Haematologica 2000;85:supplement to no. 10 - Supplements ...

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C.M. Kessler
ously. Do you see differences in the epitope
repertoire depending on the actual disease the
auto- antibody is associated with
KESSLER: I don’t believe that there have been
enough antibodies isolated in this group of
patients to answer that question but it is a very
important question and hopefully with more collaboration
worldwide we may be able to answer it.
HYBERG: When you look at tolerance induction
in your patients do you see differences which
depend on the disease with which it is associated
with the appearance of the auto-antibody
Do you see long-lasting effects for instance if the
auto-antibodies are associated with other auto
immune diseases
KESSLER: I’m going to let Dr. Nemes describe
his own data but I can tell you that other studies
in the literature suggest these are all durable
responses. There is no differentiation among the
various autoimmune diseases as to whether you
can achieve a complete remission.
INGERSLEV: I want to emphasize though that
we have suffered in many cases an unavoidable
tendency of hematuria when using cyclophosphamide.
This has been a major problem and so
we have been seeking a new standard procedure
in which we have pointed to the use of
cyclosporine as the most likely. Do you think we
can have some help in future studies being set up
in the way that you and Dr. David Green and
others have done. All centers have very few
patients and we need to have these multi-center
studies in order to learn from our patients.
KESSLER: I certainly agree with you. Unfortunately,
Dr. Green with his own prospective control
study which he has been doing for over nine
years has gathered a very small number of
patients. Ideally, what you are saying is correct
and hopefully there will be much more interest in
the future so that worldwide participation will
be facilitated.
SULTAN: Dr.Kessler, do you think that the
group of patients who developed an inhibitor
during pregnancy or after delivery are affected
by the same mechanism, for instance associated
with solid tumors Do you think that these
patients should have special treatment-not giving
immunosuppressive agents I would like to bring
together the immunologists who are gathered
here to share their ideas on the development of
inhibitors in cases of pregnant women. I would
like to know if there is a specific immunologic
context which might explain the appearance of
an inhibitor antibody.
KESSLER: I am not an immunologist, but I am
fascinated by the fact that the placenta elaborates
so many substances which can thereby activate
lymphocyte release of cytokines. Whether or
not the cytokines are the same for all of the other
types of auto-antibody inhibitor situations I
can’t say, but they certainly don’t respond in the
same way. Perhaps one of the immunologists
present could shed some light on this matter
BAUDO: Just a comment from the Italian Registry
of acquired inhibitor. We have collected the
data from about 80 patients up to now. The age
of occurrence is higher in men than women. The
mortality rate is about 15%, but 50% of the
deaths were related to bleeding. The data from
immunosuppressive therapy with prednisone
suggest that sustained remission is only obtained
with the association of cyclophosphamide or
azathioprine with prednisone. The rate of remission
is over 60%.
SULTAN: But you are talking about the whole
group of patients with auto-antibodies and not
especially about those appearing during pregnancy.
ALEDORT: Dr. Kessler, I think the issue of the
potential for recurrence in another pregnancy is
a very important one and I’ve had several
patients who have had horrendous clinical problems
when they developed the inhibitor and yet
they want more children. I think it is very important
and I’ve tried myself to collect local data as
there is very little information on this and the
likelihood of recurrence and what influences it.
There are enormous implications for family planning
and we need to focus some attention on
that issue in the future. It may not be as simple
as it appears. We possibly need to look at epitopes
and there could be something to know
about the babies’antigens in order to predict
whether the patient should abort or possibly
avoid becoming pregnant again. There are a lot
of unresolved issues that we need to look at.
KESSLER: Certainly, I agree with you.
SULTAN: Dr. Aledort is there a chance that the
inhibitor to factor VIII in pregnant women could
be an allo-antibody
ALEDORT: Yes, it’s possible. It may well be that
it is a response to a factor VIII molecule in pregnancy
that is different because it occurs late. It’s
not particularly early. It frequently occurs at the
time of delivery at which time there is a mixture
of maternal and fetal blood. It may very well
occur during that time. It is very unusual that it
happens in the first trimester or for that matter
in the second. Frequently, the bleeding occurs
right after the delivery and the antibody is present.
We know very little about all this.
KESSLER: I think you are right. You have made
an astute observation based on the idea that the
women who do develop recurrences do often
show up in the late first trimester with their
inhibitor whereas their original inhibitor did not
develop until the post- partum period.
MARTINOWITZ: I would like to draw your
Haematologica vol. 85(supplement to n. 10):October 2000