Dissecting susceptibility from exogenous triggers: The model of <em>Alopecia areata</em> and associated inflammatory skin diseases.

BACKGROUND: Alopecia areata (AA) is a T-cell-driven autoimmune disease of the hair follicle and frequently reported to be associated with inflammatory skin diseases (ISD) such as atopic eczema (AE) or psoriasis. Interestingly, AA on the one hand and both AE and psoriasis on the other hand are believed to be driven by mutually antagonistic T-cell subsets. OBJECTIVE: To characterize AA-specific T-cell profiles and inflammatory pattern by intra-individual comparison of AA and coexistent ISD. METHODS: 112 patients with AA were recruited and investigated for coexisting ISD. In-depth analyses were performed in patients with AA and AE (n = 2), AA and psoriasis (n = 1), AA and psoriasis and AE (n = 1) and AA and lichen planus (n = 1), using histology, immunohistochemistry and cytokine staining of T cells isolated from lesional skin. RESULTS: Of 112 AA patients investigated, 23 suffered from an ISD. The prevalence of AE, vitiligo, psoriasis and lichen planus was higher in the investigated AA cohort than in the normal population. The clinical as well as histological phenotype of AA the coexistent ISD were unequivocal. In line with this, T-cell infiltrates were found to be disease-characteristics with AA and lichen planus dominated by CD8+ and IFN-&gamma;+ TNF-&alpha;+ producing T cells while psoriasis lesions in the same patients were dominated by IL-17+ and AE by IL-4+ T cells. CONCLUSION: AA patients have a higher incidence of various T-cell-driven inflammatory skin diseases than the normal population, a phenomenon which might relate to over-activation of skin-homing T cells and to specific immune triggers as the primary cause of inflammation. More importantly, we showed that by using AA as a model disease, our approach of intra-individual comparison of distinct inflammatory responses in the same patient is feasible and offers the unique possibility to gain insights into disease pathogenesis independent from genetic susceptibilities

Is the humoral immunity dispensable for the pathogenesis of psoriasis?

Background Imbalances of T-cell subsets are hallmarks of disease-specific inflammation in psoriasis. However, the relevance of B cells for psoriasis remains poorly investigated. Objective To analyse the role of B cells and immunoglobulins for the disease-specific immunology of psoriasis. Methods We characterized B-cell subsets and immunoglobulin levels in untreated psoriasis patients (n = 37) and compared them to healthy controls (n = 20) as well as to psoriasis patients under disease-controlling systemic treatment (n = 28). B-cell subsets were analysed following the flow cytometric gating strategy based on the surface markers CD24, CD38 and CD138. Moreover, immunofluorescence stainings were used to detect IgA in psoriatic skin. Results We found significantly increased levels of IgA in the serum of treatment-naive psoriasis patients correlating with disease score. However, IgA was only observed in dermal vessels of skin sections. Concerning B-cell subsets, we only found a moderately positive correlation of CD138(+) plasma cells with IgA levels and disease score in treatment-naive psoriasis patients. Confirming our hypothesis that psoriasis can develop in the absence of functional humoral immunity, we investigated a patient who suffered concomitantly from both psoriasis and a hereditary common variable immune defect (CVID) characterized by a lack of B cells and immunoglobulins. We detected variants in three of the 13 described genes of CVID and a so far undescribed variant in the ligand of the TNFRSF13B receptor leading to disturbed B-cell maturation and antibody production. However, this patient showed typical psoriasis regarding clinical presentation, histology or T-cell infiltrate. Finally, in a group of psoriasis patients under systemic treatment, neither did IgA levels drop nor did plasma cells correlate with IgA levels and disease score. Conclusion B-cell alterations might rather be an epiphenomenal finding in psoriasis with a clear dominance of T cells over shifts in B-cell subsets

Is the humoral immunity dispensable for the pathogenesis of psoriasis? (vol 33, pg 115, 2019).

Authorship correction on Is the humoral immunity dispensable for the pathogenesis of psoriasis? Thomas J, Küpper M, Batra R, Jargosch M, Atenhan A, Baghin V, Krause L, Lauffer F, Biedermann T, Theis FJ, Eyerich K, Eyerich S, Garzorz-Stark N. J Eur Acad Dermatol Venereol. 2019 Jan; 33(1): 115–122. https://doi.org/10.1111/jdv.15101. Epub 2018 Jul 2. This corrigendum is to note that the name of Prof. Carsten Schmidt-Weber was inadvertently omitted as an author in the initial version of the paper. Schmidt-Weber CB has been added for his participation and contributions in this project