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