Clinical Reviews in Allergy & Immunology

, Volume 54, Issue 2, pp 344–351 | Cite as

The Immunologic Paradoxes of IgG4-Related Disease

  • Xiao Xiao
  • Min Lian
  • Weici Zhang
  • M. Eric GershwinEmail author
  • Xiong MaEmail author


IgG4-related disease (IgG4-RD), which usually occurs in middle-aged and elderly men, is a newly recognized fibroinflammatory condition characterized by swelling and sclerosis of involved organs, increased IgG4-positive plasma cell infiltration in lesions, and elevated IgG4 concentration in serum. Despite growing interest in the research, the pathophysiological mechanism remains elusive. Most IgG4-RD patients respond well to steroid therapy initially, but recurrent and refractory cases are common, especially in advanced fibrotic stage. Recent studies have documented the heterogeneity of the B cell lineages, which suggests their multiple functions in IgG4-RD beyond IgG4 production, such as cytokine secretion, antigen presentation, autoantibody production, and modulation of T and B cell interactions. Thus, a critical balance exists between pathogenic and regulatory B subsets to prevent immunopathology. A prompt response to B cell depletion therapy reported in recent cases strongly suggests the imbalance within B cell lineages in IgG4-RD. A more precise understanding of the pathogenesis of IgG4-RD will open up new perspectives for therapeutic strategy. With a particular emphasis on the novel B cell-targeted therapeutic strategies, this review highlights the immunologic features of IgG4-RD and the possible roles of B cell lineages in the pathogenesis of IgG4-RD.


IgG4 IgG4-related disease B cells Plasmablasts Rituximab 


Funding Information

This work was supported by the National Natural Science Foundation of China (81620108002 to Xiong Ma, 81500435 to Xiao Xiao) and Shanghai Yangfan Program (15YF1407100 to Xiao Xiao).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Authors and Affiliations

  1. 1.Division of Gastroenterology and HepatologyShanghai JiaoTong University, Shanghai Institute of Digestive DiseaseShanghaiChina
  2. 2.Key Laboratory of Gastroenterology and Hepatology, Ministry of HealthShanghai JiaoTong University; Shanghai JiaoTong University, Shanghai Institute of Digestive DiseaseShanghaiChina
  3. 3.State Key Laboratory for Oncogenes and Related GenesShanghai JiaoTong University; Shanghai JiaoTong University, Shanghai Institute of Digestive DiseaseShanghaiChina
  4. 4.Renji Hospital, School of MedicineShanghai JiaoTong University, Shanghai Institute of Digestive DiseaseShanghaiChina
  5. 5.Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical ImmunologyUniversity of California at Davis School of MedicineDavisUSA

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