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226 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 This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.