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

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• 作者：Valentina Perri^a ; Elena Gianchecchi^a ; ¹ ; Riccardo Scarpa^b ; Mariella Valenzise^c ; Maria Manuela Rosado^d ; Ezio Giorda^e ; Antonino Crinò ; ^f ; Marco Cappa^f ; Susi Barollo^b ; Silvia Garelli^b ; Corrado Betterle^b ; Alessandra Fierabracci ; MD PhD^a ; ^{alessandra.fierabracci@opbg.net}
• 关键词：A ; alopecia ; AD ; Addison&rsquo ; s disease ; AG ; atrophic gastritis ; AIH ; autoimmune hepatitis ; ATD ; autoimmune thyroid disease ; CDI ; central diabetes insipidus ; CDP ; chronic demyelinating polyneuropathy ; CMC ; chronic mucocutaneous candidiasis ; Co ; constipation ; E ; epilepsy ; EH ; enamel hypoplasia ; GCA ; autoimmune chronic gastritis ; HC ; hypercholesterolemia ; HP ; hypoparathyroidism ; ID ; intestinal dysfunction ; K ; keratoconjunctivitis ; MLS ; malabsorption ; ND ; nail dystrophy ; O ; obesity ; OM ; ocular mya
• 刊名：Immunobiology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：222
• 期：2
• 页码：372-383
• 全文大小：1886 K
• 卷排序：222

文摘

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.