A Functional Idiotype/Anti-Idiotype Network Is Active in Genetically Gluten-Intolerant Individuals Negative for Both Celiac Disease-Related Intestinal Damage and Serum Autoantibodies

Sara Quaglia, Fortunato Ferrara, Luigina De Leo, Fabiana Ziberna, Serena Vatta, Serena Marchiò, Daniele Sblattero, Alessandro Ventura, Tarcisio Not

Research output: Contribution to journalArticlepeer-review

Abstract

An unbalance between Abs that recognize an autoantigen (idiotypes; IDs) and Igs that bind such Abs (anti-IDs) is considered a functional event in autoimmune disorders. We investigated the presence of an ID/anti-ID network in celiac disease (CD), a condition in which antitissue transglutaminase 2 (TG2) Abs are suspected to contribute to CD pathogenesis. To characterize the ID side, we reproduced by in vitro yeast display the intestine-resident Abs from CD and control patients. These TG2-specific IDs were used to identify potential anti-IDs in the serum. We observed elevated titers of anti-IDs in asymptomatic patients with predisposition to CD and demonstrated that anti-ID depletion from the serum restores a detectable humoral response against TG2. Our study provides an alternative approach to quantify CD-related autoantibodies in cases that would be defined "negative serology" with current diagnostic applications. Therefore, we suggest that developments of this technology could be designed for perspective routine tests.

Original languageEnglish
Pages (from-to)1079-1087
Number of pages9
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume202
Issue number4
DOIs
Publication statusPublished - Feb 15 2019

Keywords

  • Adolescent
  • Adult
  • Antibodies, Anti-Idiotypic/immunology
  • Autoantibodies/blood
  • Celiac Disease/genetics
  • Child
  • Child, Preschool
  • Female
  • GTP-Binding Proteins/immunology
  • Glutens/genetics
  • Humans
  • Immunoglobulin Idiotypes/immunology
  • Intestinal Mucosa/immunology
  • Intestines/immunology
  • Male
  • Middle Aged
  • Transglutaminases/immunology
  • Young Adult

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