Long-term effects of intensive B cell depletion therapy in severe cases of IgG4-related disease with renal involvement

Giacomo Quattrocchio,Michela Ferro,Carlo Massara,Dario Roccatello,Roberta Fenoglio,Antonella Barreca,Savino Sciascia,Giulio Del Vecchio,Andrea Demarchi,Cristiana Rollino

doi:10.1007/s12026-020-09163-3

Giacomo Quattrocchio, Michela Ferro + Show 8 more

Open Access

https://doi.org/10.1007/s12026-020-09163-3

Copy DOI

Abstract

IgG4-related disease (IgG4-RD) is an immune-mediated disorder often showing elevated serum IgG4 concentrations, dense T and B lymphocyte infiltration, and IgG4-positive plasma cells and storiform fibrosis. We prospectively evaluated for 4 years 5 patients with histologically proven IgG4-RD of whom 3 had tubulointerstitial nephritis (TIN) and 2 had retroperitoneal fibrosis (RPF). They received an intensive B depletion therapy with rituximab. The estimated glomerular filtration rate of TIN patients after 1 year increased from 9 to 24 ml/min per 1.73 m2. IgG/IgG4 dropped from 3236/665 to 706/51 mg/dl, C3/C4 went up from 49/6 to 99/27 mg/dl, and the IgG4-RD responder index fell from 10 to 1. CD20+ B cells decreased from 8.7 to 0.5%. A striking drop in interstitial plasma cell infiltrate as well as normalization of IgG4/IgG-positive plasma cells was observed at repeat biopsy. Both clinical and immunological improvement persisted over a 4-year follow-up. Treating these patients who were affected by aggressive IgG4-RD with renal involvement in an effort to induce a prolonged B cells depletion with IgG4 and cytokine production decrease resulted in a considerable rise in eGFR, with IgG4-RD RI normalization and a noteworthy improvement in clinical and histological features. Furthermore, the TIN subgroup was shown not to need for any maintenance therapy.

Highlights

Often times, IgG4-related disease (IgG4-RD) is a heterogeneous disorder, whose features may include different organ involvement, high IgG4 concentration in the serum, and unusual histological findings
Whole blood samples collected in EDTA were stained with monoclonal antibodies against CD45 (APC 100 eBioscience Bender Medsystems, CA, USA), CD3 (FITC eBioscience Bender Medsystems, CA, USA), CD4 (PC7 Beckman Coulter, CA, USA), CD19 (Pacific BlueTM, Beckman Coulter, CA, USA), CD20 (PE Beckman Coulter, CA, USA), CD25 (PerCP-eFluor 710 eBioscience/Bender Medsystems, CA, USA), and FOXP3 (PE Staining set, eBioscience Bender Medsystems, CA, USA)
Histological confirmation was acquired by open biopsy of the mass lesion in patient N.4 and by surgical hysteroannessiectomy in patient N.5

Summary

Introduction

IgG4-related disease (IgG4-RD) is a heterogeneous disorder, whose features may include different organ involvement, high IgG4 concentration in the serum, and unusual histological findings. The latest include IgG4+ plasma-cell-enriched dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis [1, 2]. Men in their 50s and above are most often affected and generally display non-severe clinical presentation, potentially. Most common laboratory features are high serum concentration of IgG4 levels (observed in 50–70% cases) (> 135 mg/ dl) often associated with hypergammaglobulinemia (80–90% of cases). Almost half of the patients present with high serum IgE levels, peripheral eosinophilia, and hypocomplementemia. Less frequently antinuclear antibodies and rheumatoid factor can be observed [4,5,6]

Objectives

Methods

Results

Conclusion