title: Treatment of IgG4-related disease : Current and future approaches.
abstract: IgG4-related disease (IgG4-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 not 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 is 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 of the next few years.
authors.affiliation: Division of Rheumatology, Allergy, & Immunology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Perugino
authors.affiliation: Harvard Medical School; The Edward Fox Chair in Medicine, Massachusetts General Hospital, Boston, MA, USA. jhstone@mgh.harvard.edu.|Rheumatology Clinic/Yawkey 2, Massachusetts General Hospital, 55 Fruit Street, 02114, Boston, MA, USA. jhstone@mgh.harvard.edu.
authors.forename: J H
authors.initials: JH
authors.lastname: Stone
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy*; D019317:Evidence-Based Medicine; D005544:Forecasting; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods* / Q000639:trends*; D058990:Molecular Targeted Therapy / Q000639:trends*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D005938:Glucocorticoids; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents
keywords: Adverse effects; Antirheumatic agents; B-cells; Glucocorticoids; Monoclonal antibodies