Today in CTU rounds we discussed
the case of a 72-year-old woman, originally born in Egypt, with idiopathic
cholangitis. Lot’s of interesting
questions and stimulating discussion took place! IM gave a great
presentation on IgG4-related disease (IgG4RD). Here is a brief overview of IgG4
and an attempt to answer a few of the tough questions that came up in our
discussions:
New England Journal of Medicine review
article on IgG4-related disease (2012)
Highlights:
1.
IgG4-related disease has been described in the biliary
tree, salivary glands, periorbital tissues, kidneys, lungs, lymph nodes,
meninges, aorta, breast, prostate, thyroid, pericardium, and skin.
2.
For pathological findings, diagnostic criteria and
treatment- please see the review article above.
3.
IgG4 has negligible binding to C1q and Fcγ receptors. In theory, IgG4 does not activate the classical complement
pathway effectively and has been traditionally considered to play only a limited role in immune activation.
IgG4 does not have the ability to form immune complexes. It’s production is
controlled mostly by Th2 cells. REPEATED antigen stimulation activates IgG4.
4.
“…the excess of IgG4 may simply be an overexpression of
these antibodies in response to an unknown primary inflammatory stimulus…”
5.
IgG4 plays a
major role in other diseases:
pemphigous vulgaris, idiopathic membranous glomerulonephritis and thrombotic
thrombocytopenic purpura (it is the autoantibody against ADAMTS13).
6.
Fevers and elevations of C-reactive protein levels are
unusual in IgG4RD. The disorder is often identified incidentally through radiologic findings or unexpectedly in
pathological specimens.
7.
Two common findings in IgG4-related disease can cause
tumour-like swellings in many organ systems and is often associated with allergic
disease.
a.
Many patients with IgG4-related disease have allergic
features such as atopy, eczema, asthma, and modest peripheral-blood
eosinophilia.
b.
Up to 40% of patients with IgG4-related disease have
allergic diseases such as bronchial asthma or chronic sinusitis.
8.
30% of
patients with IgG4-related disease on pathological biopsy have normal serum
IgG4 levels. IgG4 doesn’t always decrease
with steroid treatment even when the patient improves clinically.
How good is the positive predictive value of
an elevated IgG4 level? Can the test characteristics be improved by examining
the IgG4 to IgG ratio?
According to
an article in the Annals of the Rheumatic diseases the PPV is only 34% and the test characteristics are not improved when
you examine the IgG4 to IgG ratio. Doubling the cut-off improved the
specificity of the test from 60 to 91% but at a great cost to the sensitivity.
That being said- some investigators have previously reported that an elevated
ratio can be helpful in distinguishing IgG4RD from other diseases with
associated elevations of IgG4.
Today we also learned that elevated IgG4 levels
(along with IgE) are associated with parasitic infections such as filariasis,
schistosomiasis and stongyloides!
If you’re really
curious about IgG4 you might be interested in this appropriately titled
article: Immunoglobulin G4: An Odd Antibody
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