86 been associated with mucosal reactivity against milk, where the casein protein seems to be a regulator of the inflammatory response.83,84 Anti-Sjögren’s-syndrome-related antigen A antibodies (anti-SS-A/anti-Ro), which are typical anti-nuclear antibodies associated to autoimmunity, were positively associated with an antibody-bound peptide representing thymidine kinase of EBV. Interestingly, this association has previously been described in the context of Sjögren’s syndrome, in which anti-SS-A autoantibodies and higher frequencies of serological EBV reactivation85 are more frequently observed. The strongest association to total cholesterol levels was with an antibody-bound peptide of Haemophilus parainfluenzae strain T3T1. Other bacterial peptides are also enriched with higher cholesterol labels, including Streptococcus or Pseudomonadaceae.We also observed an enrichment of viral peptides, such as rubeola, Pneumoviridae, HSV and EBV. Many intracellular pathogens are known to use cholesterol drafts to successfully infect cells and to impair the regular cholesterol metabolism and the immune system.86 We observed three associations between body-mass index (BMI) and antibody-bound peptides, all of which represented glycoprotein D of human alpha-herpesviruses (HSV-1/HSV-2). Indeed, obesity has previously been associated with a higher prevalence of herpesvirus infections, in particular HSV-1, by promoting human adipogenesis.87 Finally, participants having any allergy (44.5% of participants) showed associations with six different antibody-bound peptides (Figure 4D). Using more detailed questionnaires with information about different allergies such as dust, pollen, food and others (Supplementary Table 1.3), we identified 13 different peptides associated with at least one phenotype. As expected, the strongest association was observed for dust allergy, showing associations with antibody-bound peptides from the house dust mite Dermatophagoides pteronyssinus (FDR = 3.84x10-5). In addition, the most common associations were observed between casein proteins derived from cow, sheep and buffalo milk, which were linked not only with food allergies but with almost all allergy types. Wheat allergens were linked with self-reported dust and pollen allergies. Interestingly, we identified a couple of associations with influenza (higher prevalence with pollen allergy), bacterial flagellin associations with animal allergies and Shigella flexneri with dust allergy. Previous analyses have linked dust mite with bacterial sensitization, although not for these specific lineages.88 Importantly, several of these significant associations represent linkage between common aeroallergens (e.g. pollen and dust) and food allergy (e.g. Triticum aestivum [wheat] and casein), recapitulating the frequent co-occurrence of allergen cross-reactivity.89 Chapter 3
RkJQdWJsaXNoZXIy MjY0ODMw