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6.3-01 Genetic predisposition to autoimmunity: Platelet and endothelial cell antibodies and nephritis
58
6.2-16
Abstract!
HLA DRw52”a” AND RFLP-SUBTYPING IN MOTHERS ALLOIMMUNIZED AGAINST PLA1 PLATELET ANTIGEN. N. Valentin*, A. Vergracht*, J.D. Bignon*, M.L. Cheneau*, C. Kaplan**, J.Y. Muller* * C.R.T.S. I-ILA - Allee Charles MiralliC - 44011 NANTES - FRANCE ** I.N.T.S. 6, rue A. Cabanel- 75015 PARIS - FRANCE Alloimmunisation against the PLAl antigen, responsible for neonatal alloimmune thrombocytopenia and post-transfusional purpura, is known to be associated with a HLA class II structure. Most of the immunized women have first been shown to possessthe DR3 specificity and subsequently the DRw52 supertypical specificity. Since DRw52 is known to be polymorphic (DRw-52”a”, -52”b”, -52”~” were cellularly defined and confiid by oligotyping) 18 immunised mothers (anti-PL* 1 immunisation) previously serologicaly typed were studied by RFLP analysis with TaqI, Eco RI, Bam HI, restriction enzymes and HLA DR beta-DQ alpha and DQ beta probes. According to the results of the Xth Histocompatibility Workshop, 16 cells were typed DR3-DQw2 (15 DRwl7 and one DRwl8). The two DRw6 were confirmed as DRw 13-DQw6. Surprisingly, all women had the DRw52a subtype specificity. Indeed all DNAs displayed characteristic DRw52a DRB pattern : presence of 9.79 kb Taq I and absence of 4,71 kb Eco RI bands, when DRw52c showed these two bands. Conversingly, DRw52b laked these two bands but displayed a 11.48 kb Taq I-DRl3 band. This finding strongly suggests that the DRB3 chain coding for DRw52 specificity is directly involved in the presentation of the PLAl antigen to the T-cells. In addition, the similarities between DR3 and DRw52 structures due to an hypothetical gene conversion event should be considered in order to explain the high frequency of DR3 among the DRw52a responding women. Alternatively, this increased frequency of DR3 might be due to the high response status associated with that specificity.
6.3-01 GENETIC
PREDfSPOSlTlCN TO AUTOMMUNITY: PLATELET AND ENDOTHELIAL CELL ANPIBODtES AND NEPHRITIS. S Has&@ (l), J Drouin (2), E Trudel (l), R Couture (2), D Page (2). Canadian Red Cross (1) and Ottawa Generai Hospital, University of Ottawa (2), Ottawa, Ontario. We have identified a family with several members expressing tllA antigens that are linked to autoimmuntty: Class I antigens Al. 58 and Class II antigens DFt3 and DR8. Two sisters developed nephritis following pregnancy and became dialysis dependent. Patient DM delivered a severely VlKHnbocytopenit child who suffered an intracranial bleed from which he mcover@. She later received a cadaver kidney allograft and fottowiq a severe episode of graft rejection, achieved sat&factory renal function wtth immunosuppmssive drugs. In a Western blot anafysis, her serum showed a potent alfoantfbody with PlAl positive pfatefets only; her pfatelets were PlAl negative. An IgG antibody to a surface 75 kD protein was aleo found in her serum using endothetfal cell lye&es in a Western blot assay. Serum of her sister (FC) also cont@ed an antibody to this 75 kD protein as well as to a 115 kD platelet protein comsepondii to glycopmtefn (GP) Ilta. An autoantibody to GP tlla was also found in the serum of their mother and of 2 asyfr@em& sisters. One of the latter also had an anticaM@in afMfMdy in her serum. The daughter of FC(tC), who had never been trane%& or pregnant showed an lgG anttbody to a 80 kD platetet me&uane proirrin ln her serum. The antikrdler datadid in these family members have played a role in the devskpment of the neonatal purpura. nephrftis and renal graft transpl&tation as well as in platelet transfusion.
6.2-16
Abstract!
HLA DRw52”a” AND RFLP-SUBTYPING IN MOTHERS ALLOIMMUNIZED AGAINST PLA1 PLATELET ANTIGEN. N. Valentin*, A. Vergracht*, J.D. Bignon*, M.L. Cheneau*, C. Kaplan**, J.Y. Muller* * C.R.T.S. I-ILA - Allee Charles MiralliC - 44011 NANTES - FRANCE ** I.N.T.S. 6, rue A. Cabanel- 75015 PARIS - FRANCE Alloimmunisation against the PLAl antigen, responsible for neonatal alloimmune thrombocytopenia and post-transfusional purpura, is known to be associated with a HLA class II structure. Most of the immunized women have first been shown to possessthe DR3 specificity and subsequently the DRw52 supertypical specificity. Since DRw52 is known to be polymorphic (DRw-52”a”, -52”b”, -52”~” were cellularly defined and confiid by oligotyping) 18 immunised mothers (anti-PL* 1 immunisation) previously serologicaly typed were studied by RFLP analysis with TaqI, Eco RI, Bam HI, restriction enzymes and HLA DR beta-DQ alpha and DQ beta probes. According to the results of the Xth Histocompatibility Workshop, 16 cells were typed DR3-DQw2 (15 DRwl7 and one DRwl8). The two DRw6 were confirmed as DRw 13-DQw6. Surprisingly, all women had the DRw52a subtype specificity. Indeed all DNAs displayed characteristic DRw52a DRB pattern : presence of 9.79 kb Taq I and absence of 4,71 kb Eco RI bands, when DRw52c showed these two bands. Conversingly, DRw52b laked these two bands but displayed a 11.48 kb Taq I-DRl3 band. This finding strongly suggests that the DRB3 chain coding for DRw52 specificity is directly involved in the presentation of the PLAl antigen to the T-cells. In addition, the similarities between DR3 and DRw52 structures due to an hypothetical gene conversion event should be considered in order to explain the high frequency of DR3 among the DRw52a responding women. Alternatively, this increased frequency of DR3 might be due to the high response status associated with that specificity.
6.3-01 GENETIC
PREDfSPOSlTlCN TO AUTOMMUNITY: PLATELET AND ENDOTHELIAL CELL ANPIBODtES AND NEPHRITIS. S Has&@ (l), J Drouin (2), E Trudel (l), R Couture (2), D Page (2). Canadian Red Cross (1) and Ottawa Generai Hospital, University of Ottawa (2), Ottawa, Ontario. We have identified a family with several members expressing tllA antigens that are linked to autoimmuntty: Class I antigens Al. 58 and Class II antigens DFt3 and DR8. Two sisters developed nephritis following pregnancy and became dialysis dependent. Patient DM delivered a severely VlKHnbocytopenit child who suffered an intracranial bleed from which he mcover@. She later received a cadaver kidney allograft and fottowiq a severe episode of graft rejection, achieved sat&factory renal function wtth immunosuppmssive drugs. In a Western blot anafysis, her serum showed a potent alfoantfbody with PlAl positive pfatefets only; her pfatelets were PlAl negative. An IgG antibody to a surface 75 kD protein was aleo found in her serum using endothetfal cell lye&es in a Western blot assay. Serum of her sister (FC) also cont@ed an antibody to this 75 kD protein as well as to a 115 kD platelet protein comsepondii to glycopmtefn (GP) Ilta. An autoantibody to GP tlla was also found in the serum of their mother and of 2 asyfr@em& sisters. One of the latter also had an anticaM@in afMfMdy in her serum. The daughter of FC(tC), who had never been trane%& or pregnant showed an lgG anttbody to a 80 kD platetet me&uane proirrin ln her serum. The antikrdler datadid in these family members have played a role in the devskpment of the neonatal purpura. nephrftis and renal graft transpl&tation as well as in platelet transfusion.