Prospektive Analyse des vorteilhafen Einflusses von HLA-matching auf molekulabiologischer Ebene auf das klare, abstoßungsfreie Transplantatüberleben nach perforierender Keratoplastik

Penetrating keratoplasty is the most commonly performed transplantation worldwide. Mid term clear graft survival high as 80% in normal risk situations but immune reactions directed against the vulnerable, non-mitotic transplant endothelium remain important reasons for graft failure in the long run. Although the protective effect of HLA matching is now well-established, it is still not widely performed as the major disadvantage has so far been the additional time on the waiting list when seeking for a completely HLA compatible donor. However, this waiting time has recently been demonstrated to be well below two years for most individuals when one of six HLA mismatches (HLA-A/-B/-DR) is accepted (2). It has been known for longer that certain HLA mismatches do not deteriorate graft prognosis in kidney transplantation. For HLA class I loci, the structural basis of this phenomenon has recently been established: each HLA antigen comprises of a string of well defined epitopes, partitioned into amino-acid triplets (“triplet-string”). The degree of matching at the triplet-string level is assessed by determining whether or not each of these triplet-epitopes is also found in the corresponding positions within any of the patient’s own HLA-A and –B triplet-strings. By accepting only HLA mismatches, comprising of triplets also present in the recipient, time on the waiting list might be substantially shortened (due to acceptance of some mismatches) without deteriorating graft prognosis. Upon confirmation of the beneficial effect of matching at the amino-acid triplet-level with respect to rejection-free clear graft survival, evidence-based recommendations for reasonable degree of histocompatibility (and recommended minimal waiting period in normal-risk situations) can be made. This would help in reducing overall graft failures in the long run and make penetrating keratoplasty even more successful. Histocompatibility standards of other allotransplantations might benefit from the proposed study as well.

Weitere Informationen: http://www.ukl.uni-freiburg.de/aug/homede.html
Ansprechpartner: Dr. med. Daniel Böhringer
Tel: 4006
Email: boehringer@aug.ukl.uni-freiburg.de

Projektbeginn: 2004
Projektende: 2008

Prof. Dr. med. Thomas Reinhard
Stellvertretung: Dr. med. Philip Maier
Albert-Ludwigs-Universität Freiburg
Augenklinik
Abteilung Allgemeine Augenheilkunde mit Poliklinik
Killianstrasse 5
79106 Freiburg

Telefon: +49 (761) 270-40060
Fax: +49 (761) 270-40630
Email: augenklinik.direktion@uniklinik-freiburg.de
http://www.uniklinik-freiburg.de/augenklinik.html

Hornhaut, Transplantation