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Background: Despite impaired humoral response in patients treated with immunosuppressants (ISPs), recent studies found similar severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection compared to controls. One potential explanation is the rapid generation of humoral response on infection, but evidence is lacking., Objectives: We investigated the longitudinal dynamics of the SARS-CoV-2 antibody repertoire after SARS-CoV-2 delta and omicron breakthrough infection in patients with immune-mediated inflammatory diseases (IMIDs) receiving ISP therapy and controls., Methods: As a prospective substudy of the national Target-to-B! (T2B!) consortium, we included IMID patients receiving ISPs therapy and controls who reported SARS-CoV-2 breakthrough infection between July 1, 2021, and April 1, 2022. To get an impression of the dynamics of the antibody repertoire, 3 antibody titers of wild-type RBD, wild-type S, and omicron RBD were measured at 4 time points after SARS-CoV-2 breakthrough infection., Results: We included 302 IMID patients receiving ISPs and 178 controls. Antibody titers increased up to 28 days after breakthrough infection in both groups. However, in IMID patients receiving therapy with anti-CD20 and sphingosine-1 phosphate receptor modulators, antibody titers were considerably lower compared to controls. In the anti-TNF group, we observed slightly lower antibody titers in the early stages and a faster decline of antibodies after infection compared to controls. Breakthrough infections were mostly mild, and hospitalization was required in less than 1% of cases., Conclusions: Most ISPs do not influence the dynamics of the SARS-CoV-2 antibody repertoire and exhibit a rapid recall response with cross-reactive antibody clones toward new virus variants. However, in patients treated with anti-CD20 therapy or sphingosine-1 phosphate receptor modulators, the dynamics were greatly impaired, and to a lesser extent in those who received anti-TNF. Nevertheless, only a few severe breakthrough cases were reported., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The role of regulatory T cells has been widely reported in the suppression of T-cell activation. A dysfunction in CD4(+)CD25(+) T-regulatory cell-specific transcription factor FoxP3 leads to immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome, often associated with atopic dermatitis. Increasing the number and activity of regulatory T cells in affected organs has been suggested as a remedy in various inflammatory diseases, including allergy., Objective: To determine the presence and function of regulatory T cells in atopic dermatitis., Methods: Immunohistochemistry of lesional atopic dermatitis skin and control skin conditions was used to demonstrate regulatory cells and cytokines in situ. The role of effector and regulatory T cells as well as their specific cytokines in apoptosis in human keratinocyte cultures and artificial skin equivalents was investigated., Results: Human T-regulatory type 1 cells, their suppressive cytokines, IL-10 and TGF-beta, as well as receptors for these cytokines were significantly expressed, whereas CD4(+)CD25(+)FoxP3(+) T-regulatory cells were not found in lesional and atopy patch test atopic dermatitis or psoriasis skin. Both subsets of regulatory T cells suppress the allergen-specific activation of T(H)1 and T(H)2 cells. In coculture and artificial skin equivalent experiments, subsets of T-regulatory cells neither induced keratinocyte death nor suppressed apoptosis induced by skin T cells, T(H)1 cells, IFN-gamma, or TNF-alpha., Conclusion: A dysregulation of disease-causing effector T cells is observed in atopic dermatitis lesions, in association with an impaired CD4(+)CD25(+)FoxP3(+) T-cell infiltration, despite the expression of type 1 regulatory cells in the dermis.

Background: Tissue infiltration of CD4(+) T cells plays an important role in the pathogenesis of allergic diseases. T-cell trafficking is mediated by specific chemokines and their receptors., Objective: The purpose of this study was to investigate the participation of the chemokines thymus and activation-regulated chemokine (TARC) and cutaneous T cell-attracting chemokine (CTACK) in a large population of patients with allergic diseases., Methods: Serum TARC and CTACK levels were measured in 455 patients with allergic disease. Patients were characterized as having atopic dermatitis (AD), allergic asthma, allergic rhinitis, or combinations or as healthy control subjects. Serum TARC and CTACK levels were correlated with disease activity in patients with AD. Furthermore, in 7 patients with AD, serum TARC and CTACK levels were studied after the start of systemic cyclosporin A treatment. Finally, TARC and CTACK localization was checked by immunohistochemistry in lesional skin biopsy specimens of patients with AD., Results: Both TARC and CTACK serum levels in patients with AD were significantly higher than those in healthy control subjects and patients with allergic respiratory disease. Furthermore, serum TARC and CTACK levels significantly correlated with disease activity in patients with AD. Serum TARC levels paralleled clinical improvement in patients treated with cyclosporin A. Immunoreactive TARC was found in infiltrating cells and endothelial cells of the dermis but not in epidermal cells., Conclusions: The serum TARC level is an objective parameter for disease severity specific for AD. Furthermore, it is a promising tool for treatment monitoring.