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Graft-vs-host disease (GVHD) associated with cadaveric renal transplantation from an HLA-homozygous donor
III
Abstracts
p605
P604 HLA CLASS II DNA TYPING USING OC ULAR TISS UE AND IT'S USERJLNESS IN CO RNEAL T RANSPLANTAT ION Saio T, Munkh bat B, Hagihara M, Tsuchida F, Shimazaki J' , Tsubota X" , Tsuji X Tokai University, Kanagawa; "Tokyo Dental College, Tokyo, Japan We peIfonned HLA DNA-typing using ocular tissue and a benefit of HLA class II compatibility in corneal transplantation was evaluated. Five eye balls were dissected under sterilized condition into 11 component tissues and were subjected to genomic DNA extraction.lt was proved that genomic DNA could be extracted from ocular tissue co mponents except lens. The relationship of the level of HLA class (( antigen match ing and corneal transplant outcome was studied retrospectively. Sixty nine donor-recipient pairs at low and high risk groups were divided into subgroups according to having or not having rejection episode and to the level of HLA class 11 antigen matching for DRB I , DQB I and DPB I alleles. In low risk recipients, there was no relationship between the incidence of rejection andthe level of HLA class II matching. The same results were also shown in high risk recipients when analysed HLA-DRB 1 and DQB 1 matching. Interestingly, the incidence of rej ection was significantly lower in high risk recipients with 1-2antigens compatible for DPB 1 allele (p=O.OO6 I, RR=9.0 , x~5.72) . Th ree corneal tissue samples were examined for the expression of HLA class 11 antigens by immunohistochemical staining. Corneal epitheliums which were on acute rejection, showed high level of HLA-DP expression. HLA DNA PCR-RFLP typing could be easily peIfonned using only a small part of ocular tissue and especially it is useful for the typing of donor HLA without harvesting blood samples. There is a significant relationship between the HLA-DPB I compatibility and rejection in high risk group. HLA-DP antigens may involved in immunological reactions after corneal transplantation.
p606
Ca"n_1 T ...n_l.n_tllan .nd TI•••u. M.tlahlnll
~:~~~~~\~g~~~f~~~~~~an~~~1endship Hospi t -
N.B Un iv . Ve sor-For-eed exper iment study on thi rt y-three high r isk pat ients of corneal vascula r izat ion fr om donors who were
s el ec t ed on th e basi s of
B
negat i ve ]YJlPhocyt e c r os s - mat ch .
ABD antigen blood group cospat ib i I itv.and maximised HLA- A, HLA-B and HLA-DR ant is en matc hing before sur s er . I. the HLA-A, B, C, DR , DO locus antigen wer e deter mi ned on t hirty -three high ri sk patien ts and twent y th ree hea lt hy adul t , e leven cases could be we i i satcheed HLA group fr om who were se lected on the bas is of obtain ing donor - re cipient a nt lgen sa t ched i n HLA- A, B or t wo DR or one DR and one ofA, B Locus in terllS of t he e ight h ibt er nat iona l coapat ib i I i ty meeti ny data: t wenty t wo case s coul d be poor ly eat chad HLA gr oup for s hor t i nr of above condi t ions , wi t h aean fol low- up t iee of fifteeh (e ight ot t wenty one l mont hs . 2. The sur v i val rate of graf t :we 11 ""tched gr oup was90.90% -- 81. 82'10 compar ed to 68.1 8- 31.8 2% f or poorly sa tc hed one. The for oer was apparen t ly s uch higher t han t he Iatt er , 3. The re ject ion r at e was 51. 50 % for th i r t y- three pat ient s at high r isk froo donors who wer e s e lected on the basi s of negat i ve lymphocyt e cross aat ch, This s uss es t ed Lhat t he negative lymphocyt e cross match t es t could play xome cer t a i n r o le in redu c i m the re jecti on ra t e . Our res ules demons t r at ed: Fi rst . lower incidencee of cornea l gr aft failure fr om a l lograf t re.iec t on . hen ti ss ue matchi ng (ese ic ia 1jyHLA aa t ch ing) was used f or s e I eet i ns donor in hig h risk pat ient s wi th corneal vas cul ar izat ion. Second, there . as no corre la t ion bet wen t he ruab er of HLA ant igen mat ching and the r ej ect ion r ate .
P607
ANALYSIS OF HLA-DRBI MOLECULAR MATCHING BASED ON THREE DIMENSIONAL STRUClURE IN CADAVERIC RENAL TRANSPLANTATION
MOLECULAR HLACLASS n GENE COMPATIBILITYDOES NOTAPPEAR RELEVANf INTIlE DEVELOPMENTOF ACUTEREJECI10NIN LIVERTRA.'1SPLANf. ML"RO ~l
rom
GARctA-A.LONSO
A. A.'TANON J. !\UNGtlliLA A MAJUN L, SA~H1s..p..K)RElL M J BERJ.EJO J A. M.
*
A....'O ALvARFZ·l6PFz M. R.
S.Takahara,M.Sada. M.Tada, M.Haton. J.D. Wang, T.Tsuji,A. Okuyama Osaka University, Dept. of Urology. Osaka, Japan
Secci6n de Jnrrmnologia, ·Ser.-icio de Anatomia Patologica, H. U. VIrgen de la Anixaca. Murcia. SPAIN.
The mechanism of alloantlgen presentation to CD4+ helper T cell by HLA class II molecule-peptide complexand the analysis of peptide-binding site inthe groove are well understood. In this study, we performed DRBI genotyping of cadaveric renal transplant pairs. and examined a correlation between recipientdonor molecular matching and ac ute rejection episode . 126 cases who underwent first cadaveric renal transplants were performed the ORB1 genotyping using PCR-LiPA and PCR-SSP methods . The frequency of mismatched numbers of DRBI. amino acid residues on the a helix and {3 pleated sheet (coden 9-86) was signifICantly higher in the rejection +Ve group (16.5± 5.2) as compared with the rejection -ve group (10.7 ± 5.1; p< .OI). Similar data was observed on mismatched amino acid residues number of f3 pleated s heet (rej. - ve: 10.7±3.9, rej. -ve: 6.5±3.6)(p< .01). The frequencyof mismatched number of codon 26, 26. 30, and 36 of second variable region on the {3 -pleated sheet and codon 57, and 60 on the a helix was higher in the rejection - ve group as compared with rejection -ve group. The permissible!
The present study examines the effect of theHLA-DRB and DQBI compatibility between donor-receptors andtheir relatiooship with acuterejectiCII in livertransplant. The study was carried out in 140 livertransplants, excluding 28 grafts in much·the DNAtyping was unknown and 27 mJich were re-transplanted. The acute rejectiCII diagnosis wasbased 00 cooYenlicnaIclinical and anaIllmOp3lboIogicalcriteria, The analysis of DRB and DQBI polymorphism and the aate rejectiCII ocammce showed that graft performed in total DR mismatch eodubited37% of acute rejecticn v.tlereas, those dale with I or 2 DR matd1es showed an acute rejectioo percaItage of 53%and 50"10 respees showed 40"/0, 510/ .. and 38% of acuterejectiCII . 1-IowlMrr, DO otatistically significant difrereoces were observed in any cases. CanariJy, cmsidering the recipifm HLA DQBI status, a restrid.ed effect to the HLA-DQBI*0302 aUele was observed, mJich appeared indepoodent of their HLA-DR4 linkage, an effectthat was DOt observed analysing the dooor HLA DQB1"0302influenceor donor-receptor HLADQB1"0302 match. In summary, themolecular HLA-DRBandHLA-DQBl results observed in this study, could indicatethat HLAclass II compatibility between liver dcoor-receptor does not relevant to the development of the acuterejectiCII in livertransplant. CCIItrariIy, the recipient HLA-DQBI geeetic status appears to be a determining factor in the livergraft rejecticn or acceptance,
immunogen ic DRlDRB1 co mbination base d on substituted amino acid of codo n
26, 28, 30, 31, 38, 57, and 60 were observed. The permissible combination was same aminoacidresidues(FDYFVDY: ORIS, 16,4,8, II, 13, FDYFVSY: DR4. 8, 13, FEYFVDY: DR3, 14). These results s uggest that molecular matching of recipient-donor wili bring on the improvement of organ transpla nt success rate.
p609
P608
GRAFT-VS-HOST DISEASE (GVRD) ASSOCIATED WITH CADAVERIC RENAL TRANSPlANTATION FROM AN HIA-HOMOZYGOUS DONOR JtffrrJ McConrt4Ck, EtOOud A,r""" Robm Collins, Uvry MtI/Q.. Mortin MoJ, St.... Ho, s, B4y1or Univemt] M,16aJl(Atilti', Da1l4s, r,XJJS GVRD l ollow., , OfU0'l'U' trrlRspUuuiztiml is IlJI"t ON! _~ 10 U.~, lronsp/1«NJ Pro4uds, III , MIt in.sItuu:st-TX Ifj4 IMJt tltted dOlUJl" crlI.r, hiJ" rnr, comIoti.. y-ehrvmos.... f7SR ondJsUIlt 6.5mos,hiJ...d XY-eiIromtli" CORI!itiDRbrg trgImtn wsbrg OKT.ItulIil>odJ twI hlfh dosestfT0id3 l o1bl"•• bJ iJlfMSilHt 01GCSF moMliud puipMraJ blood SlUt ell a jlOl1I JuT Qtln Ol'. SJu expired Oil "'J 12 Ihu 10 s}Sltmic ...".tF/losis. UNOSpoIi£yspetificollJ,
.....u,
INCREASED INCIDENCE OF VIRAL HEPATITIS IN HLA COMPATffiLE LIVER TRANSPLANT RECIPJENfS ReneJ . Duquesnoy, Rafael Manez, Anthony J. Demetris University of Pittsburgh Medical Center, Pittsburgh, PA, USA Several years ago, our group reported HLA compatibility is associated with lower liver transplant survival. These findings led to the concept that HLA has a dualistic role in liver transplantation: HLA matching reduces rejection but will enhance other immunological mechanisms of liver allograft injury, particularly in patients at risk of developing recurrent autoimmune disease or infection. Subsequently, other groups have also reported lower survival rates of HLA liver transplants. Here we present our experience on the influence of HLA compatibility on viral hepatitis in liver transplant patients. Matching for HLA-DR promotes the development of both primary and secondary CMY hepatitis. The relative risks are 4.8 and 7.6, respectively. While the incidence of chronic rejection is higher in patients with CMY hepatitis, there appear no associations between HLA compatibility and the incidence of chronic rejection, matching for HLA-DR is associated ",ith an earlier onset of chronic rejection irrespective of CMY hepatitis. The development of recurrent hepatitis due to HBV and HCV infection is higher for HLA-B matched liver transplants, the relative risk is 2.8. The associations between HLA matching and viral hepatitis may reflect MIlC -restricted, viral antigenspecific mechanisms of immune injury to infected allografts. These findings provide further support of the dualistic role of HLA in liver transplantation.
Abstracts
p605
P604 HLA CLASS II DNA TYPING USING OC ULAR TISS UE AND IT'S USERJLNESS IN CO RNEAL T RANSPLANTAT ION Saio T, Munkh bat B, Hagihara M, Tsuchida F, Shimazaki J' , Tsubota X" , Tsuji X Tokai University, Kanagawa; "Tokyo Dental College, Tokyo, Japan We peIfonned HLA DNA-typing using ocular tissue and a benefit of HLA class II compatibility in corneal transplantation was evaluated. Five eye balls were dissected under sterilized condition into 11 component tissues and were subjected to genomic DNA extraction.lt was proved that genomic DNA could be extracted from ocular tissue co mponents except lens. The relationship of the level of HLA class (( antigen match ing and corneal transplant outcome was studied retrospectively. Sixty nine donor-recipient pairs at low and high risk groups were divided into subgroups according to having or not having rejection episode and to the level of HLA class 11 antigen matching for DRB I , DQB I and DPB I alleles. In low risk recipients, there was no relationship between the incidence of rejection andthe level of HLA class II matching. The same results were also shown in high risk recipients when analysed HLA-DRB 1 and DQB 1 matching. Interestingly, the incidence of rej ection was significantly lower in high risk recipients with 1-2antigens compatible for DPB 1 allele (p=O.OO6 I, RR=9.0 , x~5.72) . Th ree corneal tissue samples were examined for the expression of HLA class 11 antigens by immunohistochemical staining. Corneal epitheliums which were on acute rejection, showed high level of HLA-DP expression. HLA DNA PCR-RFLP typing could be easily peIfonned using only a small part of ocular tissue and especially it is useful for the typing of donor HLA without harvesting blood samples. There is a significant relationship between the HLA-DPB I compatibility and rejection in high risk group. HLA-DP antigens may involved in immunological reactions after corneal transplantation.
p606
Ca"n_1 T ...n_l.n_tllan .nd TI•••u. M.tlahlnll
~:~~~~~\~g~~~f~~~~~~an~~~1endship Hospi t -
N.B Un iv . Ve sor-For-eed exper iment study on thi rt y-three high r isk pat ients of corneal vascula r izat ion fr om donors who were
s el ec t ed on th e basi s of
B
negat i ve ]YJlPhocyt e c r os s - mat ch .
ABD antigen blood group cospat ib i I itv.and maximised HLA- A, HLA-B and HLA-DR ant is en matc hing before sur s er . I. the HLA-A, B, C, DR , DO locus antigen wer e deter mi ned on t hirty -three high ri sk patien ts and twent y th ree hea lt hy adul t , e leven cases could be we i i satcheed HLA group fr om who were se lected on the bas is of obtain ing donor - re cipient a nt lgen sa t ched i n HLA- A, B or t wo DR or one DR and one ofA, B Locus in terllS of t he e ight h ibt er nat iona l coapat ib i I i ty meeti ny data: t wenty t wo case s coul d be poor ly eat chad HLA gr oup for s hor t i nr of above condi t ions , wi t h aean fol low- up t iee of fifteeh (e ight ot t wenty one l mont hs . 2. The sur v i val rate of graf t :we 11 ""tched gr oup was90.90% -- 81. 82'10 compar ed to 68.1 8- 31.8 2% f or poorly sa tc hed one. The for oer was apparen t ly s uch higher t han t he Iatt er , 3. The re ject ion r at e was 51. 50 % for th i r t y- three pat ient s at high r isk froo donors who wer e s e lected on the basi s of negat i ve lymphocyt e cross aat ch, This s uss es t ed Lhat t he negative lymphocyt e cross match t es t could play xome cer t a i n r o le in redu c i m the re jecti on ra t e . Our res ules demons t r at ed: Fi rst . lower incidencee of cornea l gr aft failure fr om a l lograf t re.iec t on . hen ti ss ue matchi ng (ese ic ia 1jyHLA aa t ch ing) was used f or s e I eet i ns donor in hig h risk pat ient s wi th corneal vas cul ar izat ion. Second, there . as no corre la t ion bet wen t he ruab er of HLA ant igen mat ching and the r ej ect ion r ate .
P607
ANALYSIS OF HLA-DRBI MOLECULAR MATCHING BASED ON THREE DIMENSIONAL STRUClURE IN CADAVERIC RENAL TRANSPLANTATION
MOLECULAR HLACLASS n GENE COMPATIBILITYDOES NOTAPPEAR RELEVANf INTIlE DEVELOPMENTOF ACUTEREJECI10NIN LIVERTRA.'1SPLANf. ML"RO ~l
rom
GARctA-A.LONSO
A. A.'TANON J. !\UNGtlliLA A MAJUN L, SA~H1s..p..K)RElL M J BERJ.EJO J A. M.
*
A....'O ALvARFZ·l6PFz M. R.
S.Takahara,M.Sada. M.Tada, M.Haton. J.D. Wang, T.Tsuji,A. Okuyama Osaka University, Dept. of Urology. Osaka, Japan
Secci6n de Jnrrmnologia, ·Ser.-icio de Anatomia Patologica, H. U. VIrgen de la Anixaca. Murcia. SPAIN.
The mechanism of alloantlgen presentation to CD4+ helper T cell by HLA class II molecule-peptide complexand the analysis of peptide-binding site inthe groove are well understood. In this study, we performed DRBI genotyping of cadaveric renal transplant pairs. and examined a correlation between recipientdonor molecular matching and ac ute rejection episode . 126 cases who underwent first cadaveric renal transplants were performed the ORB1 genotyping using PCR-LiPA and PCR-SSP methods . The frequency of mismatched numbers of DRBI. amino acid residues on the a helix and {3 pleated sheet (coden 9-86) was signifICantly higher in the rejection +Ve group (16.5± 5.2) as compared with the rejection -ve group (10.7 ± 5.1; p< .OI). Similar data was observed on mismatched amino acid residues number of f3 pleated s heet (rej. - ve: 10.7±3.9, rej. -ve: 6.5±3.6)(p< .01). The frequencyof mismatched number of codon 26, 26. 30, and 36 of second variable region on the {3 -pleated sheet and codon 57, and 60 on the a helix was higher in the rejection - ve group as compared with rejection -ve group. The permissible!
The present study examines the effect of theHLA-DRB and DQBI compatibility between donor-receptors andtheir relatiooship with acuterejectiCII in livertransplant. The study was carried out in 140 livertransplants, excluding 28 grafts in much·the DNAtyping was unknown and 27 mJich were re-transplanted. The acute rejectiCII diagnosis wasbased 00 cooYenlicnaIclinical and anaIllmOp3lboIogicalcriteria, The analysis of DRB and DQBI polymorphism and the aate rejectiCII ocammce showed that graft performed in total DR mismatch eodubited37% of acute rejecticn v.tlereas, those dale with I or 2 DR matd1es showed an acute rejectioo percaItage of 53%and 50"10 respe
immunogen ic DRlDRB1 co mbination base d on substituted amino acid of codo n
26, 28, 30, 31, 38, 57, and 60 were observed. The permissible combination was same aminoacidresidues(FDYFVDY: ORIS, 16,4,8, II, 13, FDYFVSY: DR4. 8, 13, FEYFVDY: DR3, 14). These results s uggest that molecular matching of recipient-donor wili bring on the improvement of organ transpla nt success rate.
p609
P608
GRAFT-VS-HOST DISEASE (GVRD) ASSOCIATED WITH CADAVERIC RENAL TRANSPlANTATION FROM AN HIA-HOMOZYGOUS DONOR JtffrrJ McConrt4Ck, EtOOud A,r""" Robm Collins, Uvry MtI/Q.. Mortin MoJ, St.... Ho, s, B4y1or Univemt] M,16aJl(Atilti', Da1l4s, r,XJJS GVRD l ollow., , OfU0'l'U' trrlRspUuuiztiml is IlJI"t ON! _~ 10 U.~, lronsp/
.....u,
INCREASED INCIDENCE OF VIRAL HEPATITIS IN HLA COMPATffiLE LIVER TRANSPLANT RECIPJENfS ReneJ . Duquesnoy, Rafael Manez, Anthony J. Demetris University of Pittsburgh Medical Center, Pittsburgh, PA, USA Several years ago, our group reported HLA compatibility is associated with lower liver transplant survival. These findings led to the concept that HLA has a dualistic role in liver transplantation: HLA matching reduces rejection but will enhance other immunological mechanisms of liver allograft injury, particularly in patients at risk of developing recurrent autoimmune disease or infection. Subsequently, other groups have also reported lower survival rates of HLA liver transplants. Here we present our experience on the influence of HLA compatibility on viral hepatitis in liver transplant patients. Matching for HLA-DR promotes the development of both primary and secondary CMY hepatitis. The relative risks are 4.8 and 7.6, respectively. While the incidence of chronic rejection is higher in patients with CMY hepatitis, there appear no associations between HLA compatibility and the incidence of chronic rejection, matching for HLA-DR is associated ",ith an earlier onset of chronic rejection irrespective of CMY hepatitis. The development of recurrent hepatitis due to HBV and HCV infection is higher for HLA-B matched liver transplants, the relative risk is 2.8. The associations between HLA matching and viral hepatitis may reflect MIlC -restricted, viral antigenspecific mechanisms of immune injury to infected allografts. These findings provide further support of the dualistic role of HLA in liver transplantation.