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International Journal of Rheumatology
Volume 2012, Article ID 789164, 6 pages
Review Article

IgG4-Related Fibrotic Diseases from an Immunological Perspective: Regulators out of Control?

1Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, 1066 CX Amestrdam, The Netherlands
2Sanquin Blood Supply Foundation, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands

Received 30 December 2011; Accepted 14 April 2012

Academic Editor: Yoh Zen

Copyright © 2012 Laura C. Lighaam et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Patients with autoimmune pancreatitis have a striking polyclonal elevation of total IgG4 in serum. This observation has been confirmed and extended to other fibrotic conditions (that are therefore called IgG4-related disease) but as yet remains unexplained. The affected tissue contains many IgG4-producing plasma cells embedded in a fibrotic matrix originating from activated mesenchymal (stellate) cells. We propose that the process results from an unusual interaction between two regulatory systems: the regulatory arm of the immune system (including Bregs) and the tissue repair regulatory components orchestrated by the activated stellate cell. This interaction results in ongoing mutual activation, generating TGFbeta, IL10, and vitamin D. This environment suppresses most immune reactions but stimulates the development of IgG4-producing plasma cells.