Q:

11/16/2011
In your opinion which is better: the CU index from IBT which measures histamine release from donor basophils or the CU index from National Jewish which measures CD203c upregulation when evaluating for Autoimmune Chronic Urticaira? Are there any other tests which are superior? Thanks

A:

Thank you for your recent inquiry.

The preferred in vitro test to detect the characteristic IgG anti-FC epsilon receptor antibodies found in patients with "autoimmune urticaria" is called "IGERAB Anti-IgE Receptor Antibody". It is available from the National Jewish Laboratory.

Copied below is a web link to the site at the National Jewish Laboratory containing the description of this test, and giving the instructions as to how to order it (see "test menu" link below).

There is some confusion and controversy about the CU index. I have placed, below, another link (Allergy Notes link) for you to view a discussion about this test.

Finally, one can do an in-office, in vivo test by simply drawing blood, taking the undiluted serum and injecting it intradermally into the patient's forearm as you would do an intradermal test for specific IgE to allergen.

Thank you again for your inquiry and we hope this response is helpful to you.

Test Menu Link:
http://www.testmenu.com/public/cltdDetail.aspx?crud=Retrieve|52af7648-e03c-47aa-945f-6629d687c908

Allergy Notes Link:
http://allergynotes.blogspot.com/2009/12/what-is-chronic-urticaria-index.html

Sincerely,
Phil Lieberman, M.D.

We received this anonymous letter and are posting it as an addendum:

Dear Phil,
There is a response to a question regarding tests for autoimmunity in chronic urticaria on the Academy's website that I want to call to your attention. 

The response was to a question regarding the best test for autoimmunity and you indicated that it was the cell marker 203c for basophil activation. First, I do not think one should appear to sanction any particular method since all of them are commercial ventures. Second, the choice of basophil 203c expression as a marker of autoimmunity not chronic urticaria is questionable. When serum-induced basophil histamine release (which is the method Malcolm Greaves and others used to determine the existence of anti-Fcå receptor antibody in patients with chronic urticaria), has been compared to the cell-surface activation marker 203c the correlation was fair, at best. There appears to be controversy in the literature regarding use of CD63, CD69, or 203c as a marker of basophil activation, and 203c seems less reliable than the others (see P. 85 in: Kleine-Tebba J, et al, Diagnostic tests based on human basophils: Potentials, pitfalls, and perspectives, Int Arch Allerg Immunol, 20  06;141:79-90). There is also recent data to indicate that those patients with anti-FcåRI antibody are more difficult to treat and more likely to require cyclosporine or omalizamub based on the CU Index. No treatment conclusions of this sort are a result of publications employing a basophil cell-surface marker.

A number of publications purified the patient IgG to show that antibody is really responsible for the basophil (or mast cell) histamine release but there has been no molecular assessment of whatever is present in patient plasma that upregulates 203c, and the reference above indicates that 203c can be expressed in cells that have not been activated.

Finally, the real controversy regarding the utility of assays relates to binding methods (ELISA, immunoblot) which do not correlate with clinical parameters because the cloned á subunit everyone used has insect carbohydrate attached (cloning vector) to which loads of folks have antibody. Reference to those binding methods in the literature often cast doubt on other methods, thereby creating controversy that should not exist.

Another important issue is that Omalizumab works in those lacking autoantibodies or acts so rapidly on those who have the antibody, that there is insufficient time for down-regulation of the receptor to occur. That is true and it suggests that Omalizumab very likely has a direct effect on basophils and mast cells that we do not understand, but the conclusion also oft-stated that the presence of auto-antibodies is an epiphenomenon, is like saying IgE has nothing to do with asthma because intrinsic asthma exists.

AAAAI - American Academy of Allergy Asthma & Immunology