Pathophysiology-Based Approaches to Treatment

  • Cory A. Perugino
  • John H. StoneEmail author


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.


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© Springer Science+Business Media Singapore 2019

Authors and Affiliations

  1. 1.Division of Rheumatology, Allergy, and ImmunologyMassachusetts General HospitalBostonUSA
  2. 2.Department of MedicineHarvard Medical SchoolBostonUSA
  3. 3.Rheumatology ClinicMassachusetts General HospitalBostonUSA

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