Altered B cell homeostasis and Toll-like receptor 9-driven response in patients affected by autoimmune polyglandular syndrome Type 1. Altered B cell phenotype and dysregulation of the B cell function in APECED patients

Valentina Perri, Elena Gianchecchi, Riccardo Scarpa, Mariella Valenzise, Maria Manuela Rosado, Ezio Giorda, Antonino Crinò, Marco Cappa, Susi Barollo, Silvia Garelli, Corrado Betterle, Alessandra Fierabracci

Research output: Contribution to journalArticle

Abstract

APECED is a T-cell mediated disease with increased frequencies of CD8+ effector and reduction of FoxP3+ T regulatory cells. Antibodies against affected organs and neutralizing to cytokines are found in the peripheral blood. The contribution of B cells to multiorgan autoimmunity in . Aire-/- mice was reported opening perspectives on the utility of anti-B cell therapy.We aimed to analyse the B cell phenotype of APECED patients compared to age-matched controls. FACS analysis was conducted on PBMC in basal conditions and following CpG stimulation. Total B and switched memory (SM) B cells were reduced while IgM memory were increased in patients. In those having more than 15 years from the first clinical manifestation the defect included also mature and transitional B cells; total memory B cells were increased, while SM were unaffected. In patients with shorter disease duration, total B cells were unaltered while SM and IgM memory behaved as in the total group. A defective B cell proliferation was detected after 4. day-stimulation. In conclusion APECED patients show, in addition to a significant alteration of the B cell phenotype, a dysregulation of the B cell function involving peripheral innate immune mechanisms particularly those with longer disease duration.

Original languageEnglish
JournalImmunobiology
DOIs
Publication statusAccepted/In press - May 26 2016

Keywords

  • Adaptive immunity
  • AIRE gene
  • B cell phenotype
  • Innate immunity
  • Type 1 autoimmune polyglandular syndrome

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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