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.
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 4day-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.
Immuno-Infectivology and Clinical Trials Research Area, Children's Hospital Bambino Gesù, Rome, Italy.
Valentina
V
Perri
Immuno-Infectivology and Clinical Trials Research Area, Children's Hospital Bambino Gesù, Rome, Italy.
Elena
E
Gianchecchi
Endocrine Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy.
Riccardo
R
Scarpa
Unit of Pediatrics, Department of Pediatric Sciences, University of Messina, Messina, Italy.
Mariella
M
Valenzise
Immunology Consultant, Rome, Italy.
Maria Manuela
MM
Rosado
Research Laboratories, Children's Hospital Bambino Gesù, Rome, Italy.
Ezio
E
Giorda
Endocrinology Department, Children's Hospital Bambino Gesù, Rome, Italy.
Antonino
A
Crinò
Endocrinology Department, Children's Hospital Bambino Gesù, Rome, Italy.
Marco
M
Cappa
Endocrine Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy.
Susi
S
Barollo
Endocrine Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy.
Silvia
S
Garelli
Endocrine Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy.
Corrado
C
Betterle
Immuno-Infectivology and Clinical Trials Research Area, Children's Hospital Bambino Gesù, Rome, Italy. Electronic address: alessandra.fierabracci@opbg.net.
Alessandra
A
Fierabracci
D056704:Adaptive Immunity; D000293:Adolescent; D000328:Adult; D000368:Aged; D000917:Antibody Formation / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015415:Biomarkers; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006706:Homeostasis; D006801:Humans; D007113:Immunity, Innate; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D016130:Immunophenotyping; D007223:Infant; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016884:Polyendocrinopathies, Autoimmune / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D000096927:AIRE Protein
D001323:Autoantibodies; D015415:Biomarkers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D051217:Toll-Like Receptor 9; D014157:Transcription Factors; D000096927:AIRE Protein
AIRE gene; Adaptive immunity; B cell phenotype; Innate immunity; Type 1 autoimmune polyglandular syndrome