Role of Ia-Like Products of the Main Histocompatibility Complex in Conditioning Skin Allograft Survival in Man J. Dausset, … , T. Meo, F. T. Rapaport J Clin Invest. 1979;63(5):893-901. https://doi.org/10.1172/JCI109389. Research Article This report correlates the survival time of 93 intrafamilial skin allografts performed under conditions of main histocompatibility complex (HLA) haploidentity with donor-recipient compatibility for products of the HLA-A, -B, -C, and - DR, as well as C3 proactivator, Glyoxalase I, and P loci located on the human 6th chromosome. Incompatibilities for HLA- A and -B (and to a lesser extent for HLA-C) and(or) for HLA-DR products exerted a strong influence upon the fate of skin allografts. When HLA-A and -B were considered alone, the most compatible group of grafts had a mean survival time of 15.8 d, as compared with 11.3 d for the most incompatible transplants. HLA-DR compatibility alone was associated with a mean survival time of 15.3 d, whereas HLA-DR-incompatible grafts had a mean survival time of 11.5 d. Incompatibilities for C3 proactivator, Glyoxalase I, and P did not have a significant effect upon graft survival. There was no evidence of an association between donor-recipient incompatibility at HLA-A, -B, or -C or at HLA-DR; such incompatibilities occurred independently of each other, in spite of the state of linkage disequilibrium known to exist between HLA-B and -DR. Incompatibilities for HLA-A, -B, and for HLA-DR exerted a potent additive effect upon graft survival. Skin grafts bearing one, two, or three incompatibilities had a mean survival time of 16.2, 13.7, and 10.7 d, […] Find the latest version: https://jci.me/109389/pdf Role of Ia-Like Products of the Main Histocompatibility Complex in Conditioning Skin Allograft Survival in Man J. DAUSSET, L. CONTU, L. LEGRAND, A. MARCELLI-BARGE, T. MEO, and F. T. RAPAPORT, Research Unit on Human Transplantation and Immunogenetics, Institut National de la Sante et de la Recherche Medicale, Unit 93, H6pital Saint-Louis, Paris 75010, France, and Department of Surgery, State University of New York at Stony Brook, Stony Brook, New York 11794 A B S T R A C T This report correlates the survival time techniques for the detection of donor-recipient com- of 93 intrafamilial skin allografts performed under patibility for HLA-DR. conditions of main histocompatibility complex (HLA) haploidentity with donor-recipient compatibility for INTRODUCTION products of the HLA-A, -B, -C, and -DR, as well as C3 proactivator, Glyoxalase I, and P loci located The influence of the main histocompatibility complex on the human 6th chromosome. Incompatibilities for (HLA)l allogenic differences on the fate of human skin HLA-A and -B (and to a lesser extent for HLA-C) and(or) grafts was established independently by Dausset et al. for HLA-DR products exerted a strong influence upon (1) and van Rood et al. (2) in 1965, in studies performed the fate of skin allografts. When HLA-A and -B were with preimmunized recipients. Subsequent intra- considered alone, the most compatible group of grafts familial skin grafting studies under conditions of had a mean survival time of 15.8 d, as compared with ABO-compatibility were performed (3, 4). Skin allo- 11.3 d for the most incompatible transplants. HLA-DR grafts exchanged by HLA-identical siblings were compatibility alone was associated with a mean accorded particularly prolonged survival times (5, 6). survival time of 15.3 d, whereas HLA-DR-incompatible Further detailed studies of the individual roles of grafts had a mean survival time of 11.5 d. Incompatibilities HLA-A and -B incompatibilities in skin allograft for C3 proactivator, Glyoxalase I, and P did not have a rejection were performed in a series of families of significant effect upon graft survival. known HLA genotypes (7, 8). For this purpose, 238 There was no evidence of an association between skin grafts were performed under conditions of donor- donor-recipient incompatibility at HLA-A, -B, or -C or recipient HLA haploidentity. Such allografts were at HLA-DR; such incompatibilities occurred inde- exchanged between parents and siblings, and occasion- pendently of each other, in spite of the state of ally between pairs of siblings in the volunteer families linkage disequilibrium known to exist between HLA-B available to the study since 1969 (7, 8). and -DR. Incompatibilities for HLA-A, -B, and for Subsequent progress in the immunogenetics of the HLA-DR exerted a potent additive effect upon graft HLA complex has resulted in the accumulation of a survival. Skin grafts bearing one, two, or three considerable array of new data regarding the occurrence incompatibilities had a mean survival time of 16.2, of additional markers of the HLA complex in the same 13.7, and 10.7 d, respectively (P < 0.0005). family units. During the past 8 yr, such families have The results point to the important role played by the been typed for human Ia-like determinants (the Ly-Li Ia-like products of the HLA complex (HLA-DR) in system, now termed HLA-DR) (9-11) as well as for conditioning skin allograft survival in man. This HLA-C, C3 proactivator (Bf) (12), and C2 (13). Data consideration may be of direct relevance to the have also been obtained on other markers present on potential clinical usefulness of in vitro serological IAbbreviations used in this paper: Bf, C3 proactivator; GLO, glyoxalase I; HLA, main histocompatibility complex; Receivedfor publication 26June 1978 and in revisedform 6 MLC, mixed lymphocyte culture; MST, mean survival time; November 1978. t, Student's t test. J. Clin. Invest. (© The American Society for Clinical Investigation, Inc. * 0021-9738/79/05/0893/09 $1.00 893 Volume 63 May 1979 893-901 TABLE I Data on 77 Haploidentical Skin Grafts Donors Recipients Nonshared haplotype Nonshared haplotype Shared haplotype Survival Sex DR B C A DR B C A t)R B C A timne d M 1* 35 4 26 xt 8 1 4 49 7 3 6.0 F 7 14 X§ 26 5 27 2 11 4 7 2 24 7.0 F 5 15 3 2 2 37 7 1 7 18 X 25 7.0 M 4 5 7 26 X 18 X 24 5 27 1 32 8.0 M X 35 4 24 X 37 X 1 6 14 x x 8.0 M X 27 1 1 4 27 2 11 5 44 1 2 8.0 M 7 44 X 29 5 7 X 24 3 8 X 1 8.0 F X 39 X 2 2 44 5 11 X 18 X 2 8.0 F 5 40 7 44 5 2 X 52 X 28 8.0 M 5 40 2 X X 52 X 28 7 44 5 2 8.5 M 5 35 X 3 5 49 X 24 3 X 4 1 9.0 F 5 51 1 2 X 8 X 30 X 18 X 3 9.0 M 7 44 X 29 5 27 1 32 X 18 X 24 9.0 F 6 35 4 3 5 40 X 2 2 52 X 24 9.0 F 6 15 3 28 3 X X 11 X 14 X 3 9.0 M 5 12 5 28 3 X X 11 X 14 X 3 9.0 Mil 5 12 5 28 6 15 3 28 X 14 X 3 9.0 M 2 12 3 x X 17 X 9 3 X X 11 9.0 M 6 35 4 2 5 27 2 11 4 7 2 24 9.0 F 6 35 4 2 4 7 2 24 5 27 2 11 9.0 M 5 35 x 3 3 X X 1 5 49 4 23 10.0 M 1 7 X 29 X 45 5 X 5 15.1 2 2 10.0 F 5 12 5 X X 14 X 3 3 X X 11 10.0 M 2 37 4 26 7 44 5 2 X 52 X 28 10.0 M 2 7 X 2 4 14 X 32 7 44 X 23 10.0 F 2 7 X 2 7 44 X 23 4 14 X 32 10.0 F 6 18 X 2 4 14 X 32 7 44 X 23 10.0 F 2 7 X 3 3 8 X 26 X 18 7 32 10.0 F 5 7 X 24 7 44 X 29 3 8 X 1 10.0 Mif 4 14 X 32 6 18 X 2 7 44 X 23 10.0 M X 35 7 32 7 44 X 23 3 8 4 1 10.0 M 4 27 X 26 X 45 X 29 7 27 2 3 10.0 M 5 X X 2 2 37 7 1 7 18 X 25 10.0 F 3 8 1 2 7 X 2 6 35 4 3 10.0 M 3 44 5 2 2 7 X 24 4 18 X 3 10.5 M 3 8 6 35 4 3 6 7 X 2 10.5 Mil X 18 24 4 51 7 26 5 27 1 32 11.0 M 1 27 1 2 5 14 X 28 7 13 7 30 11.0 M 4 27 2 24 2 44 X 24 X 7 X 26 11.0 F 3 15 3 11 X 13 7 30 5 7 X 24 11.0 894 Dausset, Contu, Legrand, Marcelli-Barge, Meo, and Rapaport TABLE I (Continued) Donors Recipients Nonshared haplotype Nonshared haplotype Shared haplotype Survival Sex DR B C A DR B C A DR B C A time d M 4 14 X 11 5 40 X 2 2 52 X 24 11.0 F 1 27 1 2 7 13 7 30 5 14 X 28 11.0 M 1 5 X 2 X 22 1 2 5 15.1 3 2 11.5 M 1 5 X 2 5 15.1 3 2 X 22 1 2 11.5 M X 18 5 30 3 8 X 26 5 18 7 32 12.0 F 3 18 5 30 5 15.2 3 32 7 17 X 2 12.0 F 5 44 4 2 3 8 4 1 7 44 4 23 12.0 F 3 38 X 26 2 51 7 2 6 35 4 28 12.0 F 1 35 4 2 4 40 3 28 2 7 X 1 12.5 M 5 41 X 26 5 35 4 32 3 41 X 32 13.0 F 2 51 X 2 X 7 X 26 2 44 X 24 13.0 F 6 51 2 2 X 13 7 30 5 7 X 24 13.0 Mil 5 13 7 30 7 14 X 28 1 27 1 2 14.0 F 1 15.1 3 2 5 15.1 3 2 X 22 1 2 14.0 M X 40 3 2 4 50 X 2 x x 5 23 14.0 M 2 8 X 1 2 35 4 X 5 18 X 24 15.0 M 5 8 X 1 6 40 X 32 X 8 X 1 15.0 F 5 8 X 1 X 8 X 1 6 40 X 32 15.0 M 5 41 X 26 3 41 X 32 5 35 4 32 15.0 M 3 8 X 2 5 14 X 31 5 40 3 25 15.5 M X 40 3 30 X 44 2 2 6 35 4 3 16.0 F X 8 X 2 6 35 4 28 2 51 7 2 16.5 Mil 7 14 X 28 7 13 7 30 1 27 1 2 16.5 M 7 44 X 29 7 37 4 1 6 35 X 3 17.0 F 5 51 3 24 7 39 X 24 X 51 X 31 17.0 M 4 40 3 28 6 35 4 2 2 7 X 1 17.0 M 3 44 X 23 4 22.1 3 11 1 35 4 1 17.5 F 6 15 3 28 2 44 5 28 X 14 X 3 17.5 F 2 7 X 11 7 17 X 2 5 15 3 32 17.5 F 5 8 X 1 6 8 X 1 6 7 X 3 18.0 M X 50 X 2 X 5 3 24 1 35 4 2 18.0 F 5 38 X 26 5 49 X 23 5 14 5 3 19.0 F X 22.1 1 11 5 49 X 30 2 7 x 24 20.0 F 7 45 4 23 X 51 X 31 7 39 X 24 20.0 M 2 8 7 1 X 51 7 29 6 45 x 1 23.0 M 6 18 3 1 6 45 3 1 X 51 7 29 23.0 F X 15 X 26 6 35 X 1 X 15 7 23 29.0 * The incompatibilities are indicated by antigens underlined.