The following is an excerpt from the article, “Breaking Bad: IgG4 in Autoimmunity” from Science Trends.
IgG4: friend or foe?
ERIC M. MUKHERJEE & AIMEE S. PAYNE
Our laboratory researches a rare and debilitating autoantibody-mediated disease called pemphigus vulgaris, in which the immune system generates antibodies against desmogleins, which are proteins responsible for holding skin cells together. The result is painful, sometimes deadly, blistering of the skin and mucous membranes, requiring powerful immune suppressants such as steroids, mycophenolate, and the anti-B cell agent rituximab for disease control. Because pemphigus vulgaris has a well-characterized target, we study it as a model autoimmune disease to better understand why and how the immune system makes mistakes, so that we can develop better ways of reversing these mistakes and hence, better treat disease.
Patients with pemphigus vulgaris are known to have autoantibodies of the IgA1, IgA2, IgG1, and IgG4 subclasses, with IgG4, in particular, being a marker of active disease. As mentioned above, IgG4 is typically considered an anti-inflammatory antibody, induced during states of chronic immune stimulation to dampen disease.
Beekeepers and individuals undergoing allergic desensitization therapy develop IgG4 antibody responses that are thought to block symptoms caused by IgG1 or IgE reacting to the same stimuli, one of the reasons why people can outgrow an allergy from childhood. However, in pemphigus vulgaris, the antibody variable region is sufficient to disrupt skin cell adhesion and cause blisters, so trying to suppress these unruly variable regions with a law-abiding constant region can’t override this pathologic effect. Thus, although the immune system is trying all its usual tricks to stop the disease, the switch of B cells to the IgG4 subclass does not allow pemphigus vulgaris patients to outgrow or remit disease but instead becomes the defining immunologic feature of their disease.
Continue reading the full article on Science Trends.
This article was originally published in Science Trends on October 19, 2018.