Distinct immune and clinical responses to alcohol-soluble vs. salt-soluble wheat proteins in mice

Abstract

Food hypersensitivity is a growing global public health problem. Wheat has been linked to distinct types of human hypersensitivities with incompletely understood mechanisms. Although wheat proteins (WP) differ in solubility, it is unknown whether alcohol-soluble (AS) and salt-soluble (SS) WP differ in their immune and disease activation properties. Here we tested the hypothesis that AS and SSWP extracted from soft-wheat will elicit distinct types of immune and clinical responses in inbred mice. Groups of BALB/cJ mice weaned onto a plant-protein free diet received IP injections with AS and SSWP (0.01 mg/mouse) along with alum. The WP-specific (S) IgE, IgG1, IgG2a, IgA and total (T) IgE responses were analyzed. Systemic anaphylaxis and mucosal mast cell degranulation response (MMCR) upon IP challenge were quantified by hypothermia shock response (HSR) and elevation of plasma mMCP-1, respectively. Mice were monitored for dermatitis and alopecia. Spleen tissue extracts were used in measuring immune-activation biomarkers. Whereas the SSWP elicited higher titers of SIgA, the ASWP elicited higher titers of SIgE, SIgG1, SIgG2a and higher TIgE levels. The ASWP elicited significantly higher HSR and MMCR. Only ASWP but not SSWP elicited dorsal neck dermatitis lesions in 44% of mice. Alopecia lesions, without inflammation, were noted in 22% of ASWP- and 33% of SSWP-injected mice. Furthermore, ASWP and SSWP elicited distinct patterns of activation of acute-phase response proteins, chemokines, cytokines, growth factors, matrix proteins and signaling proteins. These data provide the first direct evidence that WP fractions that differ in solubility elicit qualitatively distinct immune and clinical reactions in genetically identical mice.