Article Text

Download PDFPDF

THU0538 Effects of glucocorticoids and methotrexate-based therapeutic regimens on b cell subpopulations in patients with igg4-related disease
  1. M Lanzillotta1,
  2. E Della Torre1,
  3. R Milani2,
  4. E Bozzalla1,
  5. L Rovati1,
  6. E Bozzolo1,
  7. M Falconi3,4,
  8. L Dagna1,4
  1. 1Internal Medicine, Allergy and Clinical Immunology
  2. 2Unit of Immuno-hematology and Bone Marrow Transplant
  3. 3Pancreatic Surgery Unit, San raffaele Scientific Institute
  4. 4Università Vita-Salute San Raffaele, Milan, Italy


Background IgG4-related disease (IgG4-RD) is a systemic fibro- inflammatory disorder characterized by fibrotic lesions infiltrated by IgG4 positive plasma cells (1). The prompt clinical responses obtained after B cell depletion with rituximab in IgG4-RD patients suggest that B lymphocytes drive the pathogenesis of this condition and sustain disease activity (2). This conclusion, however, requires further confirmation because IgG4-RD responds also to non-B cell depleting therapies such as glucocorticoids and methotrexate

Objectives To evaluate the effects of glucocorticoids and methotrexate-based therapeutic regimens on B lymphocyte subpopulations in patients with IgG4-RD.

Methods Sixteen patients with active IgG4-RD were studied. FACS analysis was performed on peripheral blood in order to identify the following B cell subpopulations: 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), circulating plasma cells (CD38+CD138+ cells). Disease activity was assessed by means of the IgG4-RD responder index (IgG4-RD RI). Flow cytometry was performed at baseline and after six months of immunosuppressive therapy with glucocorticoids (0.6–1mg/kg/day) and/or methotrexate (10–20mg/week). 16 sex and age matched healthy subjects were used as controls.

Results At baseline, circulating plasmablasts were expanded in IgG4-RD patients (median 3780 cell/mL; range 330–9300) compared to controls (median 280 cell/mL; range 0–1000) (p<0.05); total B cells (median 133000 cell/mL; range 34000–569000) and naïve B cells (median 13080 cell/mL; range 1970–64270) were reduced in IgG4-RD patients compared to controls (median 280 cell/mL; range 194–330; and median 54020 cell/mL; range 21050–106780, respectively) (p<0.05). No circulating plasma cells were detected in healthy controls. No differences in memory B cells were observed (p>0.05). Circulating plasmablasts but not other B cell subsets positively correlated with serum IgG4 levels, number of organ involved, and IgG4-RD RI (p<0.05). At six months follow-up, the median IgG4-RD 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=0.0002, 0.0002 and 0.025 compared to baseline values, respectively); total B cells and memory B cells were unaffected by immunosuppressive therapy.

Conclusions Non-B cell depleting therapies based on glucocorticoids and/or methotrexate induce clinical improvement and deplete circulating plasmablasts, plasma cells and naïve B cells in patients with IgG4-RD; circulating total B cells and memory B cells are not affected by glucocorticoids and methotrexate. Our study, performed with non-B cell depleting agents, provides clinical evidences that circulating plasmablasts are likely linked to IgG4-RD pathogenesis and disease activity.


  1. Della Torre E, Lanzillotta M, Doglioni C. Immunology of IgG4-related disease. Clin Exp Immunol. 2015.

  2. Wallace ZS, Mattoo H, Carruthers M, et al. Plasmablast as a biomarker of IgG4-related disease, independent of serum IgG4 concentrations. 2014.


Disclosure of Interest None declared

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.