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Immunogenic system (HLA) and coronary atherosclerosis
Abstracts
P195
HLA
~D
VILIUISK ENCEPHALITIS
Fefelova Vera, Institute of Northern Medical Problems,
Krasnoyarsk, Russia Viliuisk encephalitis (VE) is a severe chronic disease of the central nervous system, which is met only in East Siberia (in Yakutia) in Mongoloids Yakuts. The etyology and pathogenesis of VE are unknown. 950 inhabitants of 18 settlements were examined. There is no difference in HLA antigens distribution in the most affected viliuisk region, in comparision with the other regions of Yakutia, where this disease is not met. 60. patients were examined. HLA-BI5 frequency was significantly increased in VE patients (63,3%) in comparision with the control (36,7%). The relative risk is 2,9. The author's hypothesis is suggested that the pathogenetic course of VE and possibly other diseases associated with HLA may be similar to a chronic transplantation conflict.
P197 HLA CLASS II AND TNFo; PROMOTORALLELES IN IGA DEFICIENCY Reil Angelika,Bein Gregor and Seyfarth Michael Institute of Immunology and Transfusion Medicine, University of Luebeck, Germany IgA deficiency (lgA-D) is the most common immunodeficiency, characterized by an arrest in B cell differentiation. Previous studies gave evidence for positive associations of IgA-D with particular HLA-DR-DO haplotypes. To confirm this association 20 IgA deficient (serum IgA < 0.05 gil) individuals were typed for HLA-DR and DO alleles using gene amplification and hybridization with sequence-specific oligonucleotide probes. Furthermore they were typed for 2 TNFa. promotor alleles using restrictionfragment length polymorphism analysis. 111 healthy blood donors were used as controls. We found strong positive associations with DOB1'02 and '0501. Phenotype frequencies (pI) were 0.85 comparedwith 0.306 in controlsfor '02 (p -c0.001) and 0.45 I 0.218 for '0501 (p < 0.05). DOB1'0602 was strong negative associated with IgA-D (pf:O.O I 0.279; P -c 0.05). In accordancewith the well established linkage disequilibrium we found positive associations of IgA-D with DRB1'03011 (pf: 0.50 I 0.17; P -c 0.01), '0701 (pf: 0.40 I 0.24; n. s.) and '01 alleles (pf: 0.40 I 0.19; n. s.). DRBI 'IS alleles were negative associatd with IgA-D (pf: 0.0 I 0.30; P -c 0.01). Gene frequencies (gf) of TNFa. 1 and TNFo; 2 were 0.65 and 0.35 in igA-D compared with 0.86 and 0.14 in controls (p < 0.001). The higher gene frequency of TNFo; 2 in IgA-D might be expiainedby its linkage to DRBI '03011, which is more frequent in the IgA-D group. We confirm the hypothesis that HLA class II molecules themselves might be involved in the pathogenesis of IgA-D.
P199
HLA ANTIGENS AND HEARTFAILUREIN ~.THALASSEMIA MAJOR M.Spyropoulou-Vlachou', P.Flevaris',E.Vrettou', D.Tsiapras', D.Kremastinos', C.Stayropoulos-Giokas', 'Departmentof Immunology and nationalTypingCenter, GeneralHospitaiof Athens"G.Gennimatas· and 'Departmentof Cardiology, OnassisCardiacSurgeryCenter. Congestive heartlailure is the main causeof death in patientswith p-thalassemia major(p-Thal). An autoimmune processhas recentlybeen implicated in this type of heart failure (HF) which is associated with left venticular systolicdysfunction. The aim of this study was to investigate whether HLA antigens, apart from multiple transfusions and iron loading, are associated with left-sided, dilated type cardiomyopathy observed in homozygous Il-ThaI. For this purpose two groups of patients were studied: (a) 42 unrelated Greek patients with Il-Thai and HF (mean feritin 3052±1475, echocardiographic shortening fraction 19±7)and (b) 42 age and sex matched unrelated p-Thal patients without HF (mean feritn 3260±12BO), while 130 healthy unrelated Greek servedas controls. HLA class I A, Band HLA class II DRB1' typing was performed by using CDC assay and peR-SSO respectively. A statisticallysignificantlowerfrequencyof the DRB1' allele was found among HF pts compared to thalassemic pts without HF (><'=7.3, p=0,007) and, also, to healthy controls(x'=10.1, p=0,002). Thesefindingssuggestthat BRB1'14 allelemay play a protectiverole againstthe development of HF in Il-Thai and supportthe hypothesis that, apart from multiple transfusions and iron loading, immunogenetic factors are
also involvedin the pathogenesis of HF in Il-ThaI.
39
P196 HLA SEGREGATION IN MULTlCASE NARCOLEPSY FAMILIES Lattermann A. 1), Mayer G.2), S11(anborg E.3), Meier-Ewert K. 2), Mlgnot E.'+), Mueller-Eckhardt G. I) Glessen ) Germany 1) , Schwalmstadt, Germany2), Stockholm, Sweden 3 Palo Alto, USA4) Narcolepsy is the disease with the strongest HLA association. However, multicase families are very rare. Segregation analysis was performed in 4 European families. A total of 10 narcolepsy patients fu~illing the criteria of the Stanford Sleep Inventory, and 37 healthy individuals were typed for HLA class I by serology, for class II alleles and DOCAR from genomic DNA. In 3 families all patients carry the expected DRB1*1501/DOB1*0602 haplotype, but not always in a genotypically identical form. Eight healthy family members share this haplotype with their narcoleptic relatives. In a fourth family, the DR2-negative diseased father and his narcoleptic daughter have a DRB1*1302/ DOB1*0604 haplotype in common, while she inherits DRB1*1501/DOB1*0602 from her healthy mother. As a result, dominant transmission of the disease with incomplete penetrance seems most likely in 3 of 4 families. However, no clear linkage pattern with HLA can be deduced which would be common to all families investigated. This underlines a multifactorial mode of inheritance of narcolepsy.
P198
HIGHFREOUENCY OF HLA,-A33,-B14.-ORI IN SELECTIVE IgA OEFICIENCY AND COMMON VARIABLE IMMUNODEFICIENCY DespinaChryssovergi, HelenPappas, KaterinaTarassi, TheophilosAthanasiadis, loanna Economidou, Chryssa Papasteriades. Immunology - Histocompatibility Department, EvangeJismos Hospital, Athens- Greece.
Common variable immunodeflciency (CVI-D) andselective IgAdeficiency (lgAD) are primary immunodeficiencies characterized by impaired antibody production.
Despite the fact that many immunologic and chromosomal studies have been performed to elucidate these deficiencies, no simple causes and few genetic associations have been determined.
The aim of this study was to investigate the possible HLA associations in
CVI-O and IgA-D in a Greek population. For this purpose we serotyped for all known HLA class I and class II antigens the following groups of subjects. a) 12 patients (5 males and 7 femaies) with CVI-O. b) 12 patients (3 males and9 females) w~h IgA-D. c) 105 healthy subjects (55 males and 50 females) as controls. In comparison to the control group the results have as follows: a) The CVI-D
patients presented with a higher frequency of HLA-A33 (25% vs 4.76%, RR~6.66, x'·4.112, p
A33 B14 (41.66% vs 0.4%, x'-28.52, p<0.OO1), and HLA-B14 OR1 (40.0% vs 0.4%, x'-22.04, p<0.OO1}. tn conclusion, the HLA-antigens may contribute directly to the pathogenesis of CVI-D and IgA-D or they may appear as markers for the possible genetic defect. The fact that the same HLA antigens associations were found in both CVI-D and IgAo may indicate that these abnormalities of the humoral immunity probably share the same genetic background.
P200
1Il!l.1tKXElICS'lsiHI IHLA)
AIID CU
A~IS
L. D. serova. R.P. I1anlstiUna. S. H. MaKsiJllov, H.A Gratz1arulKY Instltute Of cunicar and ExPeriJrental InmmolOllY.
Moscow, Russla InteITelatlOll between
auercscterosis
the HLA system and coronary (CAl was determ.i.ned fOr patients 1n the
YOIlIl8 aile IlrOUP (35-42 years Of agel.
armseres
At the POPUlatlOll
of B and DR reaicos 1n patients were:Bl5-16, 61. (RR=2. 21. 6=0.09l. B35-21.11. IRR= 1. 12. 6=0.09l. IJRi!-45.61. (RR=2. 04. 6=0. (4). DR5-5'l.31. IRR=3.29. 6=0. 31l. as COIIPared correSPOlldinllly to 8,11.. 16. '11.. 26. 61.. 29. 11. m the controi llI'OOP. Strenllth of aascctauve 1iJj<;s between CA and B35.11R5 anttseres accordiIlll to the results Of famlly ararrsrs IS lIlleb nore eXPreSsed than m PatIents at the population level_ It was detem1ned 1n the PrOCess of stUdY that HLA Of haPlotype A9. B35.llR5 doollnated 1n PrObands and theIr fanH y JreIIlbers.
leve 1
P195
HLA
~D
VILIUISK ENCEPHALITIS
Fefelova Vera, Institute of Northern Medical Problems,
Krasnoyarsk, Russia Viliuisk encephalitis (VE) is a severe chronic disease of the central nervous system, which is met only in East Siberia (in Yakutia) in Mongoloids Yakuts. The etyology and pathogenesis of VE are unknown. 950 inhabitants of 18 settlements were examined. There is no difference in HLA antigens distribution in the most affected viliuisk region, in comparision with the other regions of Yakutia, where this disease is not met. 60. patients were examined. HLA-BI5 frequency was significantly increased in VE patients (63,3%) in comparision with the control (36,7%). The relative risk is 2,9. The author's hypothesis is suggested that the pathogenetic course of VE and possibly other diseases associated with HLA may be similar to a chronic transplantation conflict.
P197 HLA CLASS II AND TNFo; PROMOTORALLELES IN IGA DEFICIENCY Reil Angelika,Bein Gregor and Seyfarth Michael Institute of Immunology and Transfusion Medicine, University of Luebeck, Germany IgA deficiency (lgA-D) is the most common immunodeficiency, characterized by an arrest in B cell differentiation. Previous studies gave evidence for positive associations of IgA-D with particular HLA-DR-DO haplotypes. To confirm this association 20 IgA deficient (serum IgA < 0.05 gil) individuals were typed for HLA-DR and DO alleles using gene amplification and hybridization with sequence-specific oligonucleotide probes. Furthermore they were typed for 2 TNFa. promotor alleles using restrictionfragment length polymorphism analysis. 111 healthy blood donors were used as controls. We found strong positive associations with DOB1'02 and '0501. Phenotype frequencies (pI) were 0.85 comparedwith 0.306 in controlsfor '02 (p -c0.001) and 0.45 I 0.218 for '0501 (p < 0.05). DOB1'0602 was strong negative associated with IgA-D (pf:O.O I 0.279; P -c 0.05). In accordancewith the well established linkage disequilibrium we found positive associations of IgA-D with DRB1'03011 (pf: 0.50 I 0.17; P -c 0.01), '0701 (pf: 0.40 I 0.24; n. s.) and '01 alleles (pf: 0.40 I 0.19; n. s.). DRBI 'IS alleles were negative associatd with IgA-D (pf: 0.0 I 0.30; P -c 0.01). Gene frequencies (gf) of TNFa. 1 and TNFo; 2 were 0.65 and 0.35 in igA-D compared with 0.86 and 0.14 in controls (p < 0.001). The higher gene frequency of TNFo; 2 in IgA-D might be expiainedby its linkage to DRBI '03011, which is more frequent in the IgA-D group. We confirm the hypothesis that HLA class II molecules themselves might be involved in the pathogenesis of IgA-D.
P199
HLA ANTIGENS AND HEARTFAILUREIN ~.THALASSEMIA MAJOR M.Spyropoulou-Vlachou', P.Flevaris',E.Vrettou', D.Tsiapras', D.Kremastinos', C.Stayropoulos-Giokas', 'Departmentof Immunology and nationalTypingCenter, GeneralHospitaiof Athens"G.Gennimatas· and 'Departmentof Cardiology, OnassisCardiacSurgeryCenter. Congestive heartlailure is the main causeof death in patientswith p-thalassemia major(p-Thal). An autoimmune processhas recentlybeen implicated in this type of heart failure (HF) which is associated with left venticular systolicdysfunction. The aim of this study was to investigate whether HLA antigens, apart from multiple transfusions and iron loading, are associated with left-sided, dilated type cardiomyopathy observed in homozygous Il-ThaI. For this purpose two groups of patients were studied: (a) 42 unrelated Greek patients with Il-Thai and HF (mean feritin 3052±1475, echocardiographic shortening fraction 19±7)and (b) 42 age and sex matched unrelated p-Thal patients without HF (mean feritn 3260±12BO), while 130 healthy unrelated Greek servedas controls. HLA class I A, Band HLA class II DRB1' typing was performed by using CDC assay and peR-SSO respectively. A statisticallysignificantlowerfrequencyof the DRB1' allele was found among HF pts compared to thalassemic pts without HF (><'=7.3, p=0,007) and, also, to healthy controls(x'=10.1, p=0,002). Thesefindingssuggestthat BRB1'14 allelemay play a protectiverole againstthe development of HF in Il-Thai and supportthe hypothesis that, apart from multiple transfusions and iron loading, immunogenetic factors are
also involvedin the pathogenesis of HF in Il-ThaI.
39
P196 HLA SEGREGATION IN MULTlCASE NARCOLEPSY FAMILIES Lattermann A. 1), Mayer G.2), S11(anborg E.3), Meier-Ewert K. 2), Mlgnot E.'+), Mueller-Eckhardt G. I) Glessen ) Germany 1) , Schwalmstadt, Germany2), Stockholm, Sweden 3 Palo Alto, USA4) Narcolepsy is the disease with the strongest HLA association. However, multicase families are very rare. Segregation analysis was performed in 4 European families. A total of 10 narcolepsy patients fu~illing the criteria of the Stanford Sleep Inventory, and 37 healthy individuals were typed for HLA class I by serology, for class II alleles and DOCAR from genomic DNA. In 3 families all patients carry the expected DRB1*1501/DOB1*0602 haplotype, but not always in a genotypically identical form. Eight healthy family members share this haplotype with their narcoleptic relatives. In a fourth family, the DR2-negative diseased father and his narcoleptic daughter have a DRB1*1302/ DOB1*0604 haplotype in common, while she inherits DRB1*1501/DOB1*0602 from her healthy mother. As a result, dominant transmission of the disease with incomplete penetrance seems most likely in 3 of 4 families. However, no clear linkage pattern with HLA can be deduced which would be common to all families investigated. This underlines a multifactorial mode of inheritance of narcolepsy.
P198
HIGHFREOUENCY OF HLA,-A33,-B14.-ORI IN SELECTIVE IgA OEFICIENCY AND COMMON VARIABLE IMMUNODEFICIENCY DespinaChryssovergi, HelenPappas, KaterinaTarassi, TheophilosAthanasiadis, loanna Economidou, Chryssa Papasteriades. Immunology - Histocompatibility Department, EvangeJismos Hospital, Athens- Greece.
Common variable immunodeflciency (CVI-D) andselective IgAdeficiency (lgAD) are primary immunodeficiencies characterized by impaired antibody production.
Despite the fact that many immunologic and chromosomal studies have been performed to elucidate these deficiencies, no simple causes and few genetic associations have been determined.
The aim of this study was to investigate the possible HLA associations in
CVI-O and IgA-D in a Greek population. For this purpose we serotyped for all known HLA class I and class II antigens the following groups of subjects. a) 12 patients (5 males and 7 femaies) with CVI-O. b) 12 patients (3 males and9 females) w~h IgA-D. c) 105 healthy subjects (55 males and 50 females) as controls. In comparison to the control group the results have as follows: a) The CVI-D
patients presented with a higher frequency of HLA-A33 (25% vs 4.76%, RR~6.66, x'·4.112, p
A33 B14 (41.66% vs 0.4%, x'-28.52, p<0.OO1), and HLA-B14 OR1 (40.0% vs 0.4%, x'-22.04, p<0.OO1}. tn conclusion, the HLA-antigens may contribute directly to the pathogenesis of CVI-D and IgA-D or they may appear as markers for the possible genetic defect. The fact that the same HLA antigens associations were found in both CVI-D and IgAo may indicate that these abnormalities of the humoral immunity probably share the same genetic background.
P200
1Il!l.1tKXElICS'lsiHI IHLA)
AIID CU
A~IS
L. D. serova. R.P. I1anlstiUna. S. H. MaKsiJllov, H.A Gratz1arulKY Instltute Of cunicar and ExPeriJrental InmmolOllY.
Moscow, Russla InteITelatlOll between
auercscterosis
the HLA system and coronary (CAl was determ.i.ned fOr patients 1n the
YOIlIl8 aile IlrOUP (35-42 years Of agel.
armseres
At the POPUlatlOll
of B and DR reaicos 1n patients were:Bl5-16, 61. (RR=2. 21. 6=0.09l. B35-21.11. IRR= 1. 12. 6=0.09l. IJRi!-45.61. (RR=2. 04. 6=0. (4). DR5-5'l.31. IRR=3.29. 6=0. 31l. as COIIPared correSPOlldinllly to 8,11.. 16. '11.. 26. 61.. 29. 11. m the controi llI'OOP. Strenllth of aascctauve 1iJj<;s between CA and B35.11R5 anttseres accordiIlll to the results Of famlly ararrsrs IS lIlleb nore eXPreSsed than m PatIents at the population level_ It was detem1ned 1n the PrOCess of stUdY that HLA Of haPlotype A9. B35.llR5 doollnated 1n PrObands and theIr fanH y JreIIlbers.
leve 1