B Cells in IgG4-RD Pathogenesis and Setting Treatment Goals

In "B Cells in IgG4-RD Pathogenesis and Setting Treatment Goals," the panel connects disease biology to the practical aims of therapy.

Dr. Della Torre begins with what remains unknown. Researchers do not know why the disease mainly affects older men or why it targets the salivary glands in some patients and the retroperitoneum in others. They also do not know why most patients relapse while a few enter spontaneous remission. What is clear, he says, is the central role of B lymphocytes. B-cell depletion improves the disease regardless of the organ involved. When started promptly, mass-forming lesions nearly disappear.

It remains uncertain whether autoantibodies drive the disease, as in classic autoimmune conditions. Dr. Della Torre suggests that B cells likely activate pathogenic T lymphocytes. Together, these cells drive fibrosis of affected tissues, the ultimate outcome of disease pathogenesis.

Dr. Katz then outlines treatment goals. The first is improving symptoms caused by active disease. He reminds patients that some symptoms may reflect damage rather than activity, so remission may not eliminate every symptom. The second goal is preventing damage. Even asymptomatic inflammation of the pancreas, kidneys, orbits, or retroperitoneum can cause substantial damage, so he treats it.

Goals vary by organ, Dr. Katz explains. In asymptomatic salivary gland enlargement, the worst likely outcome is dry mouth. Whether untreated disease increases that risk has never been studied, though it seems plausible. He discusses the risks of dry mouth and the risks of treatment. After that conversation, some patients choose monitoring instead.

He discusses the possibility of future organ involvement with every patient. He images the chest, abdomen, and pelvis before labeling disease as isolated glandular involvement. When serum IgG4 is highly elevated but only gland disease is visible, he warns that internal inflammation may be undetectable on imaging. He monitors those patients closely. Prominent serology may push him toward treatment to control hidden disease.

In "Individualizing IgG4-RD Treatment Around Comorbidities and Limited Options," Dr. Della Torre will explain why drug availability, more than patient factors, often dictates treatment choice.