Context. Type 1 autoimmune pancreatitis (AIP) represents the most frequent manifestation of IgG4 Related Disease (IgG4RD), a systemic fibro-inflammatory condition responsive to glucocorticoids (GC). Different B cell subpopulations have been implicated in IgG4RD-AIP pathogenesis but the effects of GC on these immune cells remain unknown. Objective. To describe the impact of GC on B cell subpopulations in patients with IgG4RD-AIP. Methods. 50 patients with active IgG4RD were studied. Flow cytometry was performed on peripheral blood in order to identify total B cells (CD19+CD20- and CD19+CD20+ cells), circulating plasmablasts (CD19+CD20-CD27+CD38++ cells), naïve B cells (CD19+CD20+CD27-CD38+ cells), memory B cells (CD19+CD20-CD27+CD38- cells), and circulating plasma cells (CD38+CD138+ cells). Disease activity was assessed by means of the IgG4RD responder index (IgG4RD RI). Flow cytometry was performed at baseline and after six months of immunosuppressive therapy with GC (0.6- 1mg/kg/day). 20 sex and age matched healthy subjects were used as controls (HC). Results. 28 patients (56% of our cohort) had IgG4RD-AIP. At baseline, circulating plasmablasts and plasma cells were expanded in IgG4RD patients (median 2815 and 200 cell/mL, respectively) compared to HC (p<0.05). Circulating plasma cells were not detected in HC. Total B cells and naïve B cells were reduced in IgG4RD patients compared to HC (p<0.05). No differences in memory B cells were observed (p >0.05). After six months of GC the median IgG4RD RI decreased from 9 to 2. Circulating plasmablasts, circulating plasma cells, and naïve B cells counts decreased in all patients together with disease improvement (p<0.05 compared to baseline). Total B cells and memory B cells were unaffected by GC. Conclusions. Clinical improvement induced by GC in patients with IgG4RD and IgG4RD-AIP correlates with depletion of circulating plasmablasts and plasma cells, and with reduction of naïve B cells counts. Our study provides evidence that circulating plasmablasts and plasma cells are linked to the pathogenesis of IgG4RD-AIP and can be used to monitor disease activity.
Effects Of Glucocorticoids On B Cell Subpopulations In Patients With IgG4-Related type I autoimmune pancreatitis
Marco Lanzillotta;DELLA TORRE E;Paolo Giorgio Arcidiacono;Stefano Crippa;Stefano Partelli;Massimo Falconi;Lorenzo Dagna.
2017-01-01
Abstract
Context. Type 1 autoimmune pancreatitis (AIP) represents the most frequent manifestation of IgG4 Related Disease (IgG4RD), a systemic fibro-inflammatory condition responsive to glucocorticoids (GC). Different B cell subpopulations have been implicated in IgG4RD-AIP pathogenesis but the effects of GC on these immune cells remain unknown. Objective. To describe the impact of GC on B cell subpopulations in patients with IgG4RD-AIP. Methods. 50 patients with active IgG4RD were studied. Flow cytometry was performed on peripheral blood in order to identify total B cells (CD19+CD20- and CD19+CD20+ cells), circulating plasmablasts (CD19+CD20-CD27+CD38++ cells), naïve B cells (CD19+CD20+CD27-CD38+ cells), memory B cells (CD19+CD20-CD27+CD38- cells), and circulating plasma cells (CD38+CD138+ cells). Disease activity was assessed by means of the IgG4RD responder index (IgG4RD RI). Flow cytometry was performed at baseline and after six months of immunosuppressive therapy with GC (0.6- 1mg/kg/day). 20 sex and age matched healthy subjects were used as controls (HC). Results. 28 patients (56% of our cohort) had IgG4RD-AIP. At baseline, circulating plasmablasts and plasma cells were expanded in IgG4RD patients (median 2815 and 200 cell/mL, respectively) compared to HC (p<0.05). Circulating plasma cells were not detected in HC. Total B cells and naïve B cells were reduced in IgG4RD patients compared to HC (p<0.05). No differences in memory B cells were observed (p >0.05). After six months of GC the median IgG4RD RI decreased from 9 to 2. Circulating plasmablasts, circulating plasma cells, and naïve B cells counts decreased in all patients together with disease improvement (p<0.05 compared to baseline). Total B cells and memory B cells were unaffected by GC. Conclusions. Clinical improvement induced by GC in patients with IgG4RD and IgG4RD-AIP correlates with depletion of circulating plasmablasts and plasma cells, and with reduction of naïve B cells counts. Our study provides evidence that circulating plasmablasts and plasma cells are linked to the pathogenesis of IgG4RD-AIP and can be used to monitor disease activity.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
