Background IgG4-Related Disease (IgG4-RD) is a systemic fibro-inflammatory condition characterized by oligoclonal expansion of IgG4+ class-switched plasmablasts (PBs) (1). PBs swiftly decline together with clinical improvement after rituximab, suggesting a role for B cells in the pathogenesis of IgG4-RD (2). Studies with alternative effective non B-cell depleting therapies (3) are needed in order to confirm the pathogenic importance of PBs and their utility as disease biomarkers.
Objectives To assess the impact of combined therapy with prednisone (PDN) and methotrexate (MTX) on B cell subpopulations in patients with IgG4-RD.
Methods Five patients with active biopsy proven IgG4-RD were treated with PDN (0.6–1 mg/kg) and MTX (10–20 mg per week). PDN was gradually tapered and withdrawn in 6 months. Disease activity, partial (PR) and complete response (CR) were assessed through the IgG4-RD Responder Index (IgG4-RD RI) (4). Serological, immunological and radiological studies were performed according to the clinical presentation. Flow cytometry was used to measure PBs (CD19+CD20-CD27+CD38+bright cells), naïve (CD19+CD20+CD27-CD38+ cells), and memory (CD19+CD20+CD27+CD38- cells) B cells at baseline, after 3 and 6 months of therapy. Nine age and sex matched subjects were used as healthy controls (HC).
Results At disease onset, the median IgG4-RD RI was 9 (normal <3). The median serum IgG4 level was 534 mg/dl (normal <135mg/dL). Circulating PBs were increased (median 7000 cells/mL) compared to HC (median 605 cells/mL; p<0.004). PBs showed a positive correlation with the number of organs involved (r=0.77), with serum IgG4 level (r=0.87), and with disease activity (r=0.73). The number of circulating memory B cells was comparable between IgG4-RD patients and HC (p=0.57). Naïve B cells were significantly lower in IgG4-RD patients compared to HC (p<0.05). After 6 months of therapy 4 patients achieved CR (IgG4-RD RI <3) and 1 PR. Serum IgG4 level decreased in all patients but normalized only in one patient at 6 months. Circulating PBs declined to levels comparable to HC (median 230 cells/mL, p=0.3). Memory B cells were unaffected by the therapy, while naïve B cells showed a declining trend, yet not statistically significant compared to baseline levels (p>0.05)
Conclusions PBs and naïve B cells are expanded and reduced, respectively, in patients with active IgG4-RD compared to HC. Combined therapy with PDN and MTX leads to clinical improvement and to normalization of circulating PBs. Naïve B cells slightly decrease, while memory B cells are not affected by immunosuppressive treatment
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Disclosure of Interest None declared