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Single-cell immunopathology of systemic contact allergy associated with corticosteroids
Journal article   Peer reviewed

Single-cell immunopathology of systemic contact allergy associated with corticosteroids

R. Hertzman, P. Deshpande, K. White, R. Gangula, A. Chopra, R. Ram, S. Leary, J. Zic, J. Zwerner, A. Gibson, …
Journal of Allergy and Clinical Immunology, Vol.147(2), AB31
2021
DOI: https://doi.org/10.1016/j.jaci.2020.12.148
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Abstract

Rationale Allergic contact dermatitis (ACD) is a classic delayed hypersensitivity reaction commonly associated with corticosteroids that can rarely manifest as a delayed rash following systemic administration. Methods A 50-year old woman developed local edema and delayed spreading rash following interarticular injection with dexamethasone and methylprednisolone acetate (MA). 6-months following this intradermal skin testing (IDST) was positive to MA and methylprednisolone sodium succinate, and IDST and patch test negative to other corticosteroids. She tolerated dexamethasone challenge. Cells were isolated from 4-mm punch biopsies from 48-hour positive IDST and unaffected skin with liberase digestion and sorted on CD3. scTCR and scRNA-seq were performed using plate-based assays (Smart-seq-2). Data was filtered using Seurat and analysed with Visual Genomics Analysis Studio (VGAS) software. Results Histopathology showed a superficial perivascular dermatitis with epidermal spongiosis in keeping with ACD. T-cells were 18x more prevalent in affected skin and those from both affected and unaffected sites were predominantly CD8+ T-cells that expressed CD45RO and polyclonal TCR alpha beta. Differentially expressed genes (DEG) in T-cells from affected skin reflected homing (CCR7,S1PR1), T-cell activation and proliferation (TNFRS9, GRAP2, ZYG11A, ZHX1), T-cell effector differentiation (IL-21R), and stress survival (EEF1A1, IFI6) without representation of markers of T-cell residency (ITGAE) or regulation. Conclusions We demonstrate insights into the immunopathogenesis of drug-induced ACD by showing that IDST+ methylprednisolone associated ACD is corticosteroid-specific and associated with a polyclonal population of primarily CD45RO+ memory CD8+ T-cells showing upregulation of markers of homing, T-cell activation, proliferation and differentiation but lacking markers of T-cell residency and regulation.

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