The Immunologic Paradoxes of IgG4-Related Disease

Xiao Xiao, Min Lian, Weici Zhang, M. Eric Gershwin, Xiong Ma

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalClinical Reviews in Allergy and Immunology
StateAccepted/In press - Feb 19 2018


  • B cells
  • IgG4
  • IgG4-related disease
  • Plasmablasts
  • Rituximab

ASJC Scopus subject areas

  • Immunology and Allergy


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