Dr. med. univ. Ferdinand SILBERBAUER

Immune-tolerance-induction - decisive progress on the field of the organ-transplantations-

Transplantation-surgeons and organ-receiver  all  over the world disire already since years a method, which makes the repulsion-reaction at transplanted organs impossible. This method was by me already 1990 [ 3] discussed, but unfortunately without positive reaction of competent surgeons. Now however appeared by examples from Israel, Italy and the USA, that my theory is right. In this report at first are theoretical considerations and then concrete examples of immune-tolerance-induction discussed.

We know already on the one hand of the medicine-study and on the other hand form the practical medical experience, that binovular twins with different blood-groups, which were connected with each other through their placentas, all their life tolerate the blood-group of the other twin. Likewise we know, that bacterial infections in the bone-marrow by own power are not able to be refused, and also we know, that micro-metastases of malignomas in the bone marrow the defense of the malignoma prevent.

Now, what have this three proved facts common? It is not among other things the poor blood-perfusion in the bone marrow, which prevents the defense in the bone marrow, how once a colleague maintained [4], but the common fact is the contact of strange-anti-genes with the unripened immune-system of the bone-marrow! This contact releases now in the bone marrow the formation of immune-tolerance-factors, which migrate from there out into the periphery and program the hole immune-system so, that no defense-reactions against that aforsaid antigens occure. This can now be strange antigens of the HLA-system or bacteria or allergens. At antigens of the HLA-system and allergens is here the immune-tolerance desired, at bacterias however undesired.

How can we now concrete at organ-transplantations the repulsion-reaction prevent?

While we win from the organ-donor additional HLA-competent cells and implant them into the bone-marrow-space of the organ-receiver. This can f.i.. be cells of the abdomen-net or  bone-marrow stem-cells, which are problemless able to be taken out.

Merley at the bone-marrow-transplantation it occures otherwise: if the leukemia-sick man after annihilation of his own bone-marrow from the received secondary bone-marrow has a graft-versus-host reaction (GVHR) or such a reaction is to be feared, so one takes a bloating of HLA-competent cells from the receiver and injects them into the bone-marrow-space of the receiver, where there is the unripened immune-system of the secondary bone-marrow. Thereby is also here induced the desired immuntolerance.

And now to the concrete examples of organ-transplantations, at which this principle has become realized: Dr. Susanne Ildstad [ 2] at the university of Pittsburgh, leaded after experiments at the mouse in a pilot-study at five patients an organ-transplantation, whereby as a concomitant action also bone-marrow from the organ-donor was additional transplanted, when before the T-helper-cells were out of it remoted, but the so-called promote-cells were leaved behind. It came neither to an organ-repulsion nor to a GVHR, although at four patients only three surface-antigens of the HLA-system instead of the otherwise usual six corresponded and at one organ-reciver generally no HLA-corresponding existed.

What had happened? HLA-competent cells of the donor came into contact with the unripened immune-system in the bone-marrow-space of the receiver. But also reverse originated a contact of HLA-competent cells of the receiver with the unripened immune-system of the donor, because the stem-cells of the donor, likewise how these of the receiver divide themselves and build during ther ripening HLA-surface-antigens. It came thus to a cross-immuntolerance-induction. Therefore the colleague would have could spare the remotion of the T-helper-cells and would have the same success, i.e., she needed at none of the organ-recivers immun-supressivas.

Proof: Prof. Yair Reisner [1] from the Weizmann-institute in Israel leaded at numerous leukemia-sick persons a bone-marrow-transplantation without annihilation of the receiver-bone marrow before. Also here the HLA-surface-antigens corresponded unconventional rarely, and it came also after months to no GVHR. Also here no immunsupressevia were required. But thereby the leukaemia-stem-cells were not annihilated, a disadvantage for the further sickness-progress.

Right would have been, to destroy the leukemia-cells, then to lead a bone-marrow-donation and simultaneous to implant HLA-competent cells out of the body of the receiver into his bone-marrow-space, in order, that an intensive contact with the unripened immune-system of the secondary bone-marrow occurs.

Worthy readers, I hope, among you exist competent avantguardists, who wish to transpose the logic of this report into fact.

sources:

1.) BILD DER WISSENSCHAFT Nr.4/1995, S.10, 11, "Die Menge machts"
2.) BILD DER WISSENSCHAFT Nr.6/1995, S.106, 108 "Milde Spende"
3.) Dr. F. Silberbauer, "Zur Immuntoleranzinduktion bei Organtransplantationen", ARZTE WOCHE, 4.Jahrgang Nr. 4, S.6
4.) Doz. Dr. Christoph Zielinski, "Tumore sind wenig antigen", ARZTE WOCHE, 4. Jahrgang, Nr.4, S.6
5.) Medical Tribune Nr.40, 4.Okt. 1991, S.16 "Artfremde Transplantate überleben ganz ohne Immunsupression!
6.) Arzt und Praxis,49. Jahrgang, 731, S.560, "Lebertransplantation bei Erwachsenen"