Pathophysiology-Based Approaches to Treatment
IgG4-related disease (IgG-RD) is capable of causing great morbidity and even mortality if the condition remains undiagnosed or poorly treated yet is typically a treatment-responsive disorder. Glucocorticoids have not been studied rigorously, and practices with regard to dosing and duration of treatment remain largely empiric. In addition, IgG4-RD patients are often particularly susceptible to and intolerant of the deleterious effects of glucocorticoid therapy. B cell depletion with anti-CD20 monoclonal antibodies appears to be a rapid, effective means of obtaining disease control and limiting patients’ glucocorticoid exposure, but this option is frequently available. Other therapies targeting the B cell lineage may also be efficacious, and one is under study. The means by which depletion or inhibition of B cells and their progeny ameliorate IgG4-RD are coming into focus now through careful mechanistic studies of samples from treated patients.
The mechanistic understanding of IgG4-RD will bring an array of specific targets for therapeutic intervention. Plasmablast-directed therapy with a CD19 monoclonal antibody is currently in clinical trials. CD4+ cytotoxic T lymphocytes and fibrosis, both observed nearly universally in the tissue of IgG4-RD patients, present two unexploited vulnerabilities in controlling and even reversing the effects of the disease. Further development of such therapies is a major goal for the next few years.
- 9.Masaki Y for the All-Japan IgG4-RD Team; abstract presentation at the 2014 Second International Symposium on IgG4-Related Disease and Associated Conditions.Google Scholar