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.

Th17 cells and tissue remodeling in atopic and contact dermatitis

“…Earlier work characterized the immunophenotype of T cells infiltrating the skin in AD and ACD . Recently, Th17 and Th22 have been identified as distinct T‐cell subsets being involved in the pathogenesis of various, including allergic, skin diseases .…”

Systematic, spatial imaging of large multimolecular assemblies and the emerging principles of supramolecular order in biological systems

“…Several reviews and editorials on toponomics have been published, and techniques applying the cyclical toponomics principle of imaging have been reported to address a variety of biological problems in cytometry and cell biology (Bedner et al, 2001;Ecker and Tarnok, 2005;Abott, 2006;Ecker et al, 2006;Laffers et al, 2006;Mittag et al, 2006;Murphy, 2006;Cottingham, 2008;Sage, 2009;Eyerich et al, 2010;Micheva and Bruchez, 2012). A variety of cellular and disease mechanisms, stem cell features, and target molecules have been identified by cyclical imaging, and several toponomic studies have analyzed skin allergies and the binding sites and activity of a therapeutic agent for inflammatory skin disease Ebert et al, 1998;Haars et al, 2000;Bonnekoh et al, 2008Bonnekoh et al, , 2007aBonnekoh et al, , 2007bBonnekoh et al, , 2006Coste et al, 2008;Alex et al, 2009;Berndt et al, 2010;Ruetze et al, 2010;Eckhardt et al, 2013;Ostalecki et al, 2013).…”

WHIDE—a web tool for visual data mining colocation patterns in multivariate bioimages

“…Furthermore, thresholding discards information inherent in the data, so analyzing non-binarized gray value images may be better suited to track protein locations in the cell (Friedenberger et al , 2007). However, the CMP concept has successfully been applied in several studies (Bhattacharya et al , 2010; Bonnekoh et al , 2006; Eyerich et al , 2009; Ruetze et al , 2010), for example revealing proteins controlling the molecular networks of tumor cell lines, or finding CMPs to distinguish between healthy patients, patients with psoriasis and patients with atopic dermatitis. But even regardless of the aforementioned thresholding issue, we believe that the CMP-based visualization concept should be reconsidered as follows.…”