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SHORT COMMUNICATION
Aberrant B-cell Subsets and Immunoglobulin Levels in Patients with Moderate-to-severe Psoriasis
Katrin KAHLERT 1 , Franziska GRÄN 1 , Khalid MUHAMMAD 2 , Sandrine BENOIT 1 , Edgar SERFLING 2 , Matthias GOEBELER 1 and
Andreas KERSTAN 1
1
Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, DE-97080 Würzburg, and 2 Department of Molecular
Pathology, Institute of Pathology, Julius-Maximilians-University, Würzburg, Germany. E-mail: [email protected]
Accepted Oct 15, 2018; E-published Oct 15, 2018
Psoriasis is a chronic inflammatory disease affecting 2–3%
of the world’s population. Clinically, skin inflammation is
mirrored by infiltrated erythematous papules and plaques
with silver-white scaling. At the cellular level T lympho-
cytes are considered as the key immunological players.
Commonly used and emerging therapeutic strategies
accordingly rely on the inhibition of proinflammatory
cytokines, amongst others tumour necrosis factor (TNF)-α
and interleukin (IL)-17. Although B cells are assumed to
play a role in cutaneous immunity, both in malignancy, e.g.
melanoma (1, 2), and in particular autoimmune skin inflam-
mation, e.g. lupus erythematosus (3), they have been little-
studied in the pathogenesis of psoriasis (4). To elucidate
the potential impact of B cells in psoriasis we performed a
systematic longitudinal analysis of B-cell subpopulations
and corresponding immunoglobulin (Ig) levels.
METHODS
Heparinized peripheral blood was collected from 34 patients (18
males and 16 females, mean age 50.6 ± 15.4 years) with moderate-
to-severe plaque psoriasis defined by a Psoriasis Area and Severity
Index (PASI) ≥10 (mean PASI 15.6 ± 6.1). Patients were naïve to
or off systemic therapy for at least 4 weeks. Longitudinal analyses
were performed on 18 patients who achieved a PASI improvement
of at least 75% upon treatment. Thirty-four healthy volunteers
served as controls (16 men and 18 women, mean age 46.9 ± 15.7
years). Individuals with acute infections and recent vaccinations
were excluded from the study.
Peripheral blood mononuclear cells (PBMC) were isolated by
Ficoll gradient centrifugation. B cell subsets were evaluated using
flow cytometry (BD FACS Canto, Becton Dickinson GmbH, Hei-
delberg, Germany) and differentiated via surface immunolabelling
according to the gating strategy outlined in Fig. S1 1 . IgM, IgA,
IgE and IgG serum levels were measured using cytometric bead
assays (BD Pharmingen Becton Dickinson GmbH).
The experimental protocol was established according to the
Declaration of Helsinki guidelines and approved by the ethics com-
mittee of the University of Würzburg (#254/13). Written informed
consent was obtained from patients and healthy volunteers. Human
material was stored according to the standards of The Interdisci-
plinary Bank of Biomaterials and Data Würzburg (ibdw) at the
University Hospital Würzburg (see: www.ibdw.uk-wuerzburg.de).
Statistical analyses were performed using GraphPad (Prism)
software, version 5.0. Data are presented as mean ± standard
deviation (SD). Unpaired t-test was applied for comparison of
controls and patients. Paired t-test was applied for longitudinal
data. p-values < 0.05 were considered statistically significant.
https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-3069
1
doi: 10.2340/00015555-3069
Acta Derm Venereol 2019; 99: 226–227
RESULTS
Percentages of total B cells were lower in patients with
moderate-to-severe psoriasis compared with healthy indi-
viduals (Fig. S2A 1 ). Further analysis showed significantly
elevated percentages of transitional B cells (trB) in line
with earlier reports (5). Naïve mature B cells (NM) were
moderately increased, memory B cells (M) and total
plasma cells (PC) were significantly lower in patients
with psoriasis. Investigation of PC in detail revealed that
long-lived PC did not differ. However, plasma blasts (PB)
were significantly elevated in individuals with psoriasis,
indicating a pronounced activation of this short-lived Ab-
producing PC subset (Fig. S2B 1 ). In agreement with this,
serum concentrations of IgA, but not of IgG, IgM and IgE,
were significantly increased (Fig. S2C 1 ). This observation
hints at immunological processes in psoriasis that drive
the generation of IgA.
Determination of B-cell subsets upon successful treat
ment (at least 75% reduction in pretreatment PASI) revea-
led a clear shift towards the conditions found in healthy in-
dividuals (Fig. S3A–B 1 ). Most importantly, total PC were
found to be unchanged, but in-depth analysis of the PC
pool showed that short-lived PB decreased significantly,
while long-lived PC increased moderately. Interestingly,
IgA levels remained elevated upon successful treatment
(Fig. S3C 1 ).
DISCUSSION
In peripheral blood of patients with moderate-to-severe
psoriasis altered frequencies of B-cell subsets and altered
serum IgA levels were observed. Upon successful treat-
ment B-cell subsets normalized, whereas the IgA serum
concentration remained elevated. These results favour
the idea that B lymphocytes may play a role during the
generation and/or maintenance of psoriasis.
B cells have largely been neglected in studies of
psoriasis, potentially owing to their limited presence in
involved psoriatic skin. This, however, does not neces-
sarily exclude a role in the pathogenesis: comparative
immunohistochemical analysis of psoriatic plaques and
lesional skin of patients with acute SLE showed both
equally low numbers of B cells (author’s unpublished
observation). Although SLE is undoubtedly considered a
B-cell-driven disease (6–9).
TrB, characterized by CD19 + CD24 hi CD38 hi surface
expression, are assumed to play a role in autoimmune
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