Interview mit Dr. Mari

Anbei finden sie ein kurzes Interview mit Dr. Adriano Mari, einem der führenden Allergologen in Italien. Dr. Mari hat den ISAC Test in seiner Klinik, dem IDI Hospital in Rom, als weltweit erstes Labor in der Routinediagnostik zum Einsatz gebracht und arbeitet seit Februar diesen Jahres damit. Bisher wurden mehr als 5000 Patienten getestet.

Wir haben ihn nach seinen Erfahrungen mit dem neuartigen Diagnosesystem, sowie mit seinen Patienten und Kollegen gefragt, die mit ISAC Ergebnissen konfrontiert wurden. Ebenso hat uns seine Einschätzung über die Vor- und Nachteile des ISAC Systems interessiert. Finden sie im folgenden das ungekürzte Interview in englischer Sprache.

Q: Why do you use the ISAC test in your routine laboratory ?

A: The first and pragmatic reason is that it’s the only way to test hundreds of allergenic molecules at the same time at a reasonable cost. Furthermore, ISAC testing represent a real new approach to allergy diagnosis. What we generally demand from a diagnostic tool is to give the most objective answer to our diagnostic question, independently of the patient’s and doctor’s opinion on the disease. Allergy diagnosis based on singleplexed methods, either in vitro or in vivo, is too much dependent on allergist’s choice of allergenic preparation to be tested.

Q: What do you see as the major advantage of ISAC testing from the point of your clinical experience ?

A: The chance to test wide allergen panels give us the powerfulness of the molecule-based approach to the allergic disease. Allergenic molecules are definitely markers of risk and describe patient’s sensitization as ever.

Q: What are the drawbacks of the method at the moment ?

A: We are now using ISAC 79b, that means 79 different molecules. They cover the most common allergenic sources. Statistically we have the in vitro diagnosis matching the clinical picture in most of the cases. There is a minority of patients having their sensitization scattered on hundreds of different allergenic sources (organisms). We should be able to have a microarray having all the common and uncommon allergens available capable to to pick up every single IgE raised against any known allergen. This would be the best patient-centered diagnostic and not a epidemiological-based one. I guess we can reach this condition easily by putting together worldwide resources.

Q: What is the advantage of CRD for the clinical everyday practice ?

A: When you see a patient reporting fruit allergy, for instance peach allergy, she/he wants to know the risk of unwanted exposure to peaches. If you test a peach extract you get a single information: peach allergy. If you draw the patient’s profile by using a panel of peach allergen you may say “you are peach LTP positive, you have to avoid peaches at your best as you are at risk of severe allergic reactions not only with peaches” or “you are sensitized to peach profilin, it’s a pretty common sensitization but it caused very mild local (mouth) symptoms and some pollen-related sneezing. You may go on eating fruit without the risk of severe reactions”.

Q: How does the CRD approach influence the treatment of your patients if it does so ?

A: When you see a patient with few sensitization to major allergens from a single organism (e.g. grass pollen), you may decide to treat your patient with immunotherapy with more success as it’s now reasonable that most reliable extracts for immunotherapy do contain major allergens. At the same time when a patient shows multiple allergen sensitization including minor allergens, the risk of an unsuccessful treatment is high. At the moment there are no reports on minor allergen concentration in commercial allergenic extracts.

Q: How do you explain the results to the patients ? In particular, when the patient reacts to a lot of allergens positively ?

A: It’s very easy and patients seem to understand better than when they were tested with extracts. For instances, I carried out some studies on multiple allergen sensitization. At the time of allergenic extracts the reactions to all those tests were really hard to explain. The patient was generally astonished and the doctor (myself) as well. How I could explain a positive skin test to cockroaches when the patient claims that her house is one of the cleanest around the world, and she wants only to know about her reactions to shrimps. Nowadays, we have IgE recognition of several allergens belonging to groups of homologous molecules (e.g. tropomyosins, profiling, calcium-binding proteins, group 1 mite allergens etc). This IgE co-recognition mirrors the immune system response. Thus, if the immune system starts to produce IgE against an epitope from shrimp tropomyosin and this epitope is also carried by the same molecule from cockroaches, you may say to the patient “ I know your’re not exposed to roaches but you’re sensitization to shrimps causes IgE recognition of a molecule in roach extract. If you start sneezing in other indoor environment just ask about cockroach infestation.”
Moreover, there is a general trend to multiple allergenic molecule sensitization. We have the tool to understand and trace this phenomenon.

Q: How do patients accept the new method ?

A: They are very happy about that. They use to ask “Doctor, is it real that you draw a tiny amount of my two-months aged child and I get information on hundreds of allergens including inhalants, foods, latex etc. That has never been possible at once. I have an older child, he had to undergo three or four runs of skin tests before having all performed.” We have definitely overcome the problem of stopping allergy treatment several times to get a full diagnosis.

Q: How do you see the future of allergy diagnosis in a perspective of ten years from now ?

A: We have a great chance to have all allergists performing a molecule-based test before any therapeutic decision. Implementing automation we could have some kind of real time diagnosis. Furthermore, we could compare results from around the world without the bias of non overlapping reagent selection. At this regard I see many surprising results by testing different populations with the same panel of arrayed allergens. This is not only the wish of a researcher, but the need for the community to understand allergic diseases.

Q: Do you think that the typical clinician in allergy should use a tool such as ISAC and what training would you recommend ?

A: I well remember the first time I thought “the interpretation of allergy tests by means of molecule is something different from testing extracts.” I had to accept a soft revolution in my mind turning the center of the allergy world from organisms/tissues to molecules. I invite my colleagues to start to compare their diagnostic results with extracts to those obtained with ISAC. They start from scepticism and after a while they reach an almost fanatic behaviour. I use to support them with a daily training. Patient by patient discussion. I believe that dedicated meeting and courses are useful but nothing is better than a long stage in a molecular allergology setting.

Q: There are any tools available for learning about allergenic molecules and that can be of help in moving from extracts to molecules?

A: There is a web site called Allergome (www.allergome.org). I created the Allergome database some years ago to help myself in summarising data reported on thousands of different papers. Now the Allergome platform is a free tool for acquiring information on every single allergen and many molecular allergologists use this online resource in their daily practice. In the future the Allergome is going to be the very first online database collecting data from routine testing. The ISAC system is suitable to be interfaced with the Allergome platform. It’s really hard to imagine the wealth of information we might get in this way. Allergists and labs will be active parts of this project.

Q: Are there, aside of the clinical/medical aspects, other advantages for your institute (organisational, financial, others) ?

A: No need to say that as soon as we start ISAC testing we attracted patients’ attention to this new method. Now I can say that it was not just the impulse of novelty that attracted them. We are now redesigning strategies to approach the allergic patient. We are discussing with regional health authorities for having ISAC testing as a routine test for early allergy diagnosis. Of course there is an important financial feedback from testing all these patients. I have to say that at the beginning administrative people feared of having some kind of cannibalism of the “classical” diagnostic approach with a neutral overall income balance. Today they are happy and they are searching the way to expand the use of ISAC testing.

Q: What are the benefits of ISAC in comparison to other allergy tests ?

A: Few words: less time, less pain, less paying, more precision, more details, more help in therapeutic decision making.

Q: What are the benefits of ISAC in comparison to conventional Skin-prick tests ?

A: At least one out of four patient is very complex by her/his allergy history. Using skin testing you have to plan several sessions to reach an extract-based diagnosis carrying all the doubts I explained above.
We might imagine a patient entering the allergist office having the ISAC test already prescribed by the family physician, willing to know how to proceed with therapy. Allergists will re-discover their main therapeutic role and a molecule-based immunotherapy will be the magic bullet to treat allergy symptoms, definitely.

Q: Is ISAC useful for allergy testing for children ?

A: Any paediatrician curing allergic diseases has her/his own daily “fight” with one or more kids to perform skin testing. They are forced to reduce the number of allergens to be tested to a minimum, that generally leads to sensitization overlooking. ISAC testing allows us to test the allergic patient regardless of her/his age for the same panel of allergens. Undoubtfuly there are sensitization that are more common in adult subjects, nevertheless there are exceptions and ISAC testing helps to see what is the allergic pattern in a single patient whatever is allergic to common or rare allergens by the age.

Q: If you were a patient, how would you benefit from ISAC ?

A: I got hepatitis working in a lab more than 25 years ago. At that time a friend, a doctor, observed my jaundice but no markers were available. Some year later I’ve been tested with hepatitis virus markers and I knew that I was infected by HBV, but the virus was cleared from my body as I got immunity and I’m not at risk of any chronic hepatitis or something more serious. Having a molecule-based allergy diagnosis performed by ISAC, I would say “finally I can get the same ultra-fine diagnosis that I would get having another disease already having a molecule-based diagnostic approach”.