Re: Fc Receptor Expression - What does it mean?

[Guest guest]

OK, so here comes a mini-lesson in molecular immunology! You might like

to draw this out as I describe it so it will be easier to understand.

Each antibody molecule is Y-shaped. The V part of the Y is the ab

fragment (Fab) and the straight stem of the Y is the c fragment (Fc).

The Fab carries the specificity allowing the antibody molecule to bind

to an antigen (which can be an allergen in the case of IgE) but the Fc

does not. IgE's Fc is the region that binds to the mast cell, thereby

triggering histamine release from the mast cell and getting the

allergic cascade started. Both the Fab and the Fc also have regions

specific to the class of antibody (IgG or IgE or others).

Xolair recognizes and binds only to IgE's Fc, so that the IgE can no

longer bind to mast cells, thus preventing the release of histamine and

starting the allergic cascade. The mast cell's binding site for IgE's

Fc is called the Fc receptor and is " expressed " (exposed) on the

external surface of the membrane enclosing the cell. The precursors to

mast cells are called basophils and they also have Fc receptors for

IgE. Interestingly, and this may be what you saw in the report about

Xolair, the expression (presence) of the Fc receptors on basophils are

decreased in the presence of Xolair.

This is the basis for the theory that Xolair might lessen allergic

immune responses by a separate mechanism in addition to simply directly

inactivating IgE. The thinking is that since the basophils' Fc receptor

expression is lowered by Xolair, perhaps the mast cells that develop

from those basophils might also have decreased Fc receptor expression

so that besides Xolair binding up and inactivating IgE, Xolair

treatment might also decrease the number of Fc receptors on mast cells.

That reduction in Fc receptors would be expected to reduce the chances

that any intact IgE could bind to mast cells.

I hope that's clear - please let me know if it's not so I can try to

explain it better.

Fran

--- In , " instdesgn1 " <instdesgn1@...>

wrote:

>

> Reading an FDA report about Xolair I came across something about " Fc

> Receptor Expression. " It seems to be somehow associated with IgG

which

> I thought had something to do with immunity but don't remember for

> sure. Does anyone know the significance of this term in the report?

>

> Thx

>

[Guest guest]

wow, thanks for that in-depth description - sounds great to me!

> >

> > Reading an FDA report about Xolair I came across something

about " Fc

> > Receptor Expression. " It seems to be somehow associated with

IgG

> which

> > I thought had something to do with immunity but don't remember

for

> > sure. Does anyone know the significance of this term in the

report?

> >

> > Thx

> >

>

[Guest guest]

Fran, I have read somewhere that there is some thinking in the Xolair

establishment that Xolair may have anti-inflammatory properties. I

have thought that the decrease in inflammation is simply a result of

the decrease in allergic cascade activity due to Xolair preventing IgE

from binding to the mast cell. If there is also a decrease in Fc

receptor expression on the mast cell, might that also attribute to a

decrease in inflammation?

Just trying to wrap my brain around science, a difficult thing for an

English major.

Thanks so much for the clear way you explain things to all of us lay

people. I'm sure you are happy to be retired, but I am sure children

and families are missing your services!

Addy

> >

> > Reading an FDA report about Xolair I came across something about " Fc

> > Receptor Expression. " It seems to be somehow associated with IgG

> which

> > I thought had something to do with immunity but don't remember for

> > sure. Does anyone know the significance of this term in the report?

> >

> > Thx

> >

>

[Guest guest]

Yes, as far as I know the thinking about reduction of inflammation is

based on the information about the decrease in Fc receptors.

Histamine realease causes enough problems on its own but also

triggers other immune events that worsen the inflammation.

Thanks for your kind comments. Actually, I'm disabled rather than

retired, due to multiple medical problems including asthma and

chronic fatigue, and I'm very sad about no longer being in practice.

I really miss my kids and families. I do some volunteer work with

medically indigent kids and grieving kids and that does help a bit

but there's a big hole in my heart where my patients used to be.

Fran

> > >

> > > Reading an FDA report about Xolair I came across something

about " Fc

> > > Receptor Expression. " It seems to be somehow associated with

IgG

> > which

> > > I thought had something to do with immunity but don't remember

for

> > > sure. Does anyone know the significance of this term in the

report?

> > >

> > > Thx

> > >

> >

>