title: Comparative in situ topoproteome analysis reveals differences in patch test-induced eczema: cytotoxicity-dominated nickel versus pleiotrope pollen reaction.
abstract: A subgroup of patients with atopic eczema develops acute eczematous reactions to type I allergy-inducing agents such as pollen that clinically resemble type IV allergies induced by haptens like metal ions. To clarify the underlying immunologic mechanisms, this study was designed to map the inflammatory in situ topoproteome of eczematous responses to grass/birch pollen and nickel by using atopy patch test (APT) and nickel patch test (NPT) as an appropriate clinical model, respectively. Biopsies from NPT (n = 6) and APT (n = 6) with positive reactions at 72 h were analysed by multiple epitope ligand cartography (MELC), which enabled to investigate coexpression of 49 different epitopes immunohistochemically in a single given tissue section. Colocalisation of IgE and FcepsilonRI was investigated by confocal microscopy. Compared with APT responses, NPT reactions were dominated by cytotoxic TIA-1 + and CD8 + T cells. In contrast, the immune response in APT reactions appeared more pleiotrope - as detected by colocalisation analysis. Multiple combinatorial molecular phenotype (CMP) motifs containing naive, early maturation and memory T cell (CD45RA, CD7, CD44, CD45R0), and general activation markers (CLA, HLA-DR, CD13, CD29, CD58, CD71, CD138) were significantly higher expressed in APT when compared with NPT reactions. APT response was confirmed to be accompanied by IgE bound to FcepsilonRI. In summary, our results demonstrate that the NPT reaction is clearly dominated by cytotoxic events, while the APT reaction to pollen grains is more heterogeneous and elicits a combined humoral and cellular immune reaction.
authors.affiliation: ZAUM - Center for Allergy and Environment, Division of Environmental Dermatology and Allergy, Helmholtz Zentrum/TUM, Munich, Germany.
authors.forename: Kilian
authors.initials: K
authors.lastname: Eyerich
authors.forename: Raik
authors.initials: R
authors.lastname: Böckelmann
authors.forename: Ansgar J
authors.initials: AJ
authors.lastname: Pommer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Foerster
authors.forename: Henning
authors.initials: H
authors.lastname: Hofmeister
authors.forename: Johannes
authors.initials: J
authors.lastname: Huss-Marp
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavani
authors.forename: Heidrun
authors.initials: H
authors.lastname: Behrendt
authors.forename: Johannes
authors.initials: J
authors.lastname: Ring
authors.forename: Harald
authors.initials: H
authors.lastname: Gollnick
authors.forename: Bernd
authors.initials: B
authors.lastname: Bonnekoh
authors.forename: Claudia
authors.initials: C
authors.lastname: Traidl-Hoffmann
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001706:Biopsy; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002452:Cell Count; D002465:Cell Movement / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D017449:Dermatitis, Allergic Contact / Q000276:immunology; D003876:Dermatitis, Atopic / Q000276:immunology; D004485:Eczema / Q000276:immunology*; D006681:HLA-D Antigens / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology*; D007073:Immunoglobulin E / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D009532:Nickel / Q000276:immunology*; D010328:Patch Tests; D011058:Pollen / Q000276:immunology*; D039102:Poly(A)-Binding Proteins / Q000378:metabolism; D020543:Proteome / Q000276:immunology* / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000074019:T-Cell Intracellular Antigen-1; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015815:Cell Adhesion Molecules; D006681:HLA-D Antigens; D039102:Poly(A)-Binding Proteins; D020543:Proteome; D019253:Proto-Oncogene Proteins c-bcl-2; D017455:Receptors, IgE; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D007073:Immunoglobulin E; D009532:Nickel