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Adhesion molecule polymorphism
Abstracts
169
B-8.1 #221
ADHESION MOLECULE POLYMORPHISM. E Behar, D. Hiraki, S. Krishnaswamy, FC Grumet. Department of Pathology, Stanford University, Stanford, CA. Although a l l e l i c differences at MHC loci is a major element of graft rejection, polymorphism of other cell surface antigens probably also contribute to failure of engraftment. Because endothelial cells are among the f i r s t components of an allograft that are encountered by a host immune system, we decided to study possible polymorphisms of a prominent endothelial cell adhesion molecule, CD31. The published sequences of CD31 suggested amino acid differences in the 4th extracellular protein domain. A method similar to that used for direct DR genomic sequencing on an A.L.F. (Pharmacia) automated sequencer was used to sequence cDNA from endothelial cells of 10 different unrelated individuals. The expected polymorphism at positions 1206 and 1253 were not confirmed. Because the region involved was d i f f i c u l t to sequence, we believe that sequencing errors in the prior studies explain the suspected polymorphism. Preliminary analysis of our data does, however, suggest possible heterozygosity at positions 1172 and 1284-5. Additional invidividuals will be tested, as will clones derived from the putative heterozgygotes, to confirm and extend these findings.
C-8.2 #222
SPECIFIC IMMUNE DYSFUNCTION IN RECURRENT SPONTANEOUS ABORTION, EXTREME HIGH CTI.p FREQUENCIES, LACK OF SERUM BLOCKING IgG, SHARED TLX/MCP/CD46 PHENOTYPES. B Kotlan, A. Padanyi, GyG Petr,~nyi, E Gy6di, M Szigetv~ri, National Institute of Haematology, Blood Transfusion and Immunology, Budapest, Hungary Significant proportion of recurrent spontaneous abortion (RSA) is suggested to have immunological cause. Preliminary studies revealed that RSA paralleled in contrast to normal pregnancy with the absence of Fc-gamma-RII blocking antibody production and shared allotypes in the TLX/MCP/CD46 polymorphism*. Recent studies revealed that Fc-gamma-RII blocking IgG antibody is associated with allospecificity against TLX/MCP/CD46 polymorphic determinants. Couples suffering from RSA in comparison to healthy ones, are matching in TLX/MCP/CD46 allotypes missing the immunogeneic stimuli for "blocking" antibody production. Concerning in vivo cell mediated reactivity against partner target cells an extremely high CTLp was found in all RSA patients. MLC stimulated with partner lymphocytes displayed, too, high reactivity. It is suggested that failure to produce Fc-gamma-RII blocking IgG antibody together with induction of a strong CTLp response against partner cells are part of the pathogenic background of RSA. Normal pregnancy on the other hand, could be characterized by low, i. e. normal, level of CTLp and high Fc-gamma-RII blocking antibody titer. The possible contribution of TLX/MCP/CD46 and HLA alloantigens for the induction of suppressive regulation in normal pregnancy and the failure of it in RSA is discussed here. *Pad~nyi et al.: 11th HLA Workshop and Conference, Yokohama, 1991, pp. 236, (abstr)
169
B-8.1 #221
ADHESION MOLECULE POLYMORPHISM. E Behar, D. Hiraki, S. Krishnaswamy, FC Grumet. Department of Pathology, Stanford University, Stanford, CA. Although a l l e l i c differences at MHC loci is a major element of graft rejection, polymorphism of other cell surface antigens probably also contribute to failure of engraftment. Because endothelial cells are among the f i r s t components of an allograft that are encountered by a host immune system, we decided to study possible polymorphisms of a prominent endothelial cell adhesion molecule, CD31. The published sequences of CD31 suggested amino acid differences in the 4th extracellular protein domain. A method similar to that used for direct DR genomic sequencing on an A.L.F. (Pharmacia) automated sequencer was used to sequence cDNA from endothelial cells of 10 different unrelated individuals. The expected polymorphism at positions 1206 and 1253 were not confirmed. Because the region involved was d i f f i c u l t to sequence, we believe that sequencing errors in the prior studies explain the suspected polymorphism. Preliminary analysis of our data does, however, suggest possible heterozygosity at positions 1172 and 1284-5. Additional invidividuals will be tested, as will clones derived from the putative heterozgygotes, to confirm and extend these findings.
C-8.2 #222
SPECIFIC IMMUNE DYSFUNCTION IN RECURRENT SPONTANEOUS ABORTION, EXTREME HIGH CTI.p FREQUENCIES, LACK OF SERUM BLOCKING IgG, SHARED TLX/MCP/CD46 PHENOTYPES. B Kotlan, A. Padanyi, GyG Petr,~nyi, E Gy6di, M Szigetv~ri, National Institute of Haematology, Blood Transfusion and Immunology, Budapest, Hungary Significant proportion of recurrent spontaneous abortion (RSA) is suggested to have immunological cause. Preliminary studies revealed that RSA paralleled in contrast to normal pregnancy with the absence of Fc-gamma-RII blocking antibody production and shared allotypes in the TLX/MCP/CD46 polymorphism*. Recent studies revealed that Fc-gamma-RII blocking IgG antibody is associated with allospecificity against TLX/MCP/CD46 polymorphic determinants. Couples suffering from RSA in comparison to healthy ones, are matching in TLX/MCP/CD46 allotypes missing the immunogeneic stimuli for "blocking" antibody production. Concerning in vivo cell mediated reactivity against partner target cells an extremely high CTLp was found in all RSA patients. MLC stimulated with partner lymphocytes displayed, too, high reactivity. It is suggested that failure to produce Fc-gamma-RII blocking IgG antibody together with induction of a strong CTLp response against partner cells are part of the pathogenic background of RSA. Normal pregnancy on the other hand, could be characterized by low, i. e. normal, level of CTLp and high Fc-gamma-RII blocking antibody titer. The possible contribution of TLX/MCP/CD46 and HLA alloantigens for the induction of suppressive regulation in normal pregnancy and the failure of it in RSA is discussed here. *Pad~nyi et al.: 11th HLA Workshop and Conference, Yokohama, 1991, pp. 236, (abstr)