 3-4-μ-thick sections were
reported that, in patients treated with anti-PD-1 molecules,     prepared on slides coated with poly-L-lysine.
eczema, lichenoid dermatoses, vitiligo and psoriasis lesions        The cross-sections were left overnight in a stove at 37-40 °C,
emerged, or previously existing psoriasis became more se-        and in the morning, they were kept in a stove at 65 °C for
vere [7-9]. The fact that anti-PD-1/PD-L1 antibodies trigger     45 minutes so that the paraffin could melt. The cross sections
psoriasis suggests that PD-1 and PD-L1 pathways are some-        were then kept in xylol for 20 minutes to deparaffinize. They
how involved in the pathogenesis of psoriasis. Few studies       were rehydrated in alcohol and hydrated in distilled water.



2                                                                    Original Article | Dermatol Pract Concept. 2023;13(2):e2023134
    In the immunohistochemical staining process that was               of PD-1 and PD-L1 positive immune cell <10) and tissues
carried out using a Leica Bond-Max automated immunohis-                with high PD-1 and PD-L1 (+) immune cell counts (number
tochemical staining device, the slides were boiled in water            of PD-1 and PD-L1 positive immune cells ≥10)
containing a citrate buffer (pH 6.0) solution at 95-99 °C for
10 minutes to recover the antigen before applying the anti-            Statistical Analyses
body. They were then left to cool at room temperature for              All statistical analyses were conducted using IBM Statistical
15-20 minutes. The slides were washed with distilled water,            Package for the Statistical Package for the Social Sciences
treated with 3% hydrogen peroxide for 15 minutes at room               (SPSS) version 23.0 (IBM SPSS Corp.). Categorical variables
temperature to block endogenous peroxidase activity, and put           were presented as frequency and percentage. Visual methods,
in distilled water once more. Superblock was dripped on the            Kolmogorov–Smirnov test and Shapiro-Wilk test were used
cross-sections which were washed with PBS (0.01 M Phos-                to evaluate if the numerical variables were normally distrib-
phate Buffer Saline) and left for 3-5 minutes. Then, primary           uted. Normally distributed variables were presented as mean
antibodies were dripped on the cross sections, which were              (standard deviation, SD) and continuous variables which
left for 30-45 minutes. Following the PBS washing process,             were not normally distributed were presented as median (in-
the cross-sections were kept at room temperature for 20 min-           terquartile range, IQR). Categorical variables were analyzed
utes by dripping biotinylated secondary antibodies, and then,          using chi-squared test or Fischer exact and numerical vari-
washed with PBS for 5 minutes. Conjugated streptavidin en-             ables were analyzed using Student t-test or Mann–Whitney
zyme was dripped on the cross-sections, which were kept at             U test. Spearman and Pearson tests were used to evaluate the
room temperature for 10 minutes, and washed again with                 correlations of continuous variables. The level of statistical
PBS. Later, DAM chromogen was dripped, and the cross-sec-              significance was accepted as P < 0.05.
tions were washed with distilled water. ­Following a prelimi-
nary staining with Harris Hematoxylin for 10 seconds, and
                                                                       Results
washing with distilled water, the slides were dried by dipping
into alcohol and coated with balm.                                     Among the patients in the study, 22 were male, 8 were female.
                                                                       Among the individuals in the control group, 13 were f­ emale,
Analysis of the Immunohistochemical                                    2 were male. The mean age of the patients was 40.07 ±
Study Results                                                          16.99, the mean age of the control group was 44.13 ± 12.35,
Anti PD-1 and PD-L1 antibodies were applied on the                     and there was no significant difference between the groups
cross-sections obtained from the prepared paraffin blocks.             in terms of age (P = 0.415) (Table 1).
Cytoplasmic and membranous staining of PD-1 and PD-L1                      For all the samples studied, only the immune cells in
was considered positive. The number of the stained immune              the dermis showed positive staining with PD-1 and PDL-1.
cells was examined, counted and recorded for each case. Ad-            ­Epidermis did not show any staining. 86.7% of the psoriasis
ditionally, tissues were divided into two groups according to          patients had high PD-1 (+) immune cell counts (Figure 1).
their PD-1 and PD-L1 positive immune cell counts: Tissues              In the control group, 40% of the tissues had high PD-1 (+)
with low PD-1 and PD-L1 (+) immune cell counts (number                 immune cell counts, which was significantly lower than the


 Table 1. Basic characteristics of patient and control groups, comparison of PD-1 and PDL-1 results.
                                                             Patients (N = 30)          Controls (N = 15)              P
 Age (years, mean ± SD)                                          40.07±16.99               41.13±12.35               0.415
 Gender (n (%))
   Female                                                          8 (26.7)                    13 (86.7)            <0.001
   Male                                                           22 (73.3)                     2 (13.3)
 PASI (median (IQR))                                             5.4 (4.6-6.9)                     -                    -
 Disease duration (years, median (IQR))                           2 (1.5-9)                        -                    -
 PD-1 positive cell number (n (%))
   Low (<10)                                                       4 (13.3)                     9 (60)
   High (≥10)                                                     26 (86.7)                     6 (40)               0.004
 PDL-1 positive cell number (n (%))
   Low (<10)                                                      17 (56.7)                    15 (100)
   High (≥10)                                                     13 (43.3)                     0 (0)                0.002

IQR = interquartile range; PASI: Psoriasis Area and Severity Index; SD = standard deviation.



Original Article | Dermatol Pract Concept. 2023;13(2):e2023134                                                                     3
Figure 1. Positive staining of more than 10 cells is present in the
immune cells in the upper dermis under the epidermis (PD-1, x400).



psoriasis patients (P = 0.004). Similarly, the percentage of the
tissues with high PDL-1 (+) immune cell counts was signifi-
cantly higher in the psoriasis patients compared to healthy           Figure 2. Positive staining is present in more than 10 cells in the im-
                                                                      mune cells of the upper dermis under the epidermis (PD-L1, x400).
controls (43.3% versus 0%, P = 0.002) (Figure 2).
    The median PASI score was calculated as 5.4 (IQR:
4.6-6.9) and the median disease duration was 2 years (IQR:
1.5-9). A negative and statistically significant correlation          while stimulation of the PD-1 pathway inhibited the Th-1/
was detected between PASI scores and PDL-1 (+) immune                 Th17-mediated cutaneous reactions [6,11].
cell counts (P = 0.033, r = -0.57). There was no significant              High-affinity anti-PD-1 or anti-PD-L1 monoclonal anti-
correlation between PASI scores and PD-1 (+) immune cell              bodies that block the PD-1 and PD-L1 interaction may elim-
counts (P = 0.51, r = -0.19). Disease duration did not cor-           inate the control mechanism over T cells by reversing the
relate with the PD-1 (+) immune cell counts or PDL-1 (+)              immune control point. In recent years, anti-PD-1 antibodies
immune cell counts (P = 0.43, r = 0.29; P = 0.61, r = 0.19,           have been used in cancer treatment, controlling tumor pro-
respectively).                                                        gression and mobilizing the immune system. Using anti-PD-1
    Among psoriasis patients, one patient had pustular psori-         antibodies for treatment has brought about some side effects.
asis, one had guttate and one had palmoplantar psoriasis. All         Skin toxicity is the most frequently observed side effect en-
three patients had high PD-1 (+) immune cell counts how-              countered in anti-PD-1 treatments. Some skin diseases such
ever PDL-1 (+) immune cell counts differed with subtype.              as vitiligo, photosensitivity, lichenoid eruption and psoria-
Patient with pustular psoriasis had high PDL-1 (+) immune             sis were triggered in patients, on whom the anti-PD-1 anti-
cell counts whereas patients with guttate and palmoplantar            body was used. In the literature, lichenoid reactions, eczema,
psoriasis had low PDL-1 (+) immune cell counts.                       pruritus and vitiligo are reported as the most frequently
                                                                      encountered cutaneous side effects [7,9,12,13]. Psoriasis is

Conclusions                                                           a well-established side effect secondary to PD-1 and PD-
                                                                      L1 blockade, and the number of anti-PD-1-induced psori-
PD-1 is an inhibitor receptor that is highly expressed in T lym-      asis cases in the literature continues to increase [8,14-17].
phocytes. When the PD-1 pathway is activated, its inhibiting          How the PD-1/PD-L1 pathway affects psoriasis or other skin
effect on the immune system emerges [10]. It was reported in          diseases is unknown. In patients receiving anti-PD-1 ther-
previous studies that the PD-1 signal pathway regulates the           apy, PD-1 blockade may be inducing a pro-inflammatory
production of cytokines such as INF, IL-2, IL-17, and TNF-α,          Th-1/Th-17 response by increasing interferon-gamma, tu-
thus regulating the axes of PD-1, Th1, and Th17. In murine            mor necrosis factor-alpha (TNF-alpha), and IL-2, IL-6, and
models, PD-1 deficiency induced psoriasiform dermatitis               IL-17 [17].



4                                                                          Original Article | Dermatol Pract Concept. 2023;13(2):e2023134
    A few studies have been conducted to investigate PD-1           In our study, we examined PD-1 and PD-L1 expression
and PD-L1 expression in the T lymphocytes in the periph-         in the immune cells in the epidermis and dermis. There was
eral blood of psoriasis patients. Bartosinska et al examined     no PD-L1 and PD-1 expression in the keratinocytes in pso-
the PD-1 expressions in the CD4+ and CD8+ T-cells in the         riatic skin and healthy controls. In patient group, we found
peripheral blood samples of the patients with psoriasis and      the PD-1 and PD-L1 expression in the immune cells in the
psoriatic arthritis [18]. They concluded that the PD-1 expres-   dermis of psoriatic skin to be significantly higher in com-
sion in the CD4+ and CD8+ T lymphocytes of the patient           parison to the healthy controls. Since PD-1 is an inhibitor
group was significantly lower than the controls. The authors     co-receptor in the immune system, it may seem unreason-
argued that reduced PD-1 expression may be responsible for       able that its expression increases in autoimmune diseases,
immune dysregulation in the pathogenesis of psoriasis. In a      whereas studies in autoimmune diseases including SLE and
later study of theirs, Bartosinska et al reported that there     rheumatoid arthritis show that the PD-1/PD-L1 pathway is
was no difference between psoriatic patients with and with-      modulated under the permanent chronic inflammation con-
out PsoA in terms of CD4+ and CD8+ T lymphocytes PD-1            ditions [5]. It is reported that T-cells express higher amounts
in peripheral blood, and both groups had lower CD4+ and          of PD-1 in autoimmune diseases, neoplasms and chronic in-
CD8+ PD-1 levels than the healthy controls [19]. The au-         fections, limiting the protective immunity. In addition, since
thors stated that, regardless of the clinical type, mutual in-   PD-1 is also a marker of the T-cell activation, it is not sur-
flammatory pathways and mediators play a role in psoriasis.      prising to see that it is increased in psoriatic lesions [23].
In contrast, Peled et al reported that the PD-1 expression          In this study, we also evaluated the association of clinical
in the T lymphocytes in the peripheral blood of psoriatic        features such as disease duration and PASI scores of psori-
arthritis patients was significantly higher than the healthy     asis patients with PD-1 and PD-L1 expressions. Our results
controls [10]. They showed that this was correlated with the     showed a significant negative correlation between PDL-1 (+)
activity of arthritis. The authors argued that PD-1 could be     immune cell counts and PASI. PDL-1 (+) immune cell counts
a marker that shows psoriatic arthritis activity. Bommarito      did not correlate with disease duration. PD-1 (+) immune
et al showed that Rheumatoid arthritis (RA) and psoriatic        cell counts did not correlate with PASI or disease duration.
arthritis (PsoA) patients had an increased expression of PD1     Few studies investigated the association of clinical features
on their CD4+ and CD8+ T cells in their peripheral blood         with PD-1 and PD-L1 expressions. In the study by Peled et
and sinovial fluids [20]. The authors showed that IL-1β, IL-6,   al, no statistically significant correlation was shown among
and TNF-α raised the soluble PD-1 levels, and that increased     the percentage of PD-1 expressing T cells and PASI scores of
expression of soluble PD-1 interfered with the PD-1/PD-L1        patients but the percentage of PD-1 expressing T cells neg-
pathway.                                                         atively correlated with psoriatic arthritis articular disease
    Few studies investigate the PD-1 and PD-L1 expression in     activity [10]. Jung et al showed that psoriasis patients with
the lesional skins of psoriatic patients and reported variable   high epidermal PD-1 expression had higher PASI scores and
results. Kim et al showed that the PD-L1 expression in ke-       longer disease durations [20]. However, dermal PD-1 ex-
ratinocytes in psoriatic epidermis was significantly reduced     pression and disease duration had an opposite relationship.
compared to normal skin, pityriasis rosea, liken planus and      Psoriasis patients with lower PD-1 expressions had longer
allergic contact dermatitis epidermis samples [21]. The au-      disease durations. Dermal PD-1 expression did not correlate
thors suggested that T cell activation was not suppressed due    with PASI. These differences between the results of the stud-
to the reduced PD-L1 and 2 in psoriasis. On the other hand,      ies may be due to the small number of patients included in
Jung et al. [20] reported that among the chronic plaque-type     the studies, the fact that the presence of psoriatic arthritis
psoriatic patients, the group with a higher PD-1 in epidermis    was not considered in every study, different sides of the PD-1
had a higher PASI score and more typical histopathological       and PDL-1 positivity (epidermal or dermal area), and the
changes than the lower PD-1 expression group. Authors sug-       low PASI scores of the patients included in the studies.
gested that epidermal PD-1 upregulation in chronic plaque           This study showed that, the PD-1 and PD-L1 expressions
psoriasis is correlated with a more chronic and severe dis-      in immune cells in the lesioned skin samples of psoriasis pa-
ease. They showed that guttate psoriatic patients with a lon-    tients are significantly higher than that in the skin samples of
ger disease duration had a lower dermal PD-1 expression          healthy controls. Previous studies and our study are prelim-
than those with a shorter disease duration, and downreg-         inary studies with small numbers of patients with psoriasis.
ulated dermal PD-1 expression is correlated with a poorer        To the best of our knowledge, the present study is one the
prognosis in guttate psoriasis. Çetinözman, et al also found     first investigations of the expression of PD-1/PD-L molecules
increased levels of PD-1 in the CD8+ T-cells in the epidermis    in the immune cells in the lesioned skins of psoriasis patients.
and dermis of the skin biopsies taken from the lesions of 6      The role that the degradation of the PD-1/PD-L1 axis plays
patients with psoriatic erythroderma [22].                       in psoriatic patients is backed by evidence. However, there is



Original Article | Dermatol Pract Concept. 2023;13(2):e2023134                                                                    5
not ample evidence and the results of the present study are              11. Fujiwara H, Maeda Y, Kobayashi K, et al. Programmed Death-1
not sufficient for a thorough understanding of the subject                   Pathway in Host Tissues Ameliorates Th17/Th1-Mediated Ex-
                                                                             perimental Chronic Graft-versus-Host Disease. J Immunol.
matter. For a better understanding of this subject, it is neces-
                                                                             2014;193(5):2565-2573. DOI: 10.4049/jimmunol.1400954.
sary to investigate the PD-1 and PD-L1 expressions in pso-
                                                                             PMID: 25080485.
riasis patients with reference to the studies conducted with             12. Hwang SJE, Carlos G, Wakade D, et al. Cutaneous adverse
more patients and employing more detailed research designs.                  events (AEs) of anti-programmed cell death (PD)-1 therapy in
We believe that this may unearth new pathways in the patho-                  patients with metastatic melanoma: A single-institution cohort.
genesis of psoriasis. In the future, medications modulating                  J Am Acad Dermatol. 2016;74(3):455-461.e1. DOI: 10.1016/j.
                                                                             jaad.2015.10.029. PMID: 26793994.
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                                                                         13. Sibaud V. Dermatologic Reactions to Immune Checkpoint Inhib-
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                                                                             itors: Skin Toxicities and Immunotherapy. Am J Clin Dermatol.
      PD-1 and PD-L1 expressions in the immune cells in                      2018;19(3):345-361. DOI: 10.1007/s40257-017-0336-3. PMID:
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the healthy controls. Increased immune system activity in the            14. Voudouri D, Nikolaou V, Laschos K, et al. Anti-PD1/PDL1 in-
psoriatic lesions may trigger PD-1 and PD-L1 expression in                   duced psoriasis. Curr Probl Cancer. 2017;41(6):407-412. DOI:
                                                                             10.1016/j.currproblcancer.2017.10.003. PMID: 29096940.
the immune cells of the lesioned skin.
                                                                         15. Kato Y, Otsuka A, Miyachi Y, Kabashima K. Exacerbation of
                                                                             psoriasis vulgaris during nivolumab for oral mucosal melanoma.
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6                                                                              Original Article | Dermatol Pract Concept. 2023;13(2):e2023134
