Another marker for anaphylaxis?
There’s a new six-syllable word bearing down on us, and while the research is still preliminary, you may want to familiarize yourself with it.
The word is carboxypeptidase. That’s right, car-boxy-pep-ti-dase, with the main emphasis on “pep.” What is it? Carboxypeptidase (or more accurately, “Carboxypeptidase A3”) is an enzyme that is released by mast cells when they degranulate. Reference [Henningsson F. Mast cell carboxypeptidase A, a secretory granule component. Doctoral dissertation. Dept. of Molecular Biosciences, SLU. Acta Universitatis agriculturae Sueciae. 2005:86]. Like tryptase [a neutral protease released when mast cells degranulate], it is a neutral protease [an enzyme that can break down polypeptide chains]. To make life easier, let’s abbreviate Carboxypeptidase A3 as CPA3.
Back in 2006, the official designation for mast cell carboxypeptidase was "carboxypeptidase A." However, since then the terminology has been revised. "Carboxypeptidase A" now referes to a pancreatic product, and the designation "CPA3" is used to signify mast-cell CPA.
So why should we care about this tongue-bending technical term? Because a group of seven British researchers [Zhou X, Buckley MG, Lau LC, Summers C, Pumphrey RSH, and Walls AF. Mast cell carboxypeptidase as a new clinical marker for anaphylaxis. J Allergy Clin Immunol. 2006; 117(2):S85] believe that CPA may function as a better marker for anaphylaxis than tryptase.
Researchers and doctors would like to have a blood test that would tell them whether or not what’s happening to a person is anaphylaxis. Tryptase — another enzyme released by mast cells — is the marker that is currently used. But in a significant number of cases, the concentrations of tryptase in circulation do not increase, even when the person is obviously having anaphylaxis.
So, this group of British researchers have tried measuring CPA3 in two groups — people with suspected anaphylaxis and people with systemic mastocytosis (SM) — and comparing it to the results for two control groups — a group of healthy blood donors and a group of people with bronchial asthma.
The results of the study...
PA levels in serum collected in the first eight hours after the onset of an attack were significantly greater than in those of either of the control groups. According to the presentation [Zhou X, Buckley MG, Lau LC, Summers C, Pumphrey RSH, and Walls AF. Mast cell carboxypeptidase as a new clinical marker for anaphylaxis. J Allergy Clin Immunol. 2006; 117(2):S85] the group made at the March 2006 American Academy of Allergy Asthma & Immunology meeting, “In some cases the concentrations were more than 100-fold greater.”
CPA3 levels in serum collected from the people with mastocytosis were also greater than in either of the control groups. And as one would hope, there was no significant difference in the CPA3 levels of the two control groups.
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What does it mean?
Of the cases of anaphylaxis where tryptase levels were elevated, 83% showed CPA3 levels higher than normal. However, CPA3 and tryptase levels were not correlated with each other, which means that the CPA3 wasn’t simply tracking the tryptase level.
And here’s the clincher: In 110 cases of suspected anaphylaxis where tryptase levels were not elevated, CPA3 levels were elevated in 77 people (or 70%). So, measuring CPA3 could provide objective evidence of anaphylaxis in cases where tryptase is not elevated.
However, if you examine the pie chart (on the previous tab) that I created as an illustration for this article, you may notice that there's still a substantial number of subjects who exhibited normal levels of both tryptase and CPA3 while having anaphylaxis. That is why, now, researchers [Simons FE. 9. Anaphylaxis. J Allergy Clin Immunol 2008;121:S402-7; quiz S20] are advocating the development of a panel of of markers that could be used to better corroborate a diagnosis of anaphylaxis. But at this point in time, as Dr. Simons states [Simons FE. Anaphylaxis: Recent advances in assessment and treatment. J Allergy Clin Immunolcite. 2009;124:625-36; quiz 37-8], "Laboratory tests (histamine levels, total tryptase levels, or both) might or might not confirm the clinical diagnosis of anaphylaxis; the history always trumps the test results."
Dr. Andrew F. Walls, one of the researchers working on CPA, commented, “We have since gone on to apply the assay developed for mast cell carboxypeptidase to serum and plasma samples from various forms and categories of mastocytosis. The results indicate that the new test should be useful in diagnosis. We are currently preparing a full paper on this….” Reference [Walls, Andrew F. Personal communication. September 12, 2006].
It sounds like we’ll be hearing more about CPA3 in the months to come. ◊
An earlier version of this article appeared in the Fall 2006 issue of The Mastocytosis Chronicles, the quarterly newsletter of the Mastocytosis Society (TMS).
Page last updated: July 24, 2011