Atopic dermatitis IgG modulates peripheral T-cell responses in vitro and reveals candidate serological reactivities

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease marked by barrier dysfunction and immune dysregulation. Although IgE has been extensively implicated in AD pathogenesis, the functional role of polyclonal IgG remains poorly defined. We investigated whether IgG from adults with AD modulates peripheral immune responses and whether it carries disease-associated serological targets. IgG purified from serum from adults with AD (n = 24), non-atopic controls (n = 20), and atopic individuals without AD (n = 20) was evaluated in peripheral blood mononuclear cell cultures, flow-cytometry assays, descriptive transcriptomic and small-RNA sequencing analyses, short-term membrane-binding experiments, and human proteome microarrays. In vitro exposure to pooled AD IgG was associated with subset-specific changes in CD4+ and CD8+ T-cell phenotype and cytokine frequencies. In CD4+ T cells, AD IgG reduced CD45RA and increased CD45RO, IFN-γ-, IL-10-, and IL-22-producing fractions; in CD8+ T cells, it reduced the IFN-γ-producing fraction. Descriptive analyses of one pooled RNA library per condition identified fold-change patterns involving immune and post-transcriptional pathways but did not support replicate-based differential-expression inference. AD IgG was detected on a small fraction of CD4+ and CD8+ T-cell membranes during a 30-min assay without a contemporaneous increase in Annexin V positivity. Proteome-array screening generated a heterogeneous list of candidate IgG-reactive proteins, many with low signal intensity; a higher-stringency cross-group comparison prioritized CRABP2 as a candidate seroreactivity requiring independent validation. A fixed pooled AD IgG preparation was associated with reproducible in vitro changes in T-cell phenotype and cytokine frequencies across healthy PBMC donors. The pooled omics and proteome-array findings are exploratory and nominate hypotheses and seroreactivities for validation; they do not establish population-level disease specificity, a membrane-binding mechanism, or diagnostic performance.