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Where head the IgG4 related disease is a rare chronic fiber inflammatory disease that can affect almost any
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organ. while the mechanism of disease is not fully
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understood let's dive into the processes believed to under IgG4 related disease
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specifically how the immune system is taught to lead to inflammation and fibrosis that can
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result in repeated disease flares and organ damage for patients.
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awareness of how organ damage manifests is critical important to inform the timely
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diagnosis of IgG4 related disease.
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Let's start by looking at an example of an affected organ in IgG4 related disease where we
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can clearly observe some of the characteristic pathologic features of Tish inflammation and
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fibrosis. Here we can see a patient with IgG4 related
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disease affecting the lacrymal gland.
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Ttaining reveals Siform fibrosis, which resembles a basket wave appearance.
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Although specific features can vary based on the organ affected story from fibrosis is one
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of the key histopathologic findings in this disease.
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Another key finding in affected tissues is a dense lymphoplasmocytic infiltrate of B cells,
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including If positive plasma cells and T cells.
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Now let's review the different types of B cells that are believed to be a driver of I4 related
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disease pathogenesis.
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This Schematics shows how B cells mature from stell cells on the left all the way to antibody
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secreting Plasma blasts and plasma cells on the right.
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As shown here the CD 19 transmembrane protein is expressed on pro B cells in the early stages
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and continues to be expressed throughout the B cell lineage.
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CD 19 is expressed on both Plasmablasts and some plasma cells that produce IgG4.
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As you can see in this figure cd 19 is expressed on a wider range of maturing B cells
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compared to cd 20 expression CD 19 positive B cells are believed to be drivers of T
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inflammation and fibrosis in IgG4 related disease through multiple mechanisms here you
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can see how B cells are thought to drive disease pathophysiology through their
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interaction with T cells.
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specifically cd 19 positive and cd 20 positive B cells bind to T cells which differentiate
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into cytotoxic D lymphocytes that secrete cytokines and chemokines promoting inflammation
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and fibrosis. Additionally, as B cells mature into cd 19
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expressing Plasma blasts and plasma cells they begin to secrete IgG4 antibodies.
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in Patients with IgG4 related disease Plasma Blas populations are expanded resulting in
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increased circulating Plasma blasts and Serum If that is frequently observed in active
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disease, although the exact role of IgG4 remains an area of investigation.
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B Cells are also known to produce proinflammatory and collagenous proteins that
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contribute to inflammation and fibrosis.
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Clinical studies also support the role of CD 19 positive B cells,
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including Plasmablasts as drivers of IgG4 related disease Activity.
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CD 19 is expressed on the surface of B cells as the maturing to antibody secreting Plasma
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blasts and certain plasma cells that are believed to be a driver of pathogenesis.
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in untreated patients increasing CD9 Positive Plasma blasts and plasma cells correlated with
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greater number of organs affected, higher serumide gf levels and more severe disease when
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patients were treated with anti-cd 20 B cell depleting therapy CD9 positive Plasma blasts
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levels decline during remission.
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levels rose in patients who relapsed following B cell depletion together These clinical
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studies suggest that sentin positive Plasma blasts and plasma cells may be an important
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biomarker of disease activity and key players in inflammation and fibrosis observe the
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IgG4 related disease. fibrosis is often associated with functional
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and structural organ damage at affected sites in summary today we learned about immune
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mediated processes believed to under IgG4 related disease and touched on the following key points
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IgG4 related disease is characterized by a tissue infiltrate of IgG4 positive B cells and Cd
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positive T cells, which may lead to inflammation tumor lesions and tissue fibrosis.
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CD 19 is expressed on the surface of B cells dem maturing to antibody secreting Plasma blasts CD
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nineteen positive B cells are believed to be drivers of inflammation and fibrosis in
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patients with IgG4 related disease Disease activity correlates with CD 19 positive Plasma
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blasts and Plasma cells suggesting that CD9 positive B cells may be an important biomarker
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of disease activity and a key player in IgG4 related disease.
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Thanks for listening please see the other videos in this series from my colleagues for
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more information on IgG4- related disease, including disease overview,
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the importance of a multidisciplinary approach and strategies for proactive Management.