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The Immunologic Paradoxes of IgG4-Related Disease

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Abstract

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.

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Funding

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).

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Shanghai JiaoTong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China

    Xiao Xiao, Min Lian & Xiong Ma

  2. Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai JiaoTong University; Shanghai JiaoTong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China

    Xiao Xiao, Min Lian & Xiong Ma

  3. State Key Laboratory for Oncogenes and Related Genes, Shanghai JiaoTong University; Shanghai JiaoTong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China

    Xiao Xiao, Min Lian & Xiong Ma

  4. Renji Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China

    Xiao Xiao, Min Lian & Xiong Ma

  5. Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, 451 Health Sciences Drive, Suite 6510, Davis, CA, 95616, USA

    Weici Zhang & M. Eric Gershwin

Authors
  1. Xiao Xiao
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  2. Min Lian
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  3. Weici Zhang
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  4. M. Eric Gershwin
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  5. Xiong Ma
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Corresponding authors

Correspondence to M. Eric Gershwin or Xiong Ma.

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Xiao Xiao and Min Lian share co-first authorship.

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Xiao, X., Lian, M., Zhang, W. et al. The Immunologic Paradoxes of IgG4-Related Disease. Clinic Rev Allerg Immunol 54, 344–351 (2018). https://doi.org/10.1007/s12016-018-8679-y

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  • DOI: https://doi.org/10.1007/s12016-018-8679-y

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