Balk, A.H.M.M. (Aggie)

Burlingham, W.J. (W.)

Claas, F.H.J. (Frans)

DeVito, L.D. (L.)

Jankowska-Gan, E. (E.)

Jutte, N.H.P.M. (Nicolet)

Weimar, W. (Willem)

Erasmus University Digital Repository

Abstracts 121 3 Monitor ing of Heart Transplant  Reject ion Using a Donor-  Specif ic Soluble HLA Class I ELISA IClaas, F.H.J., 2Jankowska-Gan, E., 2DeVito, L.D., 3Jutte, N., 3Balk, A., 3Weimar, W., & 2Burlingham, W.J. IUniversity of Leiden, 2University of Wisconsin-Madison,  and 3University of Rotterdam Our purpose was to ut i l ize a donor-speci f ic  sHLA Class I ELISA to monitor  damage to heart al lografts caused by rejection as an alternat ive to myocardial  biopsy. A group of 21 pts (34 serum samples from 14 pts and 63 samples from 7 pts) were screened for the presence of donor-spec i f ic  HLA Class I before and after cardiac transplant using an HLA- A2-speci f ic  and/or an HLA-B7 specif ic ELISA. The Ab pairs used in the ELISA were: MA2.1 (anti-A2, B57) and CRII-351 (anti-A2, 28) for detect ing HLA-A2, and ME1 (anti-B7, 27) and MB40.2 (anti-B7, 40) for detect ing HLA-B7. The results showed: i) consistent release of donor-  type HLA class i immediately post-Tx (d.l; 15-55 ng/ml) ; and 2) a smaller rise (4-20 ng/ml), during b iopsy-proven rejection episodes. Both HLA-A2 and HLA-B7 levels rose in tandem in patients mismatched for both antigens. Pat ients with no rejection showed no evidence of donor ant igen above background (<3 ng/ml) after the ist post -operat ive day. The major di f f iculty seems to be the problem of background react ivity in patients with HLA-A9 (occasional cross-react iv i ty with the CRII-351 in A2 ELISA) and with certain non-B7, 27 antigens. The technique may be of cl inical value in pat ients with low background values (<3 ng/ml) and to d ist inguish reject ion from systemic infection which may not ca.use a rise in donor-spec i f ic  sHLA. 4 Peptides derived from HLA class I sequences block allorecognition in vitro and in vivo. tClayberger, C., ILyu, S.C., 1Nisco, St., ~Vriens, P., 2Pouletty, P. and *Krensky A. Departments of Cardiothoracic Surgery and Pediatrics, IStanford University School of Medicine, Stanford, CA and 2SangStat Medical Corporation, Menlo Park, CA. We have prepared synthetic peptides corresponding tothe ctl alpha helix of HLA class I molecules and tested them for effects on in vitro immune responses. Some of these peptides were potent inhibitors of T cell differentiation. We evaluated one of these peptides, corresponding to residues 75-84 of HLA-B7, designated Allotrap 07, on heterotopic heart allograft in rats. Treatment of rats with AUotrap 07 either before transplantation r at the time of transplantation caused a slight but significant delay in rejection. Animals given AUotrap 07 in combination with a suboptimal dose of cyclosporine A maintained their grafts indefinetely. When tolerant animals were given a subsequent skin graft from the donor or a third party, they accepted the donor derived graft but rejected the third party graft. Adoptive transfer studies and investigation ofdonor specific ytotoxic T cell precursors showed that tolerance resulted from anergy, and not from clonal deletion of suppressor ceils. Tolerance could be induced if the peptide was administered intravenously, orally and to a lesser extent by subcutaneous injection. These findings indicate that synthetic peptides corresponding to HLA molecules may have important therapeutic effects in humans. 

Monitoring of heart transplant rejection using a donor-specific soluble HLA class I ELISA

http://repub.eur.nl/pub/52892/REPUB_52892_OA.pdf

Monitoring of heart transplant rejection using a donor-specific soluble HLA class I ELISA

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