Discussion among members of the CSSISG about ANCA tests

Most CSS patients are familiar with blood tests that measure eosinophils, CRP (C-reactive protein), and sed. rate. But what is the ANCA test? Furthermore, there seemed to be some confusion among CSS patients on the CSSISG message board as to how useful this test is in monitoring disease activity. The following is what came up in the discussion of ANCA tests:

ANCA means antineutrophil cytoplasmic antibodies, and can be divided into 2 kinds:
p-ANCA, which are antibodies mostly against myeloperoxidase (MPO) and are found in CSS and in other vasculitides, and c-ANCA, which are antibodies mostly against proteinase 3 (PR3) and are seen mostly seen in Wegener's disease.

ANCAs are checked by a serological test called Immunofluorescence Microscopy (IFM).

Blood tests will show if your ANCA test is positive or negative. If positive, it shows if there are PR3 or MPO, and it also shows the titer level. The titer shows how high the ANCA level in your blood is.

The blood serum is titrated by doubling dilutions. The number on your tests results will show the highest dilution at which the ANCA fluorescence pattern is still visible, and it will look like this- 1:20, or 1:40, 1:80 etc. If ANCA tests are positive, these titers should be compared from one visit to the other.

There is more and more evidence that ANCA are involved in the pathogenesis of small vessel vasculitis. In an article by Dr. R.J. Falk & Dr. G.C. Jennette "ANCA are Pathogenic - Oh Yes They Are!" (http://jasn.asnjournals.org/cgi/content/full/13/7/1977) it was said that ANCA are more than a serological marker of disease. They can stimulate leukocytes to undergo a respiratory burst and degranulate primary granular constituents. This finding supports a direct pathogenic role for ANCA.

The confusing thing is that not all CSS patients are ANCA positive. According to Prof. dr. Loic Guillevin only one third to one half of all CSS patients are ANCA positive - mostly MPO positive, sometimes PR3, sometimes both.

And furthermore, there seems to be only a loose correlation between ANCA titer and disease activity (65%).

To add to the confusion: the literature shows that some vasculitis patients have continuously positive ANCA without disease activity, while others test negative on ANCA even when they do have active disease.

Now, what does that mean for us, should we pay attention to it, or not?
Most of our doctors check eosinophil level, CRP, sed.rate etc. very regularly, and ANCA level seldom, or not at all.

What vasculitis specialists seem to agree on is that the ANCA test could provide valuable supportive evidence for a vasculitis, meaning that being tested ANCA positive could be helpful, if there is still doubt, in diagnosing an autoimmune vasculitis.
When it comes to the ANCA test being useful in monitoring disease activity there seems to be some controversy, and the specialists are less certain. A significant rise in ANCA may proceed a relapse, but this is not always the case, so a persistence of or a rise in ANCA is not a definite warning signal for disease activity!

It seems reasonable to say that the ANCA test - for the time being - should at best serve as a complementary piece of information to a thorough clinical assessment, evidence of disease activity, and the measurement of inflammatory markers, such as CRP.

It was also mentioned that the ANCA test is still an area for research in the vasculitides, and hopefully future findings of such research may yield a better understanding of the importance of ANCA in Churg Strauss Syndrome.

This is how the ANCA test was discussed among CSS patients on the CSSISG message board.

Many thanks to Christophe and Bruce for their helpful information.

Marian Mesker