An Immune Disease Easily Mistaken for Cancer: Why These Drugs Are Used for IgG4-Related Disease

IgG4-related disease (IgG4-RD) is a systemic immune-mediated disorder characterized by chronic inflammation and progressive fibrosis. Since the disease was systematically defined, its clinical spectrum has expanded continuously. It is now known to affect multiple organs, including the pancreas, biliary tract, lacrimal glands, salivary glands, kidneys, lungs, retroperitoneum, and central nervous system.

Diagnosing IgG4-RD remains clinically challenging. On imaging, IgG4-RD typically presents with:

● Diffuse organ enlargement

● Nodular or mass-like lesions

● Tissue thickening, encasing vessels or ducts

As a result, it is easily confused with malignant tumors, infectious diseases, or other autoimmune disorders. Many patients undergo repeated investigations and even unnecessary invasive procedures before a correct diagnosis is made.

Through continuous tracking of drugs and clinical data in immune-mediated diseases, DengYue Medicine has observed that the key reason for frequent misdiagnosis is straightforward:IgG4-RD looks like a tumor externally, but its underlying mechanism is immune dysregulation.

From IgG4 Antibodies to B Cells: The Evolution of Pathogenesis

Although the disease name includes “IgG4,” current research widely agrees that IgG4 antibodies are not the initiating cause of the disease, but rather a marker of immune dysregulation.

Key immunological features of IgG4-RD include:

● Abnormal activation and expansion of B cells

● Massive infiltration of IgG4-positive plasma cells in affected tissues

● Accompanying T-cell involvement and activation of pro-fibrotic signaling

In this process, B cells are not merely the source of IgG4 antibodies. They also help maintain the inflammatory microenvironment and promote fibrosis through antigen presentation and cytokine secretion.

Based on this understanding, the therapeutic strategy for IgG4-RD has gradually shifted from simply suppressing inflammation to directly targeting B-cell-related immune pathways.

Rituximab: A Mature B-Cell Depletion Strategy Targeting CD20

Rituximab is a monoclonal antibody directed against CD20, a molecule expressed mainly on mature B cells, but not on hematopoietic stem cells or terminally differentiated plasma cells.

This target profile defines its mechanism of action:

● Effectively depletes mature B cells in the peripheral blood and tissues

● Blocks further differentiation into plasma cells

● Indirectly reduces sustained production of IgG4 antibodies

In IgG4-RD, multiple studies and real-world experience have shown that rituximab can:

● Improve organ enlargement and imaging abnormalities

● Reduce serum IgG4 levels

● Steroid-sparing effect and lower relapse risk

Therefore, rituximab is widely recognized as a valuable treatment option for patients with an inadequate response to steroids or recurrent disease.

Inebilizumab: A Broader B-Cell Intervention Targeting CD19

Inebilizumab targets CD19, a molecule expressed throughout multiple stages of B-cell development, including precursor B cells, mature B cells, and some plasma cells.

Compared with CD20, targeting CD19 offers potential advantages:

● Acts at an earlier stage of B-cell development

● Covers a wider range of B-cell subsets

● Theoretically enables deeper suppression of antibody production

Due to this mechanism, inebilizumab holds significant research value in antibody-mediated immune diseases.Currently, its approved indications are mainly in immune-mediated neurological disorders, and its use in IgG4-RD remains investigational, with relatively limited clinical data.

Thus, its role in IgG4-RD is best understood as a promising mechanism-based therapeutic direction, rather than an established standard of care.

Conclusion

IgG4-related disease is evolving from a “rare, often misdiagnosed condition” into a disease model with relatively clear immune mechanisms and increasingly refined treatment strategies.

The B-cell-targeted therapeutic approach not only provides new treatment options for patients but also serves as an important model for understanding chronic immune-mediated diseases.With ongoing research, therapeutic strategies targeting different pathways will further enrich the management of IgG4-RD.